Infection
○ Springer Science and Business Media LLC
Preprints posted in the last 90 days, ranked by how well they match Infection's content profile, based on 15 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.
Banava, S.; Radaic, A.; Pachiyappan, K.; Cheng, N. F.; Hernandez-Kapila, Y. L.; Gansky, S. A.
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Background The COVID-19 pandemic has caused significant global mortality. Despite declining infection rates, new variants of SARS-CoV-2 continue to emerge, necessitating new prevention strategies. Objective This study aimed to evaluate the effect of four over-the-counter (OTC) antiseptic mouthwash/gargling solutions in the U.S., compared with a distilled water control, on SARS-CoV-2 viral load across multiple oral and oropharyngeal sample types. Methods This pilot single-center randomized controlled clinical trial enrolled adults in the San Francisco Bay Area, California, who tested positive for COVID-19. Participants were randomized to distilled water, chlorine dioxide, hydrogen peroxide, cetylpyridinium chloride, and essential oils. Participants were instructed to rinse and gargle four times daily for four weeks using standardized instructions to ensure protocol adherence. Samples were collected on Days 1, 7, and 28 and analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The primary outcome was the change in SARS-CoV-2 viral load from baseline to Day 28, assessed using cycle threshold (Ct) values. Secondary outcomes included self-reported clinical symptoms and hospitalization. Results Forty-nine participants completed the study. No mouthwash demonstrated a statistically significant reduction in SARS-CoV-2 viral load over time. Cetylpyridinium chloride showed a transient increase in Ct values on Day 7 that was not sustained on Day 28. At baseline, throat swab samples had the lowest Ct values across all sample types. Due to limited subgroup sample sizes for secondary outcome measures, no statistical or moderator analyses were conducted. Conclusion Further large-scale randomized trials are needed before recommending antiseptic mouthwashes for SARS-CoV-2 prevention or management.
Boontharak, A.; Amornsettachai, P.; Visuttiwattanakorn, S.
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The in vitro study aimed to evaluate linear dimensional shifts in intraoral photographs of the esthetic zone captured using two smartphone cameras--the iPhone 15 Pro Max and the Samsung Galaxy S23 Ultra--compared to a digital single-lens reflex (DSLR) camera, which is regarded as the gold standard for dental photography. Imaging was performed under controlled conditions using a custom-designed stand and stabilizer to maintain a consistent distance and angle between the dental model and the photographic devices. Standardized frontal and occlusal images of the anterior maxillary region were acquired, and point-to-point linear measurements between specified dental landmarks were performed using calibrated digital imaging software. Each measurement was conducted triple and then averaged across various samples per image to guarantee precision and dependability. Friedmans test with Bonferroni correction was applied for statistical analysis to evaluate differences among the imaging devices. The results indicated no statistically significant variations in linear measures between the DSLR and the Samsung Galaxy S23 Ultra (p > 0.05), however minor inconsistencies were noted between the DSLR and the iPhone 15 Pro Max. It is important to acknowledge that all images were obtained utilizing the stabilization system, which contrasts with the conventional handheld approach applied in clinical environments and could impact the external validity of the results. The Samsung Galaxy S23 Ultra, in telephoto mode, demonstrated measurement precision similar to that of a DSLR camera, potentially serving as a reliable choice for clinical intraoral photography. The iPhone 15 Pro Max demonstrated potential, although minor measurement discrepancies.
Mahfouz, M.; Alzaben, E.
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BackgroundTrauma from occlusion (TFO) is a frequently under-recognized clinical entity. While narrative reviews exist, no prior systematic review has quantitatively synthesized the prevalence of TFO signs in orthodontic patients, the distribution of the Akerly classification for deep traumatic overbite, the efficacy of orthodontic intrusion, or the outcomes of immediate orthodontic repositioning of traumatized incisors. Furthermore, the knowledge-practice gap among orthodontists regarding trauma management has not been meta-analyzed. MethodsSystematic review and meta-analysis of observational and interventional studies, including cross-sectional studies, randomized controlled trials, and before-after studies. We searched PubMed (n=57), PubMed Central (n=538), the Cochrane Library (n=11: 2 reviews, 9 trials), and Google Scholar (~3,930) up to December 2025. Studies reporting prevalence of TFO signs, Akerly classification distribution, overbite reduction following orthodontic intrusion, success of immediate orthodontic repositioning, or orthodontist knowledge/practice were included. Random-effects meta-analyses were performed using the meta package in R (DerSimonian-Laird estimation for {tau}2). The protocol was not registered due to the exploratory nature of this multi-domain synthesis; however, the methodology strictly adhered to PRISMA 2020 guidelines. ResultsTwenty-seven studies (n=8,432 participants) were included. The pooled prevalence of any TFO sign was 34% (95%CI:27-42%, I2=86%), with wide prediction intervals indicating substantial between-study variability. TFO was variably defined across studies as the presence of [≥]1 of the following: fremitus, increased mobility, occlusal interference, soft tissue trauma, or CR-CO discrepancy. Higher prevalence was observed in Class II malocclusion (46% vs. 22%). Among deep traumatic overbite cases classified using the Akerly system, Type II was most common (52%, 95%CI:44-60%), followed by Type I (31%) and Type III (17%). Orthodontic intrusion reduced overbite by a mean of 2.8 mm (95%CI:2.1-3.5, I2=72%); TAD-assisted intrusion produced greater reduction (3.4 mm) than conventional archwires (2.1 mm, p<0.001). Immediate orthodontic repositioning of traumatized incisors with light forces ([≤]50 g) achieved 91% success (95%CI:84-96%) at 12 months, comparable to splinting (84%), with no statistically significant difference between groups. The orthodontic group required fewer visits and reported better comfort. Meta-analysis of orthodontist knowledge showed correct awareness of specific trauma management protocols was below 40% in most domains, indicating a substantial evidence-practice gap. ConclusionThis first systematic review and meta-analysis on TFO in orthodontics provides preliminary quantitative benchmarks. One-third of orthodontic patients exhibit TFO signs; Akerly Type II is the dominant deep overbite pattern; orthodontic intrusion effectively reduces overbite by approximately 3 mm; immediate light-force repositioning is comparable to splinting in success and superior in efficiency. However, the disconnect between high clinical efficacy (e.g., 91% success of repositioning) and low practitioner awareness (<40%) represents a substantial translational gap in clinical practice. Assessment of publication bias was limited due to the small number of studies in several analyses (<10), precluding reliable funnel plot interpretation.
Mahfouz, M.; Alzaben, E.
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BackgroundWhite spot lesions (WSLs) affect up to 95% of patients after fixed orthodontic treatment. These demineralized areas harm aesthetics and may become more visible after tooth bleaching. Resin infiltration offers a micro-invasive masking technique. ObjectiveTo systematically review and meta-analyze the efficacy of resin infiltration for masking post-orthodontic white spot lesions compared with no treatment, placebo, or alternative remineralizing agents. MethodsWe followed PRISMA 2020 guidelines. We searched electronic databases (PubMed Central, Google Scholar, CORE, Epistemonikos, DOAJ) from inception to April 24, 2026, using database-specific search strings. We included randomized controlled trials (RCTs) and prospective clinical studies that evaluated resin infiltration for post-orthodontic WSLs in human participants. The primary outcome was change in lesion visibility. Two authors assessed risk of bias using Cochrane ROB-2 (RCTs) and ROBINS-I (non-randomized studies). We performed a random-effects meta-analysis using R (version 4.3.1; meta package) and estimated between-study variance ({tau}2) with the DerSimonian-Laird method. ResultsTen studies (6 RCTs, 4 prospective cohorts) with 1,204 patients and 3,847 WSLs met the inclusion criteria. Resin infiltration significantly reduced lesion visibility compared with no treatment (standardized mean difference [SMD] = -1.78; 95% CI: -2.24 to -1.32; p < 0.001; I2 = 65%) and compared with fluoride varnish (SMD = -1.42; 95% CI: -1.82 to -1.02; p < 0.001; I2 = 48%). The effect remained stable at 12-24 months. Patient satisfaction ranged from 84% to 94%. Mild transient sensitivity (11%) was the only reported adverse event. Funnel plot inspection showed no obvious small-study effects. ConclusionsResin infiltration shows high efficacy and durability for masking post-orthodontic white spot lesions, with a very large effect size. Clinicians should consider it the first-line minimally invasive aesthetic treatment before any tooth whitening procedure.
James-Pemberton, P.; Harper, D.; Wagerfield, P.; Watson, C.; Hervada, L.; Kohli, S.; Alder, S.; Shaw, A.
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A multiplex diagnostic test is evaluated for self-reported long COVID associated persistent symptoms and a poor recovery from a SARS-CoV-2 infection. A mass-standardised concentration of total antibodies (AC), high-quality (HQ) antibodies and percentage of HQ antibodies (HQ%) is assessed against a spectrum of spike proteins to the SARS-CoV-2 variants: Wuhan, , {delta}, and the Omicron variants BA.1, BA.2, BA.2.12.1, BA.2.75, BA.5, CH.1.1, BQ.1.1 and XBB.1.5 in three cohorts. A cohort of control patients (n = 46) recovered (CC) and a cohort of self-declared long COVID patients (n = 113) (LCC). A nested Receiver Operating Characteristic (ROC) analysis, performed for the variant with lowest HQ concentration in the spectrum, produced an area under the curve and AUC = 0.61 (0.53-0.70) for the CC vs LCC cohorts. For the LCC cohort, the cut-off thresholds for AC = 0.8 mg/L, HQ = 1.5 mg/L and HQ% of 34% were determined, leading to a 71% sensitivity and 66% specificity derived by the Youden metric. The cohorts may be fully classified based on ROC and outlier analysis to give an incidence of persistent virus 62% (95% CI 52% - 71%), hyperimmune 12% (95% CI 7% - 20%) and unclassified, 26% (95% CI 18% - 35%). The overall diagnostic accuracy for both the hyper and hypo immune is 69%. All clinical interventions can now be tailored for the heterogenous long COVID patient cohort.
Neveux, M. R.; Hylin, R.; Ruiz Gonzalez, V.; Lopez Parra, A. P.; Onoja, A.; Sirivichayakul, S.; Sulaimon, A. A.; Rwibasira, G.; Ochwoto, M.
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IntroductionDiagnostics have become the fundamental backbone of HIV prevention, treatment and long-term retention in care, and are critical to achieving the 95-95-95 UNAIDS targets. To effectively reach underserved and remote populations, diagnostic technologies must be cost-effective, robust, user-friendly and suitable for settings with limited infrastructure. Among available testing modalities, rapid diagnostic tests (RDTs) play a central role in expanding HIV testing coverage. Earlier generations of RDTs were limited by their inability to detect acute HIV, with limited ability to detect p24 antigen (Ag), an early marker of HIV infection, which is expected to shorten the diagnostic window to two-to-three weeks. The introduction of fourth-generation RDTs, which detects both chronic and acute HIV infection through p24 Ag detection, was designed to ensure that the traditional diagnostic window of two-to-three months is shortened to approximately two-to-three weeks. However, integrating these assays into existing testing algorithms requires clear evidence that they meet high standards of quality and performance. This systematic review aims to assess the performance of WHO-prequalified fourth-generation Ag/Ab RDTs. MethodsWe performed a systematic search across six databases to identify studies evaluating Ag/Ab RDTs against laboratory reference standards in individuals aged 12 years and older, spanning 1 January 2010 to 31 December 2025. Outcomes were limited to measures of diagnostic accuracy. A meta-analysis focusing exclusively on WHO-prequalified fourth-generation RDTs was performed using a bivariate random-effect model. Results1,932 records were screened, of which 31 diagnostic accuracy studies from 19 countries were included. 15 studies used US-only approved products, 12 used WHO-prequalified products and four used commercially discontinued products. The pooled sensitivity of WHO-prequalified Ag/Ab RDTs for acute HIV infection (AHI) was 94% (95% CI: 86%-99%). An RNA threshold of [≥] 1,000,000 copies/mL was used as a proxy for high viraemia and used as a cut-off for the following analyses. The cut-off based analysis is considered more suited to decision-making, as it focuses on cases most likely to be associated with higher viraemia and greater potential for detection during the p24 Ag window. When using enzyme immunoassay (EIA) as the reference standard, the pooled p24 Ag sensitivity was 76% (95% CI: 62%-88%), and the pooled p24 Ag sensitivity when using nucleic acid amplification test (NAAT) as the reference standard was 75% (95% CI: 41%-97%). In the general population, the pooled sensitivity for p24 antigen detection was 77% (95% CI: 60%-92%). Amongst risk populations, only three studies had available raw data, and the pooled sensitivity was 62% (95% CI: 10%-97%). In plasma and serum specimens, pooled p24 Ag sensitivity was 74% (95% CI: 57%-88). DiscussionCollectively, these findings indicate that WHO-prequalified fourth-generation Ag/Ab RDTs can function as a scalable frontline screening tool, particularly in low- and middle-income countries, while offering incremental holistic detection through p24 Ag. Their effective deployment, however, depends on maintaining standard algorithm safeguards, including repeat testing and targeted laboratory referral when acute infection is suspected. ConclusionsResults from this meta-analysis support the use of WHO-prequalified fourth-generation Ag/Ab RDTs for general population screening. From a programmatic perspective, the added value of WHO-prequalified fourth-generation RDTs lies in their ability to combine rapid, decentralized access to testing, with incremental yet impactful improvements in holistic detection.
Fujita, H.; Takahashi, O.; Yada, N.; Tanaka, J.; Haraguchi, K.; Morioka, M.; Yaginuma, T.; Sasaguri, M.; Kokabu, S.; Habu, M.
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Objective: To identify Dickkopf-1 (DKK1) as a prognostically relevant candidate in head and neck squamous cell carcinoma and to evaluate whether DKK1 and cytoskeleton-associated protein 4 (CKAP4) expression is associated with cervical lymph node metastasis in tongue squamous cell carcinoma (TSCC). Methods: DKK1 was screened using the Human Protein Atlas Pathology Atlas. Immunohistochemical expression of DKK1 and CKAP4 was examined in 54 patients with primary TSCC (cT1-4N0) treated surgically between 2015 and 2020. Nine cases were excluded because of insufficient tissue blocks or inadequate staining quality, leaving 45 evaluable cases. Associations with delayed cervical lymph node metastasis were assessed together with conventional clinicopathological factors, including infiltrative growth pattern (INF) and pathological depth of invasion (pDOI). Results: In public database analysis, high DKK1 expression was associated with poorer overall survival in head and neck squamous cell carcinoma. In the TSCC cohort, pDOI [≥]5 mm and INF pattern c were significantly associated with cervical lymph node metastasis. Positive DKK1 and CKAP4 expression were also significantly associated with cervical lymph node metastasis. Furthermore, combined DKK1/CKAP4 positivity, when incorporated with INF and pDOI, provided additional risk stratification, and cases with all 3 factors showed a markedly increased likelihood of cervical lymph node metastasis. Conclusions: Expression of DKK1 and CKAP4 was associated with cervical lymph node metastasis in TSCC. Combined assessment of DKK1/CKAP4 expression with INF and pDOI may improve pathological risk stratification and may help identify patients who require closer neck evaluation and postoperative management.
Yi, B.; Kim, H. Y.; Sotka, W.; Estey, R.; Green, S. J.; Shiau, H.
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BackgroundGingival inflammation is associated with dysbiotic oral biofilms characterized by reduced nitrate-reducing capacity and diminished nitric oxide (NO) bioavailability. While dietary nitrate has been shown to influence oral microbial activity, the effects of sustained, localized nitrate delivery on oral biofilm ecology and gingival inflammation remain incompletely defined. Methods and findingsIn this randomized, double-blind, placebo-controlled trial, 30 adults with gingival bleeding were assigned to receive localized prebiotic nitrate ([~]0.989 mmol per dose) or placebo for 21 days. The primary outcome was mean bleeding on probing (mBOP). Secondary outcomes included modified Gingival Index (mGI), Quigley-Hein plaque index (QHPI), salivary nitrite (as a proxy for NO bioavailability), oral pH, and microbiome composition assessed by 16S rRNA gene sequencing. Nitrate supplementation significantly reduced mBOP (25.7% to 15.3%; p = 0.0002) compared to placebo. Salivary nitrite levels and oral pH increased, indicating enhanced nitrate metabolism. Microbiome analysis demonstrated enrichment of nitrate-reducing taxa, including Rothia mucilaginosa and Neisseria spp., and a relative reduction in inflammation-associated genera such as Prevotella and Porphyromonas. No significant differences were observed in plaque index, consistent with functional modulation of the biofilm rather than reduction in plaque accumulation. ConclusionsLocalized prebiotic nitrate supplementation was associated with reduced gingival inflammation and shifts in oral microbiome composition consistent with enhanced nitrate-reducing capacity critical in nitric oxide formation. These findings support a role for biofilm-directed nutritional modulation as a non-antimicrobial approach for managing gingival inflammation and improving nitric oxide bioavailability.
Mahfouz, M.; Alzaben, E.
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Background: Incisor extraction represents a strategic yet underutilized orthodontic treatment modality for managing anterior discrepancies. Despite its clinical relevance, the evidence base has not been systematically synthesized with meta-analytic techniques. Objective: To systematically review and meta-analyze the evidence on incisor extraction in orthodontic treatment, evaluating clinical outcomes and biomechanical efficacy in both maxillary and mandibular arches. Methods: A comprehensive search of open-access electronic databases (PubMed, LILACS, SciELO, Google Scholar, DOAJ, OpenGrey) and orthodontic journal archives was conducted from inception to January 11, 2026 following PRISMA guidelines. Eligible studies included randomized controlled trials, prospective cohort studies, and retrospective cohort studies with greater than or equal to 10 patients reporting quantitative outcomes following incisor extraction or incisor movement with premolar extraction. Primary outcomes included space closure efficiency, incisor position changes, root resorption, and stability. Risk of bias was assessed using ROBINS-I for observational studies and Cochrane RoB 2.0 for RCTs. Certainty of evidence was evaluated using GRADE. Results: From 1,842 identified records, 20 primary studies met inclusion criteria (4 RCTs, 16 observational studies), comprising 1,347 patients. Sixteen studies provided data for meta-analysis. With moderate-certainty evidence, mandibular incisor extraction (8 studies, n=412) demonstrated mean space closure of 5.2 mm (95% CI 4.8 to 5.6 mm, I-squared=34%) with favorable long-term stability (mean irregularity increase 0.3 mm, 95% CI 0.1 to 0.5 mm, I-squared=28%). Low-certainty evidence indicates clear aligner accuracy is limited to 78.9% of predicted incisor tip movement (3 studies, n=187, 95% CI 72.3 to 85.5%, I-squared=41%); these findings may not reflect newer generation aligner systems. Low-certainty evidence suggests maxillary incisor movement following premolar extraction (6 studies using tomographic imaging, n=387) results in palatal bone resorption (mean -0.43 mm, 95% CI -0.62 to -0.24 mm, I-squared=52%), with greater effects in adults versus adolescents (mean difference 0.31 mm, p = 0.02); although statistically significant, the magnitude may be clinically negligible in patients with adequate baseline alveolar thickness. Moderate-certainty evidence indicates en-masse retraction results in faster space closure than two-step retraction (4 RCTs, n=214, mean -4.2 months, 95% CI -5.8 to -2.6 months). Moderate-certainty evidence shows root resorption incidence is 12.4% (95% CI 8.7 to 16.1%), with subgroup analysis: greater than 2 mm threshold 13.2% (7 studies), at least one-quarter root length threshold 11.4% (5 studies). Low-certainty evidence suggests extraction versus non-extraction comparisons (4 studies, n=326) show no significant differences in relapse. Conclusions: Mandibular incisor extraction demonstrates favorable long-term stability with minimal profile changes but requires recognition of clear aligner accuracy limitations. Maxillary incisor movement carries risks including palatal bone resorption, particularly in adults, though the clinical significance may vary with baseline alveolar thickness. En-masse retraction results in faster space closure with comparable root resorption risk. Treatment decisions should consider patient-specific factors including age, alveolar bone morphology, malocclusion pattern, and appliance selection.
Heaton, L. J.; Santoro, M.; Cheung, H. J.; Preston, R. A.; Tranby, E. P.
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IntroductionDiscrimination within oral health care settings is increasingly recognized as a contributor to oral health inequities, shaping patient trust, care-seeking behaviors, and health outcomes. While prior research has documented discriminatory experiences among racially and ethnically minoritized populations, nationally representative evidence on discrimination and dignity in dental care among LGBTQ+ adults remains limited. This study examines differences in discrimination and microaggressions in dental settings by LGBTQ+ status, sexual orientation, and gender identity. MethodsThis study analyzed pooled data from the 2022-2025 waves of the State of Oral Health Equity in America (SOHEA) survey, a nationally representative survey of U.S. adults aged 18 and older. Discrimination was measured using the Everyday Discrimination Scale-Oral Care (EDSOC), and microaggressions were assessed using the Dignity in Oral Care Scale (DOCS). Descriptive and bivariate analyses compared mean scores across identity groups. Multivariable linear regression models estimated associations between LGBTQ+ status, sexual orientation, and gender identity with EDSOC and DOCS scores, adjusting for sociodemographic characteristics and dental insurance status. Analyses focused on group differences and associations and were conducted without applying survey weights. ResultsThe analytic sample included 15,591 adults from the 2022-2025 SOHEA surveys with complete data (52.5% of the total N=29,679); 12% identified as LGBTQ+. Overall, LGBTQ+ individuals in the analytic sample reported significantly higher mean discrimination (EDSOC: 2.97, SD=4.99) and microaggression (DOCS: 2.19, SD=3.22) scores than non-LGBTQ+ individuals (EDSOC: 1.72, SD=3.79; DOCS: 1.62, SD=2.80; p<0.001). Questioning individuals and those with gender identities categorized as "other" had the highest mean EDSOC and DOCS scores (p<0.001). In adjusted models controlling for sociodemographic and insurance factors, LGBTQ+ identity remained significantly associated with higher EDSOC ({beta}=0.16, 95% CI=0.11-0.21) and DOCS ({beta}=0.08, 95% CI=0.03-0.13) scores. Sexual orientation and gender identity differences persisted, with questioning and gender-diverse individuals experiencing significantly higher levels of discrimination and microaggressions in dental settings. DiscussionFindings demonstrate that LGBTQ+ adults, particularly adults identifying as questioning and those with nonbinary or other gender identities, experience disproportionate discrimination and microaggressions in dental care settings. Addressing interpersonal and structural sources of bias in oral health care is critical to advancing equity and improving access to respectful, high-quality care for LGBTQ+ populations.
Chaves, E. T.; Teunis, J. T.; Digmayer Romero, V. H.; van Nistelrooij, N.; Vinayahalingam, S.; Sezen-Hulsmans, D.; Mendes, F. M.; Huysmans, M.-C.; Cenci, M. S.; Lima, G. d. S.
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BackgroundRadiographic detection of caries lesions adjacent to restorations is challenging due to limitations of two-dimensional imaging and difficulties distinguishing true lesions from restorative or anatomical radiolucencies. Artificial intelligence (AI)-based clinical decision support systems (CDSSs) have been introduced to assist radiographic interpretation; however, different AI tools may yield variable diagnostic outputs, and their comparative performance remains unclear. ObjectiveTo compare the diagnostic performance of commercial and experimental AI algorithms for detecting secondary caries lesions on bitewings. MethodsThis cross-sectional diagnostic accuracy study included 200 anonymized bitewings comprising 885 restored tooth surfaces. A consensus group reference standard identified all surfaces with a caries lesion and classified each lesion by type (primary/secondary) and depth (enamel-only/dentin-involved). Five commercial (Second Opinion(R), CranioCatch, Diagnocat, DIO Inteligencia, and Align X-ray Insights) and three experimental (Mask R-CNN-based and Mask DINO-based) systems were tested. Diagnostic performance was expressed through sensitivity, specificity, and overall accuracy (95% CI). Comparisons used generalized estimating equations, adjusted for clustered data. ResultsSpecificity was high across all systems (0.957-0.986), confirming accurate recognition of non-carious surfaces, whereas sensitivity was moderate (0.327-0.487), reflecting frequent missed detections of enamel and dentin lesions. Accuracy ranged from 0.882 to 0.917, with no significant differences among models (p [≥] 0.05). Confounding factors, such as radiographic overlapping, marginal restoration defects, and cervical artifacts, were the main sources of misclassification. ConclusionsAI algorithms, regardless of architecture or commercial status, showed similar diagnostic capabilities and a conservative detection profile, favoring specificity over sensitivity. Improvements in dataset diversity, labeling precision, and explainability may further enhance reliability for secondary caries detection. Clinical SignificanceAI-based CDSSs assist clinicians by providing consistent detection. Their high specificity is particularly valuable in minimizing unnecessary invasive treatments (overtreatment), though they should be used as adjuncts rather than a replacement for expert judgment.
Saura-Lazaro, A.; Adolfo Bila, D.; Van den Bogaart, E.; Myburgh, H.; Fisher-Cunhete, M.; Vaz, P.; Paulussen, R.; Viljoen, L.; Rinke de Wit, T. F.; Naniche, D.
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Introduction: Viral load (VL) monitoring is the gold standard for antiretroviral therapy (ART) monitoring. Still, due to limited funds and infrastructure, many people living with HIV (PLHIV) in low- and middle-income countries do not receive timely VL testing. We evaluated the clinical performance and end-user acceptability of a prototype interferon gamma-induced protein 10 (IP-10) point-of-care (POC) test as a rule-out triage tool to identify individuals unlikely to have unsuppressed VL in PLHIV in Mozambique. Methods: A mixed-methods study was conducted between November 2023 and November 2024 at two primary healthcare facilities in Maputo Province. We enrolled 1,057 PLHIV on ART from stable and specialized risk clinics. Clinical performance of the IP-10 POC test (index test) was compared against plasma HIV VL (reference test; unsuppressed defined as >1000 copies/mL). Socio-demographic and clinical predictors of false-positive results were identified using multivariable logistic regression. Immediate acceptability was assessed through exit interviews on a subset of 43 PLHIV. Results: Among participants (71.7% female; median age 41.4 years), 12.0% had unsuppressed VL. The IP-10 POC test demonstrated high sensitivity (90.6%) and moderate specificity (35.6%). Specificity was higher in clinics treating stable patients (44.5% 95%CI: 39.7-49.3) compared to specialized risk clinics (26.5% 95%CI: 21.1-28.9). The proportion of false-positive results was also higher in patients attending specialized risk clinics. Independent predictors of false positivity included enrolment in a one-stop TB/HIV clinic (aOR=2.99 95%CI: 1.09-8.15), cotrimoxazole use (aOR=2.16, 95% CI: 1.13-4.13), and obesity (aOR=3.47 95%CI: 1.74-6.93). Acceptability was high: 70% of participants appreciated the test simplicity and rapid results, and 95.3% expressed interest in future testing. Most patients preferred finger-prick collection over venous draws. Conclusions: The IP-10 POC test is a highly sensitive triage tool, demonstrating superior performance among stable PLHIV enrolled in differentiated service delivery models like six-month multi-month dispensing. While factors associated with co-infections can reduce specificity, the test's high acceptability and potential to reduce confirmatory VL test demand suggests it could serve as a viable triage strategy for optimizing resources particularly in stable care pathways with a lower prevalence of inflammatory comorbidities. This could enable health systems to reallocate intensive monitoring toward higher-risk populations.
McCormick, K. M.; Amarasena, N.; Guzzo, G.
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Background: Periodontitis is defined by cumulative, irreversible tissue destruction, yet population-based measurement typically relies on cross-sectional indicators derived from retained teeth. Destruction that occurred earlier in life, particularly disease severe enough to result in tooth loss, is structurally excluded from these measures, potentially leading to systematic underestimation of lifetime periodontal burden. Objective: To develop and evaluate a measurement framework that estimates lifetime periodontal burden from cross-sectional data by explicitly incorporating informative tooth loss under etiological uncertainty. Methods: Data were drawn from 10,324 adults aged [≥]30 years participating in the 20090-2016 National Health and Nutrition Examination Survey (NHANES) who completed full-mouth periodontal examination and glycated hemoglobin (HbA1c) testing. Lifetime periodontal burden was estimated by combining observed clinical attachment loss in retained teeth with probabilistic contributions from missing teeth, using three alternative age-stratified attribution schedules derived from epidemiological studies of periodontal extraction. Performance was compared with conventional measures of periodontal severity and extent using distributional analyses, correlations with HbA1c, discrimination of diabetes status, and relative importance analysis. Age-adjusted models were treated as sensitivity analyses. Results: Estimated lifetime periodontal burden exhibited strong, monotonic age gradients across glycemic categories, in contrast to more attenuated patterns observed for severity and extent. Across attribution schedules, lifetime burden showed stronger correlations with HbA1c ({rho} = 0.30-0.32) than conventional measures. In multivariable models including all indices, lifetime burden retained an independent association with HbA1c, whereas severity and extent contributed little unique information. Discriminative performance for diabetes status was consistently higher for lifetime burden than for conventional measures and remained stable across attribution schedules. Conclusions: Lifetime periodontal burden can be estimated from cross-sectional data by explicitly modelling informative tooth loss rather than restricting measurement to retained teeth. Incorporating historical tissue loss under uncertainty yields a more coherent representation of cumulative periodontal destruction than snapshot-based measures and provides a methodological basis for life-course-oriented periodontal epidemiology.
Rodrigues, C. C.; Rebello, S. D.
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BackgroundCommercial dental artificial intelligence in 2026 is over-whelmingly diagnostic: caries, calculus, periapical, and bone-level detection on radiographs. The clinically harder question that follows every diagno-sis -- given a patients chart and most recent procedure, what should the dentist do next -- remains unsolved at general-dentistry scale. The closest published system, MultiTP (Chen et al., 2024), is a CNN-RNN restricted to partial-edentulism cases and provides neither calibrated uncertainty, structured rationale, nor an evaluation that treats the model as decision support rather than as an autonomous classifier. MethodsWe introduce DentaCoPilot, a recommender that, given a structured chart, returns (i) a calibrated top-K probability distribution over Current Dental Terminology (CDT) codes for the next procedure, (ii) a verbalised confidence label, (iii) an explicit abstain flag when context is insufficient, and (iv) a chartgrounded rationale. We compare four classical baselines (frequency bigram, TF-IDF + logistic regression, XGBoost, MultiTP-style CNN-RNN) and six large-language-model (LLM) variants (Claude Haiku, Sonnet + chain-of-thought, Sonnet + retrieval, Opus + chain-of-thought, Sonnet + classical prior, Opus + classical prior) on a synthetic chart corpus of 500 patients (1,284 test examples). All LLM inference is routed through the local Anthropic Claude Code CLI; every call is logged for full audit. ResultsOn apples-to-apples evaluation, classical baselines reach 0.567 top-1 / 0.967 top-5; pure LLM variants trail at 0.267-0.467 top-1. Prompt-conditioning a Sonnet LLM on the classical baselines top-10 candidates (M5) closes the gap: top-5 rises from 0.733 (pure Sonnet + chain-of-thought) to 0.933, matching classical baselines, while preserving rationale and abstention. Increasing the LLM backbone from Sonnet to Opus does not improve accuracy with or without priming. Calibration via temperature scaling and coverage-risk analysis is reported for the baselines. ConclusionPrompt-conditioning a small LLM on a classical baselines top-K is the most cost-effective LLM design we tested for next-procedure recommendation, and the design preserves the augmentation features that distinguish the system from an autonomous classifier. A pre-registered clinician-in-the-loop evaluation at the KLE Vish-wanath Katti Institute of Dental Sciences (Belgaum, India) and a real-data evaluation on the multi-institutional BigMouth dental data repository are the next stage of work.
Mahfouz, M.; Alzaben, E.
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Background: Management of transverse maxillary deficiency in children with severely destructed first permanent molars (FPMs) is challenging because traditional tooth-borne rapid palatal expanders rely on these teeth for anchorage. These teeth are often compromised by extensive caries or Molar Incisor Hypomineralization (MIH), rendering them unsuitable as anchor units. Miniscrew-assisted expansion techniques may offer solutions that bypass compromised teeth. Methods: A systematic literature search was conducted using PubMed, PubMed Central, Google Scholar, DOAJ, OATD, OpenGrey, BASE, and the Cochrane Library (CENTRAL) (January 2005 to January 2026). Citation tracking and reference screening supplemented the search. The review protocol was developed a priori following PRISMA recommendations but was not registered in PROSPERO. Inclusion criteria: randomized controlled trials, prospective/retrospective comparative studies ([≥]10 patients/group) involving children aged 6-18 years with transverse maxillary deficiency. During full-text screening, studies were selected if their patient populations could be reasonably inferred to contain children with compromised FPMs based on clinical context (e.g., studies in pediatric dentistry, patients referred for MIH or severe caries). Risk of bias was assessed using the Cochrane RoB 2.0 tool for RCTs and ROBINS-I for non-randomized studies. Random-effects meta-analyses using the DerSimonian-Laird method were performed for skeletal expansion (standardized mean difference, SMD), dental tipping (SMD), success rate (pooled proportion), and relapse (mean difference). Results: From 28,879 initially retrieved records, 23 studies (1,847 patients; mean age 11.4 +/- 2.3 years) were included after screening; 16 contributed to meta-analyses. Of these, 987 patients received miniscrew-assisted expansion and 860 underwent conventional expansion. Four appliance types were identified: hybrid hyrax, C-expander, MARPE/MSE, and miniscrew-anchored distalizers. Miniscrew-assisted expansion achieved significantly greater skeletal expansion than conventional expanders (SMD=1.24; 95% CI: 0.89 to 1.59; p<0.001; I2=58%). Miniscrew-assisted expansion significantly reduced dental tipping compared with conventional expansion (SMD= -0.98; 95% CI: -1.42 to -0.54; p<0.01; I2=51%). MARPE appliances demonstrated a pooled success rate of 93.9% (95% CI: 89.7% to 97.2%; I2=41%). Long-term data ([≥]5 years, 3 studies) suggested a possible reduction in relapse of approximately 65% with MARPE. Subgroup analysis showed no significant outcome differences between appliance types (p=0.24). GRADE evidence quality was moderate for skeletal/dental outcomes, high for success rate, and low for long-term relapse. Conclusion: Miniscrew-assisted expansion represents a predictable and minimally invasive strategy for children with compromised first permanent molars, achieving superior skeletal expansion with reduced dental side effects compared to conventional techniques. These findings support a stratified appliance selection approach based on individual patient characteristics.
Yu, X.; Yan, R.; Li, H.; Xie, Y.; Bi, M.; Li, Y.; Roccuzzo, A.; Tonetti, M. S.
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AimTo comprehensively characterize the salivary proteome in periodontitis using Orbitrap Astral data-independent acquisition mass spectrometry (DIA-MS), identify an atlas of differentially expressed proteins (DEPs), and develop a machine learning-derived multi-protein biomarker panel for non-invasive diagnosis of stage III/IV periodontitis. Materials and MethodsUnstimulated saliva samples from 199 participants (periodontal health/gingivitis, n=120; stage III/IV periodontitis, n=79) were analyzed by Orbitrap Astral DIA-MS. DEPs were identified, and pathway enrichment analysis was performed. A two-tier machine learning pipeline--integrating pathway-based feature selection with cross-validated evaluation--was applied to identify the optimal diagnostic panel. ResultsOrbitrap Astral DIA-MS quantified 5,597 salivary proteins and 1,966 DEPs (|log2FC|>0.5, FDR<0.05). Pathway analysis identified 14 periodontitis-relevant KEGG pathways, including Th17 cell differentiation, IL-17 signaling, neutrophil extracellular trap formation, and complement and coagulation cascades. A four-protein panel (TEC, RAC1, MAPK14, KRT17) achieved an area under the curve (AUC) of 0.985 {+/-} 0.010, with 83% sensitivity and 100% specificity. The panel was corroborated using public datasets. ConclusionsTo our knowledge, this study represents the first application of Orbitrap Astral DIA mass spectrometry in periodontitis research, establishing a disease-specific DEPs atlas and a salivary biomarker panel with high diagnostic accuracy for stage III/IV periodontitis, providing a foundation for future external validation studies.
Mahfouz, M.; Alzaben, E.
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Background: Impacted maxillary incisors present significant clinical challenges requiring interdisciplinary management. To date, no meta-analysis has quantitatively synthesized success rates specifically for impacted maxillary incisors. This systematic review and meta-analysis aimed to determine the pooled success rate of orthodontic traction for impacted maxillary incisors and identify factors influencing outcomes. Methods: A systematic review and meta-analysis of observational studies was conducted following PRISMA 2020 guidelines. A systematic search was performed in PubMed, Epistemonikos, Cochrane Library, and Google Scholar (January 2011 - March 5, 2026). Primary studies reporting success rates of orthodontic traction for impacted maxillary incisors were included. The primary outcome was successful eruption and alignment into the dental arch. Although the protocol was not registered in PROSPERO, the methodology was predefined, documented, and strictly followed to minimize risk of bias. Pooled success rates were calculated using a random-effects model (DerSimonian-Laird method) with R software (meta package). Heterogeneity was assessed using I2 statistics. Publication bias was evaluated using funnel plots and Egger's test. Quality assessment employed ROBINS-I. Results: Eleven studies with 2,847 patients were included in the systematic review; 2,149 patients from 11 studies provided sufficient data for quantitative synthesis. The pooled success rate was 82.3% (95% CI: 78.6-86.0%), with a prediction interval ranging from 70% to 91%. Considerable heterogeneity was observed (I2 = 78%, p < 0.001). Subgroup analysis showed that younger age (<14 years) was associated with significantly higher success rates (88.4% vs. 78.2%, p = 0.01). Mild impaction depth (<5mm) was associated with higher success rates (89.2% vs. 76.5%, p = 0.02). No significant publication bias was detected (Egger's test, p = 0.18); however, the power to detect publication bias is limited with fewer than 15 studies. Certainty of evidence was moderate due to heterogeneity and observational study designs. Conclusions: Orthodontic traction is an effective, though not universally successful, treatment modality, with a pooled success rate of 82.3% for impacted maxillary incisors, and success significantly associated with patient age and impaction severity. Early intervention and favorable impaction characteristics are associated with better outcomes
Campos, L. C.; Favreau, E.; Greene, D.; Blach, J.; Thomas, M.; Alsehaim, K.; Mutlu, L.; Elhadari, S.; Herwadkar, A.; Payne, J.; Lever, C.; Mahmoud, D.; Moreira, F.; O'Sullivan, M.; Berry, M.; Twigg, G.; Hart, A. C. J.; Joshi, N.; Fuller, S.; INTREPID Consortium, ; Smith, K. G. C.; Turro, E.; Cook, M. C.; Wallace, C.; Burns, S. O.
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BackgroundPatients with Common Variable Immunodeficiency (CVID) exhibit diverse clinical manifestations, indicating heterogeneity in pathogenic mechanisms. Systematic application of standardised phenotyping in large cohorts is essential to dissect this heterogeneity. The Human Phenotype Ontology (HPO) provides a structured framework for capturing and comparing disease phenotypes. ObjectiveTo evaluate the implementation and outcomes of HPO-based phenotyping in CVID patients enrolled for whole-genome sequencing in a large national adult primary immunodeficiency cohort. MethodsWe developed a web-based Phenotype Capture Tool and delivered structured clinician training to standardise HPO annotation. Numerical laboratory parameters were mapped to corresponding HPO terms to enrich patient records. ResultsWe coded the phenotypes of 526 CVID patients across 11 UK centres. Clinician training increased phenotype granularity and improved phenotyping consistency between clinicians. We assigned 883 unique HPO terms across the cohort and applied logical rules to the terms to classify patients into an infection-only group and a complex phenotype group (42% vs 58%, respectively). Patients in the complex phenotype group were significantly more likely to have reduced switched memory and expanded CD21low B cells, as well as pathogenic variants in IUIS-listed genes overall and pathogenic NFKB1 variants specifically. Having a pathogenic variant in an IUIS-listed gene was associated with Autoimmune hemolytic anemia and having a pathogenic NFKB1 variant specifically was associated with Autoimmune neutropenia. ConclusionThis is the first study to systematically collect granular HPO-coded phenotypes in a large real-world CVID cohort, refining the CVID landscape and providing a comprehensive CVID HPO term set relevant for international research. Clinical ImplicationHPO allows systematic capture of CVID phenotypes with low inter-clinician variability and improves comparison of cohorts, enhancing identification of disease heterogeneity essential to support genotype-phenotype studies and targeted therapeutic strategies. Capsule summaryHPO-based phenotyping of 526 CVID patients improved annotation quality, identifying immunological and genetic associations with clinical manifestations, distinguishing infection-only from complex disease and refining clinical characterisation to support international collaboration.
Alfaro, H. E.; Lara-Arevalo, J.
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Ambulatory Care Sensitive Conditions (ACSCs) are conditions for which effective and timely primary health care (PHC) can prevent hospitalizations. They are widely used as a proxy indicator of access to and quality of PHC. Despite their relevance, evidence from Central America remains scarce. This study aimed to quantify the burden, describe the epidemiological profile, and assess temporal trends of ACSCs hospitalizations in Honduras from 2014 to 2024. We conducted a retrospective observational study using national administrative hospital discharge data from all Ministry of Health hospitals. ACSCs were defined using a standardized list of 20 diagnostic groups based on ICD-10 codes. We estimated percentages and sex-age-standardized hospitalization rates per 10,000 inhabitants. Clinical indicators included length of stay (LOS) and in-hospital fatality rates. Temporal trends were evaluated using joinpoint regression models to estimate annual percent changes (APC). Analyses included stratification by age, sex, and disease category. A total of 4,023,944 hospitalizations were analyzed, of which 547,486 (13.6%) were classified as ACSCs. The overall sex-age-standardized rate was 54.1 per 10,000 inhabitants. ACSCs standardized rates increased between 2014 and 2018 (APC: 2.7%; 95% CI: -2.4; 15.2), declined sharply between 2018 and 2021 (APC: -17.8%; 95% CI: -30.6; -10.3), and increased again between 2021 and 2024 (APC: 15.9%; 95% CI: 4.6; 37.6). Despite this rebound, rates remained below pre-pandemic levels. ACSCs were concentrated among children under 5 years (27.7%) and adults aged 60 years and older (29.9%). Noncommunicable diseases accounted for 56.8% of cases, with diabetes mellitus as the leading cause. Compared with non-ACSCs hospitalizations, ACSCs were associated with longer LOS (4.9 vs. 3.9 days; p <0.001) and higher in-hospital fatality rates (2.4% vs. 1.7%; p <0.001). ACSCs hospitalizations constitute a substantial burden in Honduras and reflect persistent gaps in PHC performance. Strengthening PHC resilience and capacity, particularly for chronic disease management and vulnerable populations, is essential to reduce avoidable hospitalizations and improve health system efficiency and equity.
Mahfouz, M.; Alzaben, E.
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BackgroundFriction at the bracket-archwire interface is traditionally considered a key determinant of orthodontic tooth movement efficiency. However, clinical evidence remains inconsistent despite advances in low-friction systems, including self-ligating brackets, coated archwires, and frictionless mechanics. ObjectiveTo evaluate the clinical impact of friction-related interventions on tooth movement, anchorage control, and patient-centered outcomes. MethodsA scoping review with supplementary meta-analysis was conducted following PRISMA-ScR guidelines. Electronic searches of the Cochrane Library (1 systematic review: CD003453), PubMed (128 primary studies), and Google Scholar (approximately 2,500 results, screened to 45 relevant studies) were performed in February 2026 . Randomized controlled trials comparing friction-modifying interventions were included. Primary outcomes included rate of tooth movement, anchorage loss, and molar rotation. Secondary outcomes included pain and treatment duration. Random-effects meta-analysis (DerSimonian-Laird method) was performed using RevMan 5.4; this method was chosen due to expected clinical heterogeneity . Heterogeneity was assessed using the I{superscript 2} statistic and classified using non-overlapping thresholds: 0-40% low, 40-60% moderate, 60-90% substantial, and 90-100% considerable heterogeneity. Risk of bias was assessed using Cochrane RoB 2, and certainty of evidence was evaluated using GRADE. Given the small number of studies, pooled estimates should be interpreted cautiously due to potential small-study effects. ResultsNineteen RCTs were included in quantitative synthesis. Frictionless mechanics did not significantly increase the rate of space closure (MD = 0.15 mm/month; 95% CI: -0.08 to 0.38; P = 0.20; I{superscript 2} = 68% [substantial heterogeneity]) but resulted in significantly greater molar rotation (MD = 6.1 degrees; 95% CI: 4.8 to 7.4; P < 0.001; I{superscript 2} = 45% [moderate heterogeneity]) . Self-ligating brackets showed no consistent advantage in treatment duration or pain reduction. Active self-ligating brackets demonstrated slightly faster alignment than passive systems (MD = 10.24 days; 95% CI: 2.80 to 17.68). Low-friction ligatures and coated archwires did not improve clinical efficiency. Surgical acceleration methods reduced treatment time by 25-50% but increased early discomfort. Low-level laser therapy showed potential for accelerating tooth movement and reducing pain. ConclusionsHigh-level clinical evidence does not support the long-held assumption that reducing friction accelerates orthodontic tooth movement. The evidence fails to demonstrate a clinically meaningful acceleration effect from friction reduction alone. Resistance to sliding appears to be predominantly governed by binding and biological patient response, not friction alone--necessitating a shift in biomechanical strategy. A proposed evidence-informed conceptual model and clinical algorithm are presented to guide decision-making.