Journal of Medical Virology
○ Wiley
Preprints posted in the last 30 days, ranked by how well they match Journal of Medical Virology's content profile, based on 140 papers previously published here. The average preprint has a 0.10% match score for this journal, so anything above that is already an above-average fit.
Mishra, P.; Mishra, S.; Srivastava, G.; Archana, K.; Siddiqi, M. I.; Haldar, S.; Tripathi, R. K.
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Japanese Encephalitis Virus (JEV) belongs to the Flavivirus family, and the RNA dependent RNA polymerase (RdRp) domain located at the C terminus of non structural protein 5 (NS5) regulates de novo viral genome synthesis. The conserved priming loop inserted in the thumb domain of RDRP initiates de novo genome synthesis. Interestingly, the reported replication process initiates with an interaction between NS5 (methyltransferase/RDRP) and NS3 (protease/helicase), and inhibiting this interaction directly correlates with the inhibition of viral replication. The function of the priming loop in the context of the NS5 NS3 interaction is not yet known. In this study, we studied the priming loop function in the NS5 NS3 interaction and viral replication. Using a structure based drug design approach, we screened the Maybridge compound library against the RdRp priming loop and identified 15 candidate compounds based on binding energy. Among them, DSHS00151 showed significant dose dependent inhibition of the NS5 NS3 interaction with an IC50 of 3.5 micromolar in the mammalian two hybrid assay, inhibited viral infectivity with an IC50 of 2.54 micromolar, and reduced viral RNA load with an IC50 of 2.9 micromolar, compared to CD10712. Molecular Dynamics (MD) simulations revealed that DSHS00151 exhibits stronger and more stable binding with the priming loop residues (790 to 812) compared to CD10712. The molecular mechanism suggested by the docking of the NS5 and NS3 proteins showed that the priming loop tends to rotate toward the NS3 protein to stabilize the complex, and compound binding restricts this loop rotation, thus compromising the stability of the NS5 and NS3 complex and affecting viral replication. Overall, our study validated the function of the NS5 priming loop as an allosteric site, and compounds binding to this allosteric site belong to the Non Nucleoside Reverse Transcriptase Inhibitors (NNRTI) class of inhibitors, which disrupt the NS5 and NS3 interaction and could be developed as novel anti JEV therapeutics.
Dinser, J.; Anft, M.; Wiemers, L.; Skrzypczyk, S.; Kohut, E.; Kurek, J.; Stervbo, U.; Seibert, F. S.; Westhoff, T. H.; Rosiewicz, K.; Babel, N.
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BackgroundPost-acute COVID-19 syndrome (PACS) can cause persistent disability involving fatigue, post-exertional malaise, neurocognitive symptoms, and autonomic manifestations. A clinically overlapping condition has been reported following COVID-19 vaccination and termed post-acute COVID-19 vaccination syndrome (PACVS), but its underlying mechanisms remain poorly understood. We investigated whether immune dysregulation, autoreactivity, antigen persistence, and viral reactivation--mechanisms implicated in PACS--are also present in PACVS. MethodsThis cross-sectional study included 28 PACS patients, 29 PACVS patients, and 16 convalescent controls (CCG). Clinical manifestations were assessed using ME/CFS-related symptom questionnaires and the Bell Score. T-cell phenotypes and T cells reactive to SARS-CoV-2 Spike, {beta}1/{beta}2-adrenergic receptor, and M3/M4 muscarinic receptor antigens were analyzed by multicolor flow cytometry. Circulating Spike protein and GPCR autoantibodies were quantified by ELISA, and EBV load by qPCR. ResultsPACS and PACVS showed substantial clinical overlap, although several symptoms were more severe in PACS. GPCR autoantibody profiles were comparable between patient groups, while {beta}2-adrenergic receptor autoantibodies were increased compared with CCG. Only three of 57 conventional immunophenotyping parameters differed between PACS and PACVS in unadjusted analyses, whereas both groups showed multiple alterations compared with CCG. Circulating Spike protein was detected in both patient groups, with the highest prevalence in PACVS. {beta}1/{beta}2- and M3/M4-reactive CD4+ T cells were increased, whereas Spike-specific CD4+ T cells were reduced compared with CCG. EBV reactivation was rare. ConclusionsPACS and PACVS exhibit substantial clinical and immunological overlap, including GPCR-directed autoreactivity and altered receptor-reactive T-cell responses. These shared immune-mediated features suggest overlapping pathophysiological mechanisms and warrant investigation of whether therapeutic strategies currently explored for PACS may also be relevant to PACVS.
Maust, B. S.; Griswold, K. A.; Khim, M.; Subramanian, S.; Staker, B.; Myler, P. J.; Kullin, B. R.; Happel, A.-U.; Varsani, A.; Jaspan, H. B.
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The Gardnerella genus includes a complex sub-taxonomy of bacterial species and subgroups which have been implicated in bacterial vaginosis. We analyzed G. leopoldii, G. swidsinski, G. piotii, and G. vaginalis genomes available in public databases and predicted proviral sequences using Cenote-Taker3. We clustered 266 prophage sequences into 140 viral genera level groupings that encode four distinct gene clusters and 19 different lysin proteins. Analysis of the bacterial and prophage sequence phylogenies reveals that while there were no specific prophage sequence lineages that infected each bacterial host, there is clustering of the prophage sequences by bacterial species within the Gardnerella genus.
Li, Y.-T.; Lin, Y.-T.; Chen, B.-S.; Kuo, C.-Y.; Huang, H.-Y.; Ko, H.-Y.; Huang, P.-Y.; Smith, G. J.; Lin, Y.-L.; Liu, M.-T.
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Low pathogenic avian influenza A(H7N7) virus detected in a poultry worker in Taiwan, 2026 was related to viruses circulating in Asian wild birds and possessed PB2 E627K, a mammalian adaptation marker. Enhanced surveillance for H7 viruses in poultry and rapid characterization of human cases are essential to assess pandemic potential.
Garcia-Gonzalez, E.; Sempere, J.; Llamosi, M.; Perez-Garcia, C.; Ubeda, A.; Sanchez-Honrado, A.; Agullo, L.; Ardanuy, C.; Perez-Fernandez, L.; Ocampo-Sosa, A.; Ramos-Sevillano, E.; Brown, J. S.; Domenech, M.; Yuste, J.
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Objectives: To evaluate the epidemiological evolution of unique pneumococcal serotypes covered by either PCV20 or PCV21, common serotypes by both vaccines and non-vaccine serotypes in adults. Methods: We characterized all national IPD clinical isolates from January 2009 to June 2026. Results: The highest burden of IPD was caused by serotypes shared between PCV20 and PCV21 with serotypes 3 and 8 the most prevalent in adults of all ages. During the pre-pandemic period, IPD caused by unique-PCV20 serotypes declined probably due to herd protection by paediatric vaccination with PCVs. In contrast, unique-PCV21 serotypes increased in incidence accounting for more cases than unique-PCV20 serotypes. However, after the COVID-19 pandemic, a different pattern was observed with unique-PCV20 serotypes increasing in incidence due a marked rise in IPD caused by serotypes 4 and 14 that has progressively reduced the gap in disease coverage. In adults aged 18-64 years, the fraction of disease that could be prevented with PCV20/PCV21 changed from 5% in favour of PCV21 (years 2022/2023) to 15% in favour of PCV20 (year 2026) whereas in adults [≥]65 years the vaccine contribution declined from 20% in favour of PCV21 (year 2022) to 8% in 2026. Conclusions: IPD trends in adults have changed after the COVID-19 pandemic, especially in recent years. Our study emphasizes the rapid re-emergence of infections caused by traditional PCV7 serotypes especially serotypes 4 and 14 and reinforce the idea that the use of broader PCVs must be accompanied by an increase in the uptake rates in adults of all ages.
Barbian, H. J.; Funk, M.; Black, S. R.; Hayden, M. K.; Zelencik, S.; Borah, B. F.; Zhang, D.; Bartlett, A. H.; Kociolek, L. K.; Rosenthal, A.; Farhat, N.; McSorley, V. E.; Kittner, A.
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In 2024, Chicago experienced a measles virus outbreak. Air samples collected as part of routine respiratory virus surveillance from three hospitals that received measles patients were retrospectively analyzed. Measles virus was detected in air samples from one emergency department across five weeks when measles patients were present and another when no known cases were present. Two of three viral sequences derived from air samples were identical to measles patients. The source of one diverging sequence could not be identified and may represent a case not identified by traditional surveillance methods. Air sampling may supplement measles investigation, surveillance and response.
Phacharoen, S.; Prawang, A.; Kanchanasurakit, S.; Phonphok, K.; Duangrithi, D.; Petchcharee, P.; Sangsanit, W.; Jintasataporn, R.
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Background/Aims: In medical practice, the rising prevalence of infections in kidney transplant recipients (KTRs) is a notable concern. However, understanding the incidence and risk factors associated with infections in KTRs remains limited. This study aims to assess the incidence and factors associated infection among KTRs. Additionally, we also investigate the median time of each infection among KTRs. Methods: A retrospective cohort study was conducted from 1 January 2018- 31 December 2022 at Thailand's tertiary hospital. We performed univariable and multivariable logistic regression analyses to identify potential risk factors related infection and investigated for the incidence and median time of each infection among KTRs. Results: A total of 179 participants were included in this study. Our findings reveal the kidney from living donor was protective factor for infection among KTRs (aOR 0.063, 95% CI 0.005-0.792; p = 0.032). Urinary tract infections (UTIs)showed as the predominant pathogenic manifestation among KTRs (43%). The median time of UTIs, cytomegalovirus (CMV) infection and pneumocystis pneumonia (PCP) were 16, 57 and 94.5 days, respectively. Conclusions: Our study establishes that receiving a kidney from a living donor is a protective factor against post-kidney transplant infections. Particularly urinary tract infections were most common of infection. Monitoring urinary tract infections post-transplantation is recommended. Moreover, awareness of UTI, CMV infection and PCP should be concerned during 2-3 months after transplantation. However, due to a small sample size; we recommend to increase the number of particular participants in further investigations.
Levine, M.; Beck, I. A.; Silverman, R. A.; Pepper, G.; Frenkel, L. M.
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In resource-limited settings plasma is usually transported to centralized laboratories for HIV RNA quantification; often by motor vehicles using dry ice. Any decay in plasma HIV RNA when near the threshold used to define virologic failure could impact clinical management. However, maintaining a cold chain during transport can be costly and limit the frequency of shipments, which can delay clinical assessments and also negatively impact patient care. Transporting plasma at ambient temperatures could facilitate timely measurements of plasma HIV RNA viral loads (VL). We conducted a stability study of HIV RNA in plasma held for 1, 3, 5, and 7 days at a range of temperatures (4{degrees}C, 30{degrees}C, and 37{degrees}C) to simulate the durations and temperatures specimens could experience during transport. Thirteen large volume plasma specimens with VL ranging from 2.7-5.53 log10 copies/mL were evaluated. Mean changes in VL between Day-0 to Day-1, Day-3, Day-5 or Day-7 were calculated, with decays >0.5 log10 c/mL considered clinically relevant. Compared to Day 0, the VL of plasma stored at 4{degrees}C and 30{degrees}C remained stable across the Days tested. The VL in plasma stored at 37{degrees}C had a progressive decline at Day-1, Day-3, Day-5 and Day-7 (means of -0.04, -0.19, -0.33. -0.34 log10 c/mL, respectively), with a decay of >0.5 log10 observed in 3/13 (23%) specimens at Day-7. A linear regression analysis showed that plasma specimens stored at 37{degrees}C significantly decayed over time (slope -0.054, 95% CI -0.079, -0.029; p=0.01). Any decay observed among specimens stored at 4{degrees}C and 30{degrees}C was not clinically relevant nor statistically significant. Our observations suggest that HIV RNA levels in plasma should remain stable if transported to centralized laboratories at ambient temperatures of [≤]30{degrees}C or chilled by cold packs over a period [≤]7 days. Transporting specimens with cold packs instead of dry ice could reduce costs and facilitate the timely monitoring of VL used to assess and guide antiretroviral therapy.
Sgarabotto, E.; Venkat, V.; Altan, E.; Gyzels, D.; Erdin, M.; Lehtinen, V.; Niamsap, T.; Greilich, S.; Valta, A.; Galan, M.; Firozpoor, J.; Eccard, J. A.; Jacob, J.; Imholt, C.; Sluydts, V.; Colombo, V.; Leirs, H.; McManus, A.; Stuart, P.; Gryseels, S.; De Bruyn, L.; Voigt, C. C.; Hoffmeister, U.; Alburkat, H.; Bourret, V.; Smura, T.; Castel, G.; Charbonnel, N.; Sironen, T.; Dutra, L. A. L.
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Recent zoonotic coronavirus outbreaks have sparked an interest in understanding coronaviruses circulating in animal reservoirs. While bats are recognised as major reservoirs for these viruses, coronaviruses have also been detected in a wide range of terrestrial small mammals, particularly rodents. However, coronavirus diversity in these mammals, specifically in Europe, is still poorly characterised. In this study, we detected and characterised coronaviruses in terrestrial small mammals and bats from Belgium, France, Germany, and Ireland. We screened tissue samples from rodents and shrews and environmental bat guano using pan-coronavirus real-time and conventional PCRs, with positive results confirmed by sanger sequencing. Among 2667 bat and 1152 terrestrial mammal samples, we detected 59 positive samples, 36 from bats and 23 from rodents, from which we recovered 60 coronavirus sequences, spanning both Alphacoronavirus and Betacoronavirus lineages. Through next generation sequencing we identified one Pipistrellus pygmaeus bat guano sample carrying two distinct alphacoronaviruses, representing Nyctacovirus and Pedacovirus subgenera. Among rodents, most coronavirus-positive samples originated from a zoo in Belgium, where several CoV lineages co-circulated. The identified rodent coronaviruses clustered among previously described rodent-associated lineages, some of which also include human and other mammal-derived coronavirus sequences. Consistent with previous studies, we found sarbecoviruses in horseshoe bats (particularly Rhinolophus ferrumequinum and R. hipposideros) and merbecoviruses in Plecotus auritus bats, and these viruses are distantly related to the human coronaviruses of the respective families. Similar to bat coronaviruses, some rodent coronaviruses strains seemed to be association with specific rodent species. In conclusion, our study enhances the understanding of coronaviruses in rodents and bats, revealing potential hotspots for these viruses and their implication for human and animal health. These findings underscore the necessity for continued surveillance of coronaviruses in wildlife reservoirs to mitigate future zoonotic spillover risks.
Espinosa-Parrilla, Y.; Fuentes-Guajardo, M.; Carvajal-Silva, L.; Aguilar-Valdes, K.; Signore, I. A.; Arevalo, T. V.; Zapata-Contreras, D.; Donoso, G.; Zuniga-Pacheco, P.; Valenzuela-Jorquera, H.; Rosso Villanelo, S. A.; Tobar-Calfucoy, E. A.; Yanez, C. E.; Carvajal, F.; Saez Hidalgo, J. M.; Sanhueza, S.; Quiroga, R. A.; Martinez, M. F.; Cerpa, L. C.; Varela, N. M.; Cappelli, C. L.; Campillay-Veliz, C. P.; Valdebenito-Maturana, B.; Garcia-Araya, J.; Santander, R. A.; Opazo, J.; Retamales-Ortega, R.; Bocchieri, P.; Alarcon, T. A.; Plaza, A.; Moraga, M.; Munoz, C. A.; Echeverria, C. A.; Dorador,
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Background: More than five years after the COVID-19 outbreak, the infection by the SARS-CoV-2 virus should still be considered as a global threat with highly heterogeneous clinical outcomes from asymptomatic to fatal depending on existing genetic and phenotypic inter-individual and inter-population variability. Our objective is to identify risk loci associated with COVID-19 in an admixed Latin American population. Methods: We performed a genome-wide association study in the framework of the Chilean C19-GenoNet team, analyzing a cohort of 3,417 individuals recruited from the northernmost to the southernmost regions of the country, who presented variations in the severity of their COVID-19 clinical manifestations. Results: Our investigation replicated the extensively reported association of several variants at the 3p21.31 locus with COVID-19 severity and found a suggestive association for a variant within the FOXP4 gene at 6p21.1 with COVID-19 hospitalization. Both associations appear to be shared with other populations. Importantly, our study identified three previously unreported loci associated with COVID-19 severity or hospitalization at 7q21.11, 16p13.12 and 6p25.3, and one additional locus at 4p13 associated with SARS-CoV-2 positivity, a proxy for infection susceptibility. Conclusions: these new risk loci may represent population-specific effects in Chilean and, potentially, other Latin American admixed groups. Our study highlights the importance of expanding efforts to study underrepresented and genetically different populations, which may provide new clues on the genetic basis of human diseases and may help to anticipate global responses to emerging viral infections and future pandemics.
Hoffmann, M.; Zhang, L.; Chen, N.; Moor, N.; Nehlmeier, I.; Graichen, L.; Moldenhauer, A.-S.; Dopfer-Jablonka, A.; Happle, C.; Behrens, G. M. N.; Poehlmann, S.
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SARS-CoV-2 continues to circulate globally at high levels and to evolve into new variants. Recently, a new saltation variant harbouring a highly mutated spike protein, PJ.2.1, emerged in North America. Here, we provide a brief epidemiological and virological characterization of PJ.2.1 and cocirculating variants. We report that PJ.2.1 is spreading in the USA, Canada, and Spain and mainly infects individuals aged 60 years and older, as do most other variants, with the exception of BA.3.2, which preferentially infects individuals aged 0-9 years. PJ.2.1 was less susceptible to inhibition by an antibody against ACE2 than were the other variants, indicating increased ACE2 binding. In contrast, PJ.2.1 did not show augmented evasion of antibodies from vaccinees who had received the LP.8.1-adapted vaccine compared with most other variants analysed. These results suggest that augmented ACE2 affinity rather than increased antibody evasion might drive the current, rapid spread of PJ.2.1.
Alvisi, A.; Casalini, A.; Mammana, L.; Ugolini, A.
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Background: Temporomandibular disorders (TMDs) are common conditions in the general population. Several therapeutic approaches are available, but there is no consensus on the most effective, particularly in physiotherapy. Objectives: To assess the efficacy of manual therapy (MT) and therapeutic exercise (TE) in reducing pain in patients with TMDs. Methods: Four databases (MEDLINE, PEDro, EMBASE, CINAHL) were searched up to March 2025. We included randomized controlled trials (RCTs) evaluating the effects of MT and/or TE in individuals with TMDs, compared to any other rehabilitation treatment, with pain intensity as the primary outcome. The methodological quality was assessed using the PEDro scale. A network meta-analysis was performed to compare the effectiveness of different rehabilitative approaches. Results: 25 RCTs for a total of 1,540 people were included. The main comparisons were: MT and/or TE vs no treatment or placebo, occlusal splint, and instrumental physiotherapy. In most studies, MT and TE were more effective than controls in reducing pain. However, the network meta-analysis indicated that multimodal treatments were the most effective. The methodological quality of the included studies ranged from 3 to 9 points. Conclusion: MT and TE are effective strategies for reducing pain in subjects with TMDs and should be used as first-line interventions before more invasive treatments; the combination of dry needling and manual therapy appears to be the most effective approach. Nonetheless, the variability in study quality suggests that further high-quality research is needed to confirm these findings.
Planas Pascual, B.; Bello, I.; Fernandez-Pinar, V.; Spiliopoulou, S. T.; Deu-Martin, M.; Ballesteros-Reviriego, G.; Berastegui-Garcia, C.; Ribas-Ball, M.; Gomez-Garrido, A.
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Frailty assessment is important while awaiting lung transplantation (LTx), as frailty is associated with disability and death before and after LTx. We assessed known risk factors and/or frailty indicators in frail, pre-frail, and non-frail patients according to the Short Physical Performance Battery (SPPB) and the Frailty Instrument for primary care of the Survey of Health, Ageing and Retirement in Europe (SHARE-FI), and evaluated the value of SHARE-FI as a proxy to detect frail patients. Frailty was assessed using SPPB and SHARE-FI in 82 patients on a waiting list for LTx. Demographic, anthropomorphic, and clinical variables were collected, and patients underwent respiratory/cardiorespiratory, biochemical, and quadriceps muscle performance assessments. The mean age was 57.3 {+/-} 9.4 years. Chronic obstructive pulmonary disease (COPD) (41.5%) and interstitial lung disease (ILD) (30.6%) were the most common indications for LTx. Four (4.9%), 13 (15.9%), and 65 (79.3%) patients were classified as frail, pre-frail, and non-frail by SPPB, respectively. These figures were 26 (31.7%), 41 (50%), and 15 (18.3%) with SHARE-FI. SPPB found differences between frail/pre-frail and non-frail patients in physical performance (6-minute walking distance) and muscular assessment, while SHARE-FI found differences in age, 6-minute walking distance, and oxygen saturation, and a trend in muscular strength. For COPD and ILD, frailty discrimination was better with SPPB. Concordance between the two measurements was weak, although all SPPB-frail ILD patients were detected by SHARE-FI. In patients awaiting LTx, SPPB showed better discrimination than SHARE-FI for COPD and ILD. SHARE-FI seems appropriate as a preliminary screening instrument for patients with ILD.
Nesaruddin, M.; Peya, F. I.; Rana, M. S.; Kabir, F.; Parvin, S. Z.; Dhar, S. S.; Islam, M. A.; Halder, P.
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Background: Long COVID can result in persistent functional limitations, pain, and fatigue after acute COVID-19. Evidence describing these outcomes among survivors in Bangladesh remains limited. This study assessed functional impairment, pain, and fatigue and explored factors associated with these outcomes among long COVID survivors in Bangladesh. Methods: This multisite cross-sectional study included 240 adults with a history of COVID-19. Functional status was assessed using the Post-COVID-19 Functional Status Scale. Pain and fatigue were assessed using the Brief Pain Inventory and Brief Fatigue Inventory, respectively. Descriptive statistics, Spearman correlation, and regression analyses were used to examine functional impairment and factors associated with pain and fatigue outcomes. Results: Functional limitations were common, with moderate limitation particularly frequent in basic activities of daily living, while slight limitation predominated across several other domains. Pain and fatigue measures showed significant correlations. Older age was associated with greater impairment in basic activities of daily living. Booster vaccination was associated with lower pain and fatigue scores, although the booster subgroup was small (n = 17). Tobacco non-use was also associated with lower scores across several pain and fatigue domains. Physiotherapy-related variables showed associations with some functional and symptom outcomes; however, these findings may reflect confounding by indication because participants with greater impairment or more complex symptoms may have been more likely to receive rehabilitation. Conclusions: Long COVID survivors in Bangladesh experience substantial and multidimensional functional, pain, and fatigue burdens. The findings support a comprehensive assessment that considers functional status, pain, fatigue, and participation together. Longitudinal studies with larger samples and standardized rehabilitation protocols are needed to clarify symptom trajectories, identify potentially modifiable factors, and evaluate the effectiveness of individualized rehabilitation interventions.
Hassane, F.; Lagare, A.; Yacouba, A.; Ousmane, H.; Issa, M.; Magagi, L. H.; Aoula, B.; Kaka, B. K.; Diallo, O.; Djedenam, M.; DOUTCHI, M.; Mamadou, S.
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Background: Hepatitis E virus (HEV) is highly endemic in several African countries with high mortality rate among pregnant women. The prevalence of HEV in Niger among pregnant women is unknown. We hereby aim to report the prevalence and risk factors of HEV among pregnant women in Niamey, Niger. Methods: Blood samples were collected from pregnant women attending antenatal consultation in three selected Health centers in Niamey. Data were collected for socio demographic characteristics using a structured questionnaire. Samples were tested using ELISA and qRT-PCR for anti- HEV IgM and RNA detection respectively. HEV associated risk factors were determined using multivariate logistic regression models. Results: A total of 491 pregnant women were enrolled with mean age of 26.5 years. The prevalence of anti-HEV IgM antibodies was 17.1%, while HEV RNA was detected in 3.46% of participants, indicating recent and active HEV infection. Anti-HEV IgM seropositivity was more frequent among women aged 26-30 years and those in the third trimester of pregnancy. Gravidity was significantly associated with HEV RNA positivity (p = 0.032). In multivariable analysis, the use of well water was independently associated with HEV infection (aOR = 75.70; 95% CI: 1.23-4643.20; p = 0.039). Conclusion: In view of the high seroprevalence of HEV among pregnant women, preventive measures including hygiene sensitization should be prioritized. Further studies should be conducted to assess the real impact of HEV infection on maternal and fetal health.
Lloyd-Evans, I.; Ford, M.; Hazzard, J.; Bartis, C.; Patel, F.; Roemer, N.; Wright, K.; Porter, K.; Coleman, M.; Galyov, E.; Megremis, S.; Clokie, M. R.; Millard, A. D.; Michniewski, S.; Wilkinson, R. C.
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Background: Klebsiella pneumoniae is a key causative agent of multidrug resistant nosocomial infections. Bacteriophages offer a promising alternative treatment, but the diversity of Klebsiella species requires the characterisation of a broad range of phages, particularly the poorly characterised jumbo phages. Materials and Methods: Phage BMCPR_005026 was isolated from sewage against Klebsiella pneumoniae. Whole genome sequencing, transmission electron microscopy and host range analysis against a diverse set of 40 clinically relevant Klebsiella strains were used to characterise the phage. Results: The virion had a myovirus morphology and genomic analysis placed it within an undefined family in Caudoviricetes where it forms a new species within the genus Alcyoneusvirus. BMCPR_005026 could form plaques on 3 of the 40 Klebsiella strains tested (7.5%) and formed halos. Conclusion: BMCPR_005026 represents a new species of phage within the genus Alcyoneusvirus with activity against 3 Klebsiella KL-types.
Lee, S. h.; Karimah, P. D.; KIM, K.; Kim, S. I.; Hwang, W. Y.; Kim, M. K.; Kim, J.-H.; Choi, C. H.; Lee, Y.-K.
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Objective: Current guidelines recommend different adjuvant treatment strategies for women with endometrioid early stage endometrial cancer exhibiting a p53 abnormal pattern. We aimed to evaluate recurrence patterns and explore the clinical implications for adjuvant therapy in this population. Materials and methods: This multicenter retrospective study included 86 patients with endometrioid, p53 abnormal, FIGO stage I, II endometrial cancer treated between 2013 and 2023 at six hospitals in the Republic of Korea. Clinicopathologic data were collected through medical record review. Progression free survival (PFS) was estimated using the Kaplan Meier method, and prognostic factors were analyzed using Cox proportional hazards regression models. Results: The 12, 24, and 36 month PFS rates were 91%, 78%, and 76%, respectively. Among the 16 patients who experienced recurrence, 12 (75%) had distant metastases. Adjuvant chemotherapy showed a trend toward improved PFS compared with adjuvant radiation therapy with or without chemotherapy (p=0.10). In multivariable analysis, the p53 overexpression pattern was independently associated with worse PFS compared with the p53 null pattern (HR 8.59, 95% CI 1.61 to 45.79, p=0.01). Conclusion: Given the poor PFS, the predominance of distant recurrence and the observed trend toward improved PFS with chemotherapy, adjuvant chemotherapy may be considered in women with endometrioid early stage endometrial cancer exhibiting a p53 abnormal pattern. Further studies are warranted to clarify the prognostic impact of p53 abnormality subtypes.
Lambert, B. L.
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Background. Regulatory pressure to avoid confusingly similar drug names appears to have pushed manufacturers to coin more distinctive proprietary names, but no one has quantitatively analyzed this trend. Objective. To determine whether proprietary drug names became more orthographically distinctive (unusual in spelling) over time. Methods. We examined 1,321 US Food and Drug Administration (FDA) new molecular entity (NME) names (1985-2024), 2,769 FDA Orange Book trade names (1982-2026), 177,337 US pharmaceutical trademarks (1980-2026), and 1,273 generic names (1982-2025). Compared to prior names (including those already marketed) and ordinary English, we scored each name's character trigram (three-letter sequence) surprisal (statistical unexpectedness) and its edit-distance similarity to the closest existing names. Linear regression tested time trends, controlling for name length. Results. Mean NME trigram surprisal rose in every decade between the 1980s and 2020s, from 7.21 to 8.50 nats (natural-logarithm units, higher meaning less predictable), an 18% increase (b = 0.038, p < .001, R2 = 0.34). Half of 2020s names (7% in the 1980s) contained a letter sequence found in no common English word (e.g., Jesduvroq, Omvoh). Nearest-neighbor similarity fell after the early 1990s. Trademark data showed the same trend (b = 0.016, p < .001). Generic names showed a weaker trend (b = 0.011, R2 = 0.063). Conclusions. Over four decades, drug names became more orthographically distinctive, consistent with namespace crowding, deliberate efforts to avoid confusing names, and branding strategy. Because unfamiliar letter sequences can introduce other error pathways, increased distinctiveness does not necessarily imply improved safety.
Mandal, S.; Majumder, S.; Nandy, S. K.; Mukherjee, R.; Giri, K.; Mukhopadhyay, A.
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Vertical transmission of SARS-CoV-2 is controversial. Owing to the low expression of ACE2 along with TMPRSS2 in placenta, role of secondary receptors becomes significant. In our study we predicted twelve interactors of spike protein expressed in placenta through interactome analysis followed by docking and molecular dynamic simulation. Three interactors of SARS-CoV-2 spike protein were found to be CD147, EGFR and LDLR. Expression at transcriptomic and translational level by real-time PCR and immunohistochemistry respectively was observed in placenta samples obtained from women with COVID exposure risk and compared to control. Elevated protein levels of CD147 (OR=14.667), ACE2 (OR=8.25) and LDLR (OR=1.9) was associated with higher exposure risk. However, the variation in mRNA expression was not statistically significant. Computational study showed that CD147/basigin, EGFR and LDLR stably interact with spike protein outside its primary receptor binding domain. In-vitro binding assay confirmed the physical interaction between spike protein and the placental receptors. In-silico site-directed mutagenesis further identified key potential binding hotspots of spike protein- Tyr28 and Trp64 for CD147, Phe643, Val642, Thr632 for LDLR and Leu8, Phe59, Phe32, Tyr28, Trp64, Trwp152, His245, and Val213 for EGFR. Finally, concluded that CD147, EGFR and LDLR might act as secondary non-canonical cofactors for SARS-CoV-2 spike protein in placenta, thereby increasing its susceptibility and tissue tropism. The study overall gives a better insight into potential placental suscpetibility providing targeted therapeutic opportunities.
Govindarajan, R.; Gowri Sankar, S.; Rahi, M.; Philip Samuel, P.; Alwin Prem Anand, A.
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Orientia tsutsugamushi is the causative agent of scrub typhus infection in humans. This pathogen is transmitted into mammalian hosts including humans through Leptotrombidium mites. Till date, detection of O. tsutsugamushi in human was performed using PCR assay with 56kDa type specific antigen (TSA56), 47kDa outer membrane protein (47kDa-OMP) and groEL chaperonin gene. To understand the efficiency of different genes for the detection of O. tsutsugamushi in Leptotrombidium mites, we performed a comparative PCR assay with various universal primers targeting different genes including TSA56, 47kDa-OMP and groEL gene. We have collected 500 Leptotrombidium mites from Vellore, Tamil Nadu and, the mites were segregated into 50 pools with 10 mites in each pool were used for DNA extraction. The molecular detection of O. tsutsugamushi was performed using PCR assays (including conventional, nested and duplex PCR). The comparative PCR analysis showed nested PCR of groEL gene has high efficiency in detecting the presence of O. tsutsugamushi in chigger samples compared to other genes. Interestingly, groEL target demonstrated high efficiency for detection of O. tsutsugamushi in chigger samples and, when used with nested primers, can facilitate differentiation of O. tsutsugamushi from other rickettsial pathogens. Thus, we conclude groEL gene nested PCR assay can be used routinely to detect O. tsutsugamushi in trombiculid mites.