Journal of Medical Microbiology

Background The microbial aetiology of early childhood caries (ECC) in sub-Saharan African populations remains poorly characterised, with most studies focusing on conventional cariogenic pathogens like Streptococcus mutans. This study aimed to characterise the salivary microbial profile of children with ECC in urban Kano, northern Nigeria. Methods In this cross-sectional study of 162 children aged 3-5 years in urban Kano, unstimulated saliva samples were collected and analysed using standard bacteriological culture methods. Caries status was assessed using decayed, missing, and filled teeth (dmft) index and International Caries Detection and Assessment System (ICDAS). Microbial isolates were identified through Gram staining, colony morphology, and biochemical tests (catalase, coagulase, oxidase). Results Of 32 microbial isolates obtained, Staphylococcus aureus was the most prevalent (43.8%, n=14), followed by Streptococcus species (28.1%, n=9), Klebsiella species (12.5%, n=4), non-aureus staphylococci (6.3%, n=2), yeast (6.3%, n=2), and Pseudomonas species (3.1%, n=1). Only one isolate demonstrated direct association with dmft-detectable caries. Polymicrobial colonisation occurred in four cases (12.5%), predominantly featuring S. aureus-yeast combinations (n=2). White spot lesions (ICDAS 1-2) were associated with S. aureus and Klebsiella species in two separate cases. Conclusion This study reveals an unexpected predominance of S. aureus in the salivary microbiome of children in northern Nigeria, challenging conventional paradigms of ECC microbiology. The low correlation between microbial isolates and clinical caries suggests complex, multifactorial aetiology. These findings highlight the need for molecular characterisation of oral microbiomes in African populations and reconsideration of caries pathogenesis models in this unique epidemiological context.

In the past decade, dengue fever has emerged as a major public health on Reunion Island in the Southwest Indian Ocean. During the 2018-2022 outbreak, an unusual increase in ocular complications was reported in some patients. To investigate a potential viral cause, we analysed 447 blood samples from hospitalized patients with and without ophthalmic symptoms. Genetic sequencing revealed the co-circulation of two strains of dengue virus serotype 1, both genetically linked to strains previously identified in Asia. Notably, all patients with ophthalmic symptoms were infected with viruses from a single cluster within genotype I, which harbored several unique mutations. These findings suggest that the rare ocular complications observed during this outbreak may be associated with specific viral cluster. Further laboratory studies are required to confirm this potential link.

Aim and ObjectivesThe study aimed to evaluate the effectiveness of titanium inserts for interdental papilla reconstruction, comparing it with the Han and Takei technique using subepithelial connective tissue grafts. The objectives included assessing the black triangle height, papilla height and papilla presence index (PPI) at baseline, 1 month and 3 months postoperatively along with the evaluation of Early Wound Healing Score (EHS) during the first week of post operative healing period. Patients and MethodsThis single-blind randomized clinical trial included systemically healthy individuals aged 18-35 years with Nordland and Tarnows Class I-III papillary loss. A total of 18 participants were randomly assigned to either test group or control group. Clinical parameters were measured pre- and post-operatively at specified intervals. Both groups received standard presurgical care and postoperative follow-up. The surgical protocol for the test group involved titanium insert placement in the interdental bone, while the control group received a connective tissue graft using the Han and Takei method. ResultsBoth groups showed significant intragroup improvements in all parameters from baseline to 1 and 3 months (p<0.05). However, intergroup comparisons showed no significant differences at most time points, except at 3 months for PPI, where the control group showed significantly better results (p=0.04). EHS scores were not significant between the groups. ConclusionTitanium inserts and CTG both demonstrated clinical effectiveness in enhancing interdental papilla dimensions. These findings support the titanium insert as a viable, less invasive alternative, offering clinicians a practical option for esthetic papilla reconstruction.

The rapid diagnosis of Campylobacter infections is important for the management of infectious gastroenteritis. Although stool culture is considered the gold standard, its sensitivity is limited and it requires prolonged incubation times. We performed a prospective multicenter study at nine healthcare facilities in Japan to evaluate a Campylobacter rapid antigen test using stool specimens between March 2024 and August 2025. Patients with suspected infectious gastroenteritis were consecutively enrolled and tested using QuickNavi-Campylobacter and compared with the FilmArray Gastrointestinal Panel as the reference method. Discordant results were further evaluated by culturing and additional PCR assays. In total, 410 patients were included in the final analysis. The positive, negative, and total concordance rates between QuickNavi-Campylobacter and FilmArray Gastrointestinal Panel were 79%, 99%, and 93%, respectively. The positive concordance rate decreased in specimens collected [&ge;] 6 days after the onset of symptoms (50%). QuickNavi-Campylobacter demonstrated relatively good concordance with the FilmArray Gastrointestinal Panel in a real-world multicenter setting. These results suggest that this rapid antigen test may be particularly useful for the early diagnosis of suspected campylobacteriosis.

Mycobacterium tuberculosis (MTB) disease is a major global health threat with most tuberculosis (TB) cases occurring in low-and middle-income countries (LMIC) with limited healthcare infrastructure. Near-point-of-care testing which can be deployed at peripheral clinical settings is needed to start treatment earlier and thereby improve treatment outcomes. Here we report the development and preliminary characterization of an MTB detection assay that utilizes tongue swab or sputum specimens for The DASH(R) Rapid PCR System which employs cartridge-based automated sequence specific capture sample prep combined with dual target qPCR multicopy MTB insertion sequences IS6110 and IS1081 amplification and detection. MTB is resistant to conventional bacterial lysis techniques; therefore, we evaluated two pre-cartridge lysing techniques, mechanical lysis and sonication, and selected sonication for all subsequent studies. The DASH MTB assay demonstrated a limit of detection of 2.5 MTB cells/swab with no detection of 10 non-tuberculosis Mycobacterium strains. Clinical testing of 100 (49 positive and 51 negative) de-identified blinded sputa from South African symptomatic clinic attendees yielded an overall test sensitivity of 96% (100% for smear positive samples and 88% for smear negative samples) and specificity of 88% when compared to sputum culture. In a separate study of 110 tongue swab specimens (70 positive and 40 negative) from South African symptomatic clinic attendees, the sensitivity was 93% and the specificity was 100%. We further demonstrated that the test is compatible with peripheral LMIC settings via external battery operation and cartridge stability at 45{degrees}C for up to one year. ImportanceTuberculosis (TB) is the single most deadly infectious disease with 1.23 million deaths in 2024. Near-point-of-care testing which can be deployed at peripheral settings that lack laboratory infrastructure to deliver prompt and accurate diagnosis is needed to start treatment earlier and thereby improve treatment outcomes. In this study, we have developed an automated test to detect Mycobacterium tuberculosis (MTB), the cause of TB, from sputum and tongue swab specimens. Its high sensitivity and specificity, rapid time to result, and compatibility with environments that lack air conditioning and consistent electricity make this assay suitable for diverse clinical settings.

BackgroundTalaromycosis, caused by the fungus Talaromyces marneffei, is a leading cause of HIV-associated death in Southeast Asia. Current culture-based diagnosis only identifies late-stage infection, limiting understanding of disease burden and disease spectrum. We evaluated the clinical performance of anti-Mp1p IgM and IgG enzyme immunoassays (EIA) for talaromycosis diagnosis. MethodsThis diagnostic study included 423 adults with advanced HIV disease and culture-confirmed talaromycosis as cases, and 206 non-talaromycosis individuals with and without HIV who have never traveled to Asia as controls. Anti-Mp1p IgM and IgG antibodies were measured using conventional double-sandwich EIA. Diagnostic performance was assessed using the healthy control group and the HIV control group separately. Assay cut-offs were based on both the Youden index generated from the receiver operating characteristic curves, and separately using a pre-defined specificity of 95%. ResultsAt the pre-defined 95% specificity, IgM had low to moderate accuracy of 62.3% and 87.9%, and a low sensitivity of 8.3% and 21.3%, when evaluated with healthy and HIV controls, respectively. IgG had similarly low accuracy of 52.2% and 78.4%, and a low sensitivity of 21.5% and 30.5%, when evaluated using healthy and HIV controls, respectively. Both IgM and IgG assays performed better in HIV controls than healthy controls. ConclusionsThe anti-Mp1p IgM and IgG EIAs show low utility for the diagnosis of acute talaromycosis. However, at the high specificity cut-off of 95%, the assays have utility in the detection of T. marneffei exposure at both individual and population levels, and. provides a foundation for future sero-epidemiological studies. IMPORTANCETalaromycosis, caused by the dimorphic fungus Talaromycosis marneffei endemic in Southeast Asia, southern China, and northeastern India, is an invasive fungal infection that causes over 25,000 cases and 6,000 deaths annually but remains neglected in the global health community. Current diagnosis requiring culture-based testing is too slow, often resulting in patient death before treatment can begin. This study presents the first large-scale clinical evaluation of antibody tests for talaromycosis. While the antibody tests showed limited sensitivity for diagnosing acute disease, the high specificity makes them useful in determining prior exposure to T. marneffei, providing a new tool for public health investigation of disease prevalence at a population level, and for clinicians to identify individuals at risk for disease reactivation who may benefit from prevention strategies. The research provides important groundwork for improving disease control efforts in regions where this neglected infection is endemic.

BackgroundCanine impaction represents one of the most challenging clinical scenarios in orthodontic practice, with maxillary canines being the second most commonly impacted teeth after third molars. The management of impacted canines through orthodontic traction requires an advanced understanding of biomechanical principles, surgical techniques, and patient-specific factors. The decision to attempt traction must be informed by accurate differentiation between mechanical impaction and primary failure of eruption (PFE), as applying orthodontic force to PFE teeth results in failure and iatrogenic ankylosis. Recent systematic synthesis of eruption disorders further underscores the need to differentiate mechanical impaction from genetically mediated eruption failure prior to orthodontic traction [59]. In a companion systematic review, we have synthesized the evidence on genetic etiology and diagnostic accuracy for PFE. The present review focuses specifically on the management of confirmed mechanical impaction requiring orthodontic traction, providing a complete evidence-based framework for clinicians. ObjectiveTo provide the most comprehensive quantitative synthesis to date of orthodontic traction for impacted canines, encompassing biomechanical principles, comparative outcomes of open versus closed surgical exposure techniques, radiographic predictors of traction duration, complications, innovations, and evidence-based clinical recommendations with a practical decision algorithm. MethodsA systematic search of PubMed/MEDLINE and the Cochrane Library was conducted for studies published between January 2000 and February 2026, supplemented by citation tracking in Google Scholar. The PRISMA 2020 guidelines were followed. The protocol was prospectively registered on the Open Science Framework (DOI: 10.17605/OSF.IO/3UDH6). Eligible studies included randomized controlled trials, prospective cohort studies, retrospective cohort studies with at least 20 patients, case-control studies, systematic reviews, and meta-analyses. Risk of bias was assessed using ROBINS-I, RoB 2.0, and ROBIS tools. Meta-analyses employed random-effects models with Hartung-Knapp adjustment. Heterogeneity was assessed using I-squared and tau-squared statistics. Prediction intervals were calculated for meta-analyses with substantial heterogeneity. The GRADE framework evaluated evidence quality. Given the predominance of observational studies, pooled estimates should be interpreted as associations rather than causal effects. ResultsFrom 3,587 records, 94 studies (9,156 patients) met inclusion criteria. Optimal force magnitudes range from 50-150g, with force direction determined by the center of resistance located halfway along the root length. Meta-analyses demonstrated comparable success rates between open (91%, 95% CI: 88-94%) and closed (93%, 95% CI: 89-95%) surgical exposure techniques (9 studies; 3 RCTs, 6 observational; tau-squared = 0.00). Open exposure was associated with reduced traction duration (mean difference -4.7 months, 95% CI: -7.3 to -2.1; I-squared = 87%, tau-squared = 5.82; prediction interval -9.8 to 0.4 months) and lower ankylosis risk (OR 0.15, 95% CI: 0.03-0.83; I-squared = 0%, tau-squared = 0.00). Closed exposure was associated with reduced postoperative pain (mean difference -1.9 VAS, 95% CI: -2.6 to -1.2; I-squared = 0%, tau-squared = 0.00). Radiographic predictors include alpha-angle (beta = 0.16 months/degree), d-distance (beta = 1.20 months/mm), and sector location. Three-dimensional analysis demonstrates that cusp tip displacement explains approximately 55.4% of variance in traction duration. Complications include root resorption (23-48% of adjacent incisors; pooled MD 0.69 mm, 95% CI: 0.58-0.80 mm), alveolar bone loss (pooled MD 0.51 mm, 95% CI: 0.31-0.72 mm), and ankylosis (3.5-14.5%). GRADE evidence quality ranged from high (postoperative pain) to very low (acceleration modalities). Innovations: temporary anchorage devices (moderate-high, established); digital workflows (moderate, emerging); clear aligner-based traction (low, experimental); low-level laser therapy (low-moderate, adjunct only); vibration devices (high-quality negative evidence, not recommended). ConclusionsThis most comprehensive quantitative synthesis demonstrates that both open and closed surgical exposure techniques yield excellent success rates. Open exposure offers advantages in reduced traction duration and lower ankylosis risk, while closed exposure provides superior patient comfort. Radiographic predictors enable accurate pretreatment estimation of treatment duration. The findings of this review, combined with our companion analysis of the genetic and diagnostic basis of PFE [59], support a paradigm shift toward a genetically informed and mechanistically driven approach to all forms of failed tooth eruption. A practical clinical decision algorithm is provided to guide evidence-based management.

BackgroundThe use of fluoride-containing dentifrices can reduce the risk of dental caries. The systematic review was conducted to address two research questions: (i) the prevalence and frequency of fluoridated toothpaste use among Nigerian children and adolescents across geographic and demographic settings, and (ii) its association with dental caries prevalence, stratified by location and baseline caries risk. MethodsThis systematic review, registered with PROSPERO (CRD42022362116), followed the PRISMA guidelines. A PIO framework was applied to include children and adolescents (6 months-19 years) in Nigeria using fluoridated toothpaste, with caries outcomes measured via dmft/DMFT indices. A comprehensive search of PubMed, Web of Science, Scopus, Embase, AJOL, and Google Scholar was conducted from January 2001 to January 2026, supplemented by reference and grey literature searches. Study selection, data extraction, and risk of bias assessment using an adapted Hoy et al. tool were performed independently by multiple reviewers, with high inter-rater reliability (Kappa=0.90). Data were pooled using a random-effects model, with sensitivity, subgroup, and meta-regression analyses conducted to explore heterogeneity and effect modifiers. Publication bias was assessed using funnel plots and Eggers test. ResultsOf 1,194 identified records, 18 studies (n=12,719 participants) were included. The use of fluoridated toothpaste was widespread (prevalence: 61.9% to 95.8%), yet its association with dental caries varied significantly by location. A meta-analysis of 14 studies indicated a significant 16% reduction in caries odds with fluoridated toothpaste use after removal of an influential outlier (OR = 0.84, 95% CI: 0.71-0.99, p=0.04). Subgroup analyses revealed this protective association was significant in urban and rural settings (p<0.05) but absent in suburban Nigeria. Furthermore, dental caries prevalence and severity (DMFT/dmft) were substantially higher in urban and rural areas, where the association was significant, compared to suburban regions. All studies were assessed as having a low risk of bias, and no significant publication bias was detected. ConclusionFluoridated toothpaste is widely used in Nigeria and associated with a reduction in the prevalence of dental caries in Nigeria. It appears the relationship is moderated by residential location, and the DMFT/dmft. Longitudinal studies are needed to explore the interactions between the DMFT/dmft, use of fluoridated toothpaste, and residential location in Nigeria.

BackgroundScalable, non-invasive markers for cognitive-decline risk are limited. Olfactory dysfunction is predictive, and oral dysbiosis is mechanistically linked to neurocognitive pathways. Hence, we tested whether pairing smell and global cognition with salivary microbiome profiling yields a targeted, clinically useful signal. MethodsWe enrolled 113 Memory Center attendees and community controls. Same-day MMSE, UPSIT, and saliva were obtained for 16S rRNA gene sequencing and cytokine measurement. Unsupervised k-means clustering on standardized MMSE-UPSIT defined two groups of participants: CNN (cognitively normal, normosmia) and CIH (cognitively impaired, hyposmia). Ordination and elastic-net models adjusted for age, sex, BMI, and sequencing depth. Functions were inferred with PICRUSt2 and were integrated with taxa via DIABLO. ResultsOverall, the 16S-based microbial community structure was similar between groups, indicating minor compositional shifts. CIH showed enrichment of periodontal anaerobes (Porphyromonas, Treponema and Prevotella), whereas CNN retained nitrate-reducing commensals (e.g. Neisseria subflava, Aggregatibacter aphrophilus). Functional shifts showed mixed consistency with literature, aligning for outer membrane usher proteins and alkyldihydroxy phosphate synthase, but diverging for thiaminase, alpha-glucuronidase, and chemotaxis protein CheX. Most salivary cytokines levels did not differ between groups. ConclusionsThis integrated smell, cognition, and saliva workflow delineates an olfactory- cognitive phenotype linked to a targeted, potentially modifiable salivary dysbiosis, periodontal anaerobes vs nitrate-reducers, rather than diffuse salivary inflammatory elevation. This approach may support non-invasive triage and monitoring along the oral- brain axis, pending independent, longitudinal validation.

BackgroundPreoperative biliary stenting alters biliary colonization and may reduce the effectiveness of perioperative antibiotic prophylaxis in pancreatoduodenectomy. Although broader-spectrum regimens have been associated with improved infectious outcomes, their microbiological adequacy in routine clinical practice remains poorly defined. We therefore evaluated the real-world adequacy of a prolonged ampicillin-sulbactam protocol, its association with infectious outcomes and survival, and the potential impact of a universal piperacillin-tazobactam strategy. MethodsWe analyzed all consecutive patients who underwent elective pancreatoduodenectomy from 2002 to 2023 at our tertiary center. Demographic, operative, microbiological, and outcome data were retrieved from a prospectively maintained database. Patients were stratified by stent status. Adequacy of prophylaxis was defined as the full in vitro susceptibility of all bile isolates. The outcomes included 30-day infectious morbidity, clinically relevant POPF, PPH, DGE, reoperation, 30- and 90-day mortality and long-term survival. A coverage simulation was performed to compare ampicillin-sulbactam with a hypothetical universal piperacillin-tazobactam. Statistical methods included chi-square/Fishers exact tests, Mann-Whitney U tests, Cox models, McNemars test and Poisson regression. ResultsOf 956 patients, 424 (44%) had a biliary stent. Technical complications were comparable between groups, and rates of POPF and PPH were not increased. However, infectious morbidity was higher in stented patients, including sepsis (RR 1.62, 95% CI 1.05-2.51) and postoperative cholangitis (RR 2.20, 95% CI 1.36-3.56). Thirty- and 90-day mortality were increased (RR 2.88 and 2.73) but lost significance after adjustment. Bile cultures predominantly yielded Enterococcus and Enterobacterales with low ampicillin-sulbactam susceptibility. Overall adequacy was 21.7%. Among patients with bile cultures (n = 474), ampicillin-sulbactam covered 43.7% (207/474) versus 81.2% (385/474) with piperacillin-tazobactam; in stented patients with cultures (n = 397), coverage increased from 41.8% to 78.1%. Adequate ampicillin-sulbactam coverage was not associated with reduced infectious outcomes in Poisson models. ConclusionPreoperative stenting creates a polymicrobial, partially resistant biliary niche that ampicillin-sulbactam does not sufficiently cover. Our data shows that a piperacillin-tazobactam strategy substantially improves coverage and was therefore implemented at our center. Core message- Stented patients exhibit a distinct infectious risk profile characterized by Enterococcus-and Enterobacterales-dominated bile colonization rather than increased rates of technical complications. - In stented patients, real-world microbiological coverage of ampicillin-sulbactam was limited, and in vitro susceptibility did not independently translate into reduced postoperative infectious morbidity. - Broader prophylaxis, such as piperacillin/tazobactam, aligns with the actual flora and nearly doubles theoretical coverage, addressing the mismatch between stent-associated biofilms and narrow regimens.

ObjectivesTo quantify how urine sample type and polymicrobial context impact antimicrobial resistance (AMR) in urinary tract infections (UTIs), using routine diagnostics at scale. MethodsIn this retrospective, single-centre study, we analysed 188,687 urine cultures from the Institute of Medical Microbiology, University of Zurich, Switzerland (January 2015 to May 2023). We compared midstream urine (MU), indwelling catheter (IDC), and intermittent catheter (IMC) samples. Samples were classified as negative, bacteriuria, or UTI, by meeting a microbiological UTI threshold ([&ge;]105 CFU/mL). We compared sample types using covariate-adjusted regression and constrained ordination for community composition. In bimicrobial cultures, we assessed co-occurrence using adjusted pairwise odds ratios and degree-preserving permutation null models, supported by partner-choice analyses. AMR was modelled as acquired resistance (AR) and total resistance (TR: acquired + intrinsic) probabilities, with predictor contributions quantified using mutual information. ResultsAmong 186,819 MU, IMC, IDC samples, 56,867 met the UTI threshold. Catheter-associated UTIs (IDC and IMC) were ~60% more likely to be polymicrobial than MU samples. Community composition differed by sample type (p<0{middle dot}001). In IDC, Escherichia coli was less prevalent than in MU, but device-associated pathogens like Pseudomonas aeruginosa and Candida albicans were enriched. Most species-pairs showed no increased co-occurrence after adjusting for covariates, but a subset showed reproducible enrichment across methods (e.g., C. albicans-C. glabrata). Organism identity was the dominant determinant of AMR, with the highest mutual information across AR and TR. AR was higher in IDC for common uropathogens (e.g., E. coli). Co-isolation with hospital-associated partners (e.g., Enterococcus faecium) was associated with further AR increase. From 2015 to 2023, AR increased from ~48% to ~60%, with rising {beta}-lactam (+{beta}-lactamase inhibitor) resistance and declining fluoroquinolone resistance in Enterobacterales. ConclusionsSample type and co-isolated partners provide clinically actionable information beyond pathogen identity and could support more context-aware reporting and empiric prescribing.

IntroductionDigital technologies are reshaping how health professionals are trained, and extended reality (XR) has gained attention as a tool for skills development in dental education. Yet, successful integration depends largely on educators perceptions, readiness, and working conditions. This study aimed to explore dental educators views of the educational value of XR, what barriers they experience, and how familiarity with immersive technologies relates to their use in teaching. Materials and MethodsA cross-sectional, web-based survey was conducted among dental educators. The questionnaire included items on demographics, familiarity and frequency of XR use, and perceptions of educational value, barriers, and curricular integration. Descriptive statistics were calculated, and Spearman correlation analyses were performed to explore associations between familiarity, use, and perceived benefits of XR. ResultsRespondents reported positive attitudes toward XR, particularly for improving students understanding of complex anatomy (mean = 6.02/7), skill development (5.68/7), and confidence and preparedness for clinical practice (5.08-5.20/7). XR was mainly viewed as a complement to traditional teaching rather than a replacement (mean = 3.77/7). Strong correlations were observed between perceived improvements in confidence, skills, and clinical readiness (r = 0.71 - 0.89, P < 0.0001). High costs, limited technical support, and time constraints were the most prominent barriers to usage. ConclusionOverall, dental educators appear open to XR but constrained by structural and organizational factors rather than a lack of interest. Faculty development, hands-on training opportunities, and institutional support may therefore be essential to translating positive perceptions into meaningful and sustained integration of immersive technologies in dental curricula.

BackgroundFailure of tooth eruption (FTE) encompasses mechanical impaction, primary failure of eruption (PFE), and syndromic disturbances. Since the seminal review by Suri et al. (2004), advances in genetics and surgical protocols warrant comprehensive synthesis. ObjectiveTo evaluate PTH1R mutation prevalence, diagnostic accuracy of clinical/radiographic criteria, comparative effectiveness of open versus closed surgical exposure for impacted canines, prognostic factors for supernumerary-associated eruptions, and management outcomes for PFE and syndromic disorders across six domains. MethodsPubMed/MEDLINE, Cochrane Library, and Google Scholar were searched (January 2004-February 2026). To enhance reproducibility, databases with broad public accessibility were prioritized. Google Scholar was used only for citation tracking and not as a primary database to minimize algorithmic bias and irreproducibility. PRISMA 2020 guidelines were followed. Protocol registered on OSF (DOI: 10.17605/OSF.IO/R5X76). Inclusion criteria: RCTs, cohort, case-control, and diagnostic accuracy studies. Genetic testing was considered the highest reference standard for diagnostic accuracy. Risk of bias assessed using ROBINS-I, QUADAS-2, and RoB 2.0. Meta-analyses used random-effects models with Hartung-Knapp adjustment. Heterogeneity was assessed using I{superscript 2} statistics, with sources explored through subgroup analyses, meta-regression, and prognostic factor analysis. GRADE evaluated evidence quality. Forest plots and funnel plots are provided in Figures 3-8 and Supplementary Figures S1-S15. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/26346646v1_fig3.gif" ALT="Figure 3"> View larger version (10K): org.highwire.dtl.DTLVardef@1d71b0forg.highwire.dtl.DTLVardef@1318309org.highwire.dtl.DTLVardef@1920208org.highwire.dtl.DTLVardef@c36c6f_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 3:C_FLOATNO Forest Plot - Treatment Duration Difference (Closed vs. Open Exposure). Forest plot comparing total treatment duration (months from exposure to final alignment) between closed and open surgical exposure techniques for impacted maxillary canines (Domain 3). Data from 8 studies comprising 1,287 canines. Closed exposure was associated with significantly shorter treatment duration (mean difference -4.7 months; 95% CI: -7.3 to -2.1; p < 0.001). Heterogeneity was moderate to high (I{superscript 2} = 64.1%), partially explained by study design in meta-regression (RCTs vs. cohorts, p = 0.04). The 95% prediction interval (-9.8 to 0.4 months) indicates the range within which the true effect in a future study would fall, supporting individualized technique selection. All eight studies favored closed exposure, though confidence intervals for three cohort studies crossed zero. Study weights ranged from 4.0% to 18.2%. RCTs (Parkin 2013, Bazargani 2019, Smailiene 2020, Chaushu 2021) showed slightly larger effect sizes (range: -3.8 to -6.1 months) compared to cohort studies (Becker 2010, Fleming 2015, Kokich 2012, Zuccati 2018; range: -3.2 to -6.4 months). Diamond represents pooled estimate; squares represent individual study weights with horizontal lines indicating 95% confidence intervals. C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/26346646v1_fig8.gif" ALT="Figure 8"> View larger version (40K): org.highwire.dtl.DTLVardef@42959org.highwire.dtl.DTLVardef@136c662org.highwire.dtl.DTLVardef@11a59e3org.highwire.dtl.DTLVardef@1035b2a_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 8:C_FLOATNO Forest Plot - Spontaneous Eruption After Supernumerary Removal. Forest plot of spontaneous eruption rates after supernumerary removal alone from 12 studies (1,456 patients) across Domain 4. Reported rates ranged from 48% to 68% across studies (I{superscript 2} = 71.2%). High heterogeneity reflects differences in patient age (deciduous vs. mixed vs. permanent dentition), supernumerary morphology (conical vs. tuberculate), timing of intervention, supernumerary position (palatal vs. labial vs. between roots), tooth type affected (central incisor most common), and follow-up duration (range 1-5 years). With adjunctive orthodontic measures (space creation, traction, or both), success rates increased to 81-90% across 8 studies (892 patients). Study weights ranged from 8.4% to 8.9%. Prognostic factor analysis (Table 6) identified favorable factors including removal during deciduous dentition (OR 2.5-5.5), conical supernumerary morphology (OR 3.0-6.5), and incomplete root formation of the permanent incisor (OR 2.5-5.0). Unfavorable factors included tuberculate morphology (OR 0.2-0.4) and complete root formation (OR 0.2-0.5). Diamond represents pooled estimate; squares represent individual study estimates with horizontal lines indicating 95% confidence intervals. C_FIG ResultsFrom 3,587 records, 94 studies (9,156 patients) were included across six domains. Overall certainty of evidence ranged from low to moderate due to observational designs and heterogeneity. Domain 1 (Genetic Basis): PTH1R mutation prevalence in PFE ranged from 52-90% (16 studies, 487 patients; I{superscript 2} = 68%; Figure 6). Heterogeneity reflected differences in familial vs. sporadic cases and referral bias. Population-level prevalence remains unknown. Sixty-three variants identified. Domain 2 (Diagnostic Accuracy): "Failure to respond to orthodontic force" showed sensitivity 94% (95% CI: 91-97%) and specificity 96% (93-98%). "Progressive posterior open bite" showed sensitivity 92% (88-95%) and specificity 89% (84-92%). Reference standard heterogeneity (I{superscript 2} = 45-65%) addressed through bivariate and HSROC models. CBCT provided superior root resorption detection (97% vs. 68%; p < 0.001). Domain 3 (Canine Impaction): Open (91% [88-94%]) and closed (93% [89-95%]) exposure achieved comparable success (I{superscript 2} = 52%). Closed exposure was associated with shorter treatment duration (mean difference -4.7 months [-7.3 to -2.1]; I{superscript 2} = 64%; Figure 3) and lower postoperative pain (-1.9 VAS [-2.6 to -1.2]; I{superscript 2} = 58%; Figure 4). Prediction intervals (-9.8 to 0.4 months) support individualized technique selection. Funnel plots showed no significant publication bias (Figure 7). Domain 4 (Supernumerary): Spontaneous eruption after removal alone: 48-68% (I{superscript 2} = 71%; Figure 8); with adjunctive orthodontics: 81-90%. Heterogeneity reflected patient age, supernumerary morphology, and timing of intervention. Favorable factors: deciduous removal (OR 2.5-5.5), conical morphology (OR 3.0-6.5), incomplete root formation (OR 2.5-5.0). Domain 5 (PFE Management): Orthodontic force application failed in 88-98% and caused adjacent tooth ankylosis in 25-50%. Prosthodontic rehabilitation achieved functional occlusion in 82-94%. Implant success: 85-95%. Meta-analysis not performed due to critical heterogeneity. Domain 6 (Syndromic): Cleidocranial dysplasia alignment: 61-75%. Osteopetrosis extraction-associated osteomyelitis: 33%, favoring conservative management. Narrative synthesis only. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/26346646v1_fig6.gif" ALT="Figure 6"> View larger version (40K): org.highwire.dtl.DTLVardef@15622eborg.highwire.dtl.DTLVardef@e7403org.highwire.dtl.DTLVardef@e27724org.highwire.dtl.DTLVardef@1fbe10a_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 6:C_FLOATNO Forest Plot - PTH1R Mutation Prevalence. Forest plot of PTH1R mutation prevalence in clinically diagnosed primary failure of eruption (PFE) from 16 studies (487 patients) across Domain 1. The reported prevalence varied substantially across studies, ranging from 52% to 90% (I{superscript 2} = 68%). Heterogeneity reflects differences in diagnostic criteria, patient selection (familial vs. sporadic cases), and referral bias. Subgroup analysis showed higher prevalence in familial cases (range 79-92%; 9 studies) compared to sporadic cases (range 54-71%; 12 studies). Meta-regression showed no significant association with geographic region, mutation detection method, or year of publication (p > 0.05 for all). Trim-and-fill analysis suggested one potentially missing study with negligible impact on pooled prevalence. Study weights ranged from 5.7% to 6.8%. The most frequently reported studies include Frazier-Bowers 2010 (0.75, 95% CI: 0.58-0.87), Risom 2013 (0.82, 95% CI: 0.66-0.92), and Park 2025 (0.89, 95% CI: 0.74-0.96). Reported estimates should not be extrapolated to unselected clinical populations; population-level prevalence remains unknown. Diamond represents pooled estimate; squares represent individual study estimates with horizontal lines indicating 95% confidence intervals. C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/26346646v1_fig4.gif" ALT="Figure 4"> View larger version (17K): org.highwire.dtl.DTLVardef@1737e7forg.highwire.dtl.DTLVardef@175c6a4org.highwire.dtl.DTLVardef@1446af8org.highwire.dtl.DTLVardef@caff01_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 4:C_FLOATNO Forest Plot - Postoperative Pain Difference (Closed vs. Open Exposure). Forest plot comparing postoperative pain scores (visual analog scale, VAS 0-10 at 24-48 hours) between closed and open surgical exposure techniques for impacted maxillary canines (Domain 3). Data from 5 studies comprising 842 patients. Closed exposure was associated with significantly lower pain scores (mean difference -1.9; 95% CI: -2.6 to -1.2; p < 0.001). Heterogeneity was moderate (I{superscript 2} = 58.2%), reflecting differences in pain measurement timing (24h vs. 48h), analgesic protocols, and study design (RCT vs. cohort). The consistent direction of effect across all studies supports robustness of findings. All five studies favored closed exposure for reduced postoperative pain. Study weights ranged from 17.5% to 22.4%. RCTs (Parkin 2013, Bazargani 2019, Chaushu 2021) showed slightly larger effect sizes (range: -1.8 to -2.4) compared to cohort studies (Becker 2010, Fleming 2015; range: -1.2 to -1.6). Diamond represents pooled estimate; squares represent individual study weights with horizontal lines indicating 95% confidence intervals. C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/26346646v1_fig7.gif" ALT="Figure 7"> View larger version (29K): org.highwire.dtl.DTLVardef@12bbffdorg.highwire.dtl.DTLVardef@1497eb8org.highwire.dtl.DTLVardef@1e879eorg.highwire.dtl.DTLVardef@59d3ae_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 7:C_FLOATNO Funnel Plot - Publication Bias for Canine Studies. Funnel plot assessing publication bias for 7 studies comparing treatment duration between open and closed surgical exposure for impacted maxillary canines (Domain 3). The plot appears reasonably symmetrical, with studies distributed evenly around the pooled estimate. Eggers test was non-significant (p = 0.38), suggesting no strong evidence of publication bias for this outcome. Each circle represents an individual study. The funnel shape represents the pseudo 95% confidence interval limits. The symmetrical distribution indicates that small and large studies are similarly distributed around the pooled effect estimate, supporting the robustness of the finding that closed exposure is associated with shorter treatment duration (mean difference -4.7 months; 95% CI: -7.3 to -2.1). The absence of publication bias strengthens confidence in the meta-analytic findings for this outcome. C_FIG ConclusionsThese findings support a paradigm shift toward genetically informed orthodontic decision-making across six integrated domains. PTH1R mutations are frequently reported in PFE, though population prevalence remains unknown. Open and closed canine exposure techniques have comparable success; closed exposure offers advantages in comfort and treatment duration. Early supernumerary intervention improves outcomes. Heterogeneity across domains reflects clinical diversity and was addressed through appropriate statistical methods. Orthodontic forces should be avoided in confirmed PFE. RegistrationOpen Science Framework (DOI: 10.17605/OSF.IO/R5X76)

Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, and South Africa. 476 (12%) "resisters" remained free of Mtb infection despite substantial exposure to highly infectious TB patients. GWAS identified a novel chromosome 13 locus (rs1295104126) associated with resistance across the multi-ancestry meta-analysis. Comparing Mtb-infection to all uninfected contacts, irrespective of exposure, yielded a different locus on chromosome 6 (rs28752534), near the HLA-II region. These findings demonstrate a common genetic basis for resistance to Mtb infection across multi-ancestral cohorts with potential to elucidate novel mechanisms of protection from Mtb infection.

BackgroundClostridium perfringens can cause life-threatening extraintestinal infections in immunocompromised patients, an area in which we have little information regarding strain factors that impact patient risks and outcomes. MethodsWe conducted genomic-epidemiologic analyses on C. perfringens isolates from 70 patients seen at Brigham and Womens Hospital over 2021-2024. Genomic analyses evaluated strain profiles within a broader context of 2,321 C. perfringens genomes from foodborne, veterinary, clinical, and environmental sources to identify factors associated with invasive infections. ResultsOf 70 patients with C. perfringens infections (mean age 67.6 years), 32 had invasive infections, of which two-thirds had active malignancies, and more than half were immunocompromised. Patients with invasive infections had a significantly higher 90-day mortality of 43.8% vs. 18.4% (p=0.035) and a higher median Charlson Comorbidity Index (6 vs. 3; p=0.003). Notably, no patient isolates were clonal, verifying the absence of hospital-based transmission. Patient isolates showed increased carriage of hyaluronidases (nagHIJKL), sialidases (nanIJ), and perfringolysin O (pfoA). Genomic-epidemiologic analyses identified a new independent association between the NagL hyaluronidase (OR 3.90, 95% CI 1.14 - 16.24) in highly morbid invasive infections. ConclusionWe present a comprehensive genomic analysis of C. perfringens and of strains infecting immunocompromised patients, including epidemiologic associations of the hyluronidase NagL, NanIJ sialidase, and perfringolysin O in highly morbid invasive infections. These genes provide potential markers to identify high morbidity strains that can infect these populations and to further elucidate their role in invasive infections.

IntroductionHemophagocytic lymphohistiocytosis (HLH) is a serious condition induced by Dengue virus which becomes fatal if not detected early and treated appropriately. So objectives of the present study are to observe the different patterns of presentations, clinical features and outcome of HLH induced by Dengue. MethodsIn this observational study, 14 patients admitted and diagnosed HLH as per diagnostic criteria, were included after informed written consent. Study conducted in a period of six months from 01/07/2025 to 31/12/2025. All patients were followed up till discharge. After collection, all data were analyzed by Microsoft Excel 2010. Ethical clearance was taken from Ethical Review Board of the Medical College. ResultsAmong 14 cases, male were more affected then the female (78.6% VS 21.4%) and majority were in between 20 to 50 years age groups. Clinical data showed, all 14 cases had fever for >7 days, joint pain 3(21.4%), headache 11(78.6%), skin rashes 10(71.4%), retro-orbital pain 2(14.3%), vomiting 11(78.6%),bleeding 10(71.4%), cough 4(28.6%), loose motion 9(64.3%), abdominal pain 7(50.0%), anorexia 2(14.3%), Melaena 2(14.3%), jaundice 4(28.6%) and spleenomegaly 9(64.3%). One(7.1%) case had history of Hypertension. Laboratory data showed different level of Bi or Pancytopenia, high ferritin, high TG, low fibrinogen, raised liver enzymes and low sodium. Dengue RT PCR and serology results showed 8(42.9%) cases were both IG M and Ig G dengue antibody positive, 6 cases were RT PCR positive, 2 cases were IgM and another 4 cases were IgG positive. Outcome of patients revealed, among all 14 cases12(85.8%) patients improved uneventfully and 2 were shifted to ICU where one improved and one died. ConclusionDengue is prevailing for long time and different complications are evolving and HLH is a relatively newer incident among the dengue patients. Infection by different serotypes at different time or multiple dengue serotype infection may be related with HLH and it might be a future subject to explore and to evaluate.

BackgroundThere is a need for synthetic peptide-based serologic assays that exploit avidity to replace whole antigens while enabling low-cost diagnostics in resource-limited settings. ObjectiveTo evaluate the diagnostic accuracy of a polymeric peptide-based ELISA leveraging avidity to enhance signal. MethodA 15-member SARS-CoV-2 peptide library corresponding to multiple epitope clusters and proteins was screened by indirect ELISA using pooled sera from RT-PCR-confirmed COVID-19 patients to identify peptides with possible diagnostic utility. The identified lead candidate, S559, possessed terminal cysteine-substitution to allow disulfide polymerization, and the resulting avidity gain was evaluated by comparing the apparent dissociation constant (KDapp) before and after depolymerization with N-acetylcysteine. The performance of an optimized ELISA using S559 was evaluated on 1,222 prospectively collected COVID-19 serum samples and 218 biobanked pre-COVID control serum samples. ResultsPolymeric S559 with a KDapp of 29.26 nM-1was demonstrated to have a 218% avidity gain relative to the completely depolymerized form. At pre-defined thresholds, the optimized S559 ELISA has a sensitivity and specificity of 83.39% (95%CI: 81.18% and 85.43%) and 96.79% (95%CI: 93.50% and 98.70%), respectively. At post hoc thresholds determined by Youden index, sensitivity and specificity reached 95.01 (95% CI: 93.63% - 96.16%) and 100.00% (95% CI: 98.32% - 100.00%), respectively. ConclusionHomomultivalent epitope presentation using polymeric S559 allows a highly specific immunoassay using human sera that may have important value in detecting antibodies, whether for diagnosing infection, confirming vaccination status or conducting surveillance.

IntroductionDengue has been prevalent in a regular fashion in Bangladesh and Chattogram for the last 6-7 years and is showing some serotype twisting. So, the objectives of the present study were to explore the burden of dengue serotypes in Chattogram. MethodsIn this study, 223 Dengue RT-PCR positive patients were evaluated for serotyping. Gender and age group, along with cycle threshold (CT) values, were also collected. Data after collection were compiled, analyzed, and plotted in Microsoft Excel and GraphPad Prism 10.4. Ethical clearance was taken to conduct the study. ResultsAmong 223 patients analyzed, males and females were found near equal (113 and 110). Middle-aged patients were more than the extremes of age. The mean {+/-} SD of age was 33.55 {+/-} 13.67 years. Regarding serotype distributions, isolated Den 1, Den 2 and Den 3 were found 1.3%, 73.1% and 6.7%, respectively. Concurrent infections with multiple serotypes were observed in several patients, most notably the Den 2 and Den 3 combination, which accounted for 14.3% (n=32) of the cases. Other co-infections were less frequent: the Den 1 and Den 2 pairing appeared in 3.6% (n=8) of the cohort, while triple-serotype infections (Den 1, 2, and 3) and Den 3/Den 4 pairings were rare, each occurring in only 0.4% of patients. Statistical analysis of CT values revealed no significant sex-based differences for Den 2 and Den 3. However, significant variations in CT values were observed when comparing Den 1 against both Den 2 and Den 3 (p < 0.05). In contrast, the difference between Den 2 and Den 3 Ct values remained statistically insignificant. ConclusionIn the year 2025, Dengue serotypes 2 and 3 were found to be the most prevalent, both in isolated or in combinations and Den 1 and Den 4 were found minimum. Exposure to multiple serotypes and twisting from one serotype to another might influence the dengue outcome in future, which needs further exploration.

BackgroundHospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP), particularly those caused by multi-drug resistant organisms (MDROs), often require newer antibiotic treatment. The efficacy and safety of newer antibiotics compared to generic antibiotics in randomized controlled trials (RCTs) have not been evaluated before. MethodsIn this systematic review, we searched RCTs in the United States National Library of Medicine (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Ovid MEDLINE, Clinical Trials.gov and Google Scholar databases published between 2013 and 2025. The primary efficacy endpoint was 28-day all-cause mortality. Secondary efficacy endpoints were clinical and microbiological response. Safety endpoint was nephrotoxicity. ResultsWe identified eight eligible RCTs involving 2,881 patients (1,450 patients treated with newer antibiotics and 1,431 patients treated with generic antibiotics) with HABP/VABP. The meta-analysis did not reveal any significant differences between newer and generic antibiotics for all-cause mortality at day 28 (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.72-1.30), clinical response (RR 1.04, 95%CI 0.93-1.17), and microbiological response (RR 1.05, 95%CI 0.89-1.24). However, newer antibiotics showed significant lower occurrences of nephrotoxicity compared to colistin component (RR 0.30, 95%CI 0.11-0.79). In subgroup analysis, newer antibiotic regimens demonstrated significant improvement in microbiological eradication of carbapenem-resistant Gram-negative bacilli (RR 1.50, 95%CI 1.18-1.90). ConclusionsNewer antibiotics showed similar efficacy and safety in treating HABP/VABP compared to generic drugs. The superiority in microbiological eradication of carbapenem-resistant Gram-negative bacilli of newer antibiotics could suggest that future trials should be targeted for those patients to improve understanding of their therapeutic use and pathophysiology of these conditions. Key pointsNewer antibiotics, despite broader antimicrobial coverage, have not significantly outperformed generic comparators in terms of 28-day all-cause mortality, clinical, or microbiological response in patients with Gram-negative HABP/VABP. This may reflect limitations in current trial designs focused primarily on regulatory approval.

BackgroundSevere Fever with Thrombocytopenia Syndrome (SFTS) is an acute infectious disease with high mortality. This study aimed to develop a quantitative scoring system for grading SFTS severity using dynamic clinical data. MethodsA retrospective study included 547 confirmed SFTS patients from two hospitals. Clinical data were collected over a 14-day course (divided into four phases). Patients were grouped into survivors (n=451) and non-survivors (n=96). Statistical analyses, including Kaplan-Meier curves and log-rank tests, were performed. An external validation cohort of 44 new patients was used to validate the scoring system via C-statistic, calibration curves, and decision curve analysis (DCA). ResultsOf 547 patients, 96 (17.55%) were non-survivors. Multivariate logistic regression identified six independent prognostic factors across phases: age, platelet (PLT), aspartate aminotransferase (AST), and creatinine (Cr) (days 5-7); age, red blood cell distribution width (RDW), Cr, and lactate dehydrogenase (LDH) (days 8-10); Cr and LDH (days 11-14). A scoring system (0-11 points) was developed, stratifying patients into low (0-3), intermediate (4-7), and high (8-11) risk groups, with adverse outcome rates of 1.04%, 22.92%, and 76.04%, respectively. Kaplan-Meier curves showed significant prognostic differences (log-rank P<0.001). External validation (44 cases) confirmed excellent performance: AUC 0.810-0.952, good calibration (Hosmer-Lemeshow P>0.05), and net clinical benefit (DCA Eavg 0.068-0.098, Emax 0.422-0.559). ConclusionA dynamic SFTS severity scoring system was developed and validated. Internal and external validation confirmed its reliability and clinical utility, providing a simple, practical tool for timely assessment and early intervention.