bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic and histological assessment in first-degree relatives of gastric cancer patients undergoing gastroscopy: a cross-sectional study
Authors: Ligato Irene , Dilaghi Emanuele , Cozza Giulio , Scalamonti Silvia , Pilozzi Emanuela , Panzuto Francesco , Lahner Edith , Esposito Gianluca
Published: February 2025

Background

First-degree relatives of gastric cancer (GC) patients are known to have an increased risk of developing GC. However, guidelines in low-intermediate incidence regions often lack specific recommendations for managing both asymptomatic and symptomatic relatives at risk.

Aim

This study aimed to evaluate the differences in relevant histological findings (e.g. Helicobacter pylori infection, gastric precancerous and neoplastic conditions) between asymptomatic patients undergoing esophagogastroduodenoscopy due to first-degree relatives with GC and patients with symptoms or other clinical indications and presence of first-degree relatives with GC. The secondary aim was to identify the patient’s risk factors of relevant histological findings.

Methods

This single-center retrospective study included patients undergoing esophagogastroduodenoscopy with biopsies with the indication for first-degree relatives with GC from January 2008 to September 2022. They were analyzed in two groups based on whether they had additional symptoms or clinical indications for esophagogastroduodenoscopy.

Results

Overall, 283 patients were included (54.5% asymptomatic vs. 45.5% symptomatic). Histological findings that led to changes in patient management were identified in 32% of cases. No significant differences in histological findings between the two groups were observed (P = 0.077). A subanalysis revealed that patients with male relatives affected by GC had a higher incidence of relevant histological findings than those with female family members with GC (P = 0.013) with an odds ratio of 3.10.

Conclusion

First-degree relatives of GC patients may be at risk for H. pylori infection and gastric precancerous conditions regardless of symptoms or other indications, and a proactive endoscopic screening could be considered even in countries with low GC incidence.
Analysis of noninvasive methods in chronic hepatitis/human immunodeficiency virus mono- and co-infected patients with advanced fibrosis
Authors: dos Santos Deise Machado , Penteado Júlia Oliveira , Nader Maiba Mikhael , Basso Rossana Patrícia , da Silva Naylê Maria Oliveira , Quiche Lara Carolina Peixoto , Borges Mariana Penteado , Gehres Luiz Felipe Silveira , Hoffmann Tchurle , Rodrigues Leandro Farias , da Silva Júnior Flavio Manoel Rodrigues
Published: February 2025

Objectives

The aim of this study was to evaluate the degree of advanced fibrosis (F3/F4) using noninvasive methods [elastography, Fibrosis-4 (FIB4), and aspartate aminotransferase to platelet ratio index (APRI)] before and after treatment with new direct-acting antiviral agents (DAAs) in patients with hepatitis C virus (HCV), both in cases of co-infection (HCV/HIV) and single infection (HCV).

Methods

This is a longitudinal study involving patients with HCV who are co-infected with HIV, who initiated HCV treatment between a positive anti-HCV test for more than 6 months and detectable HCV RNA. The control group consisted of patients with HCV infection without HIV co-infection, who received treatment during the same period as the co-infected patients.

Results

A total of 75 co-infected and 87 mono-infected HCV patients were eligible. Before treatment, elastography and FIB4 methods showed a strong agreement (0.73), while after treatment, the agreement was moderate (0.58). Between elastography and APRI, a strong agreement was observed before treatment (0.66) and fair/weak agreement after treatment (0.30). Both FIB4 and APRI showed perfect agreement at both time points with values above 0.9 (0.97 for pretreatment and 0.92 for posttreatment). The use of DAAs was associated with high rates of sustained virological response and reduction in fibrosis degrees in the posttreatment period, as assessed through biomarkers and hepatic elastography.

Conclusion

The utilization of biomarkers in clinical practice for assessing hepatic fibrosis is an essential tool. Thus, for an accurate evaluation of hepatic fibrosis, particularly after HCV treatment, the use of elastography, rather than biomarkers alone, is more appropriate.
Sterile systemic inflammation reaction associated with 90-day mortality in patients with HBV-related acute-on-chronic liver failure
Authors: Chen Jing , Liu Xiaoyan , Guan Chongdan , Peng Yuhui , Li Chen , Yan Lilong , Ning Peng , Hu Jinhua , Su Haibin
Published: February 2025

Background

Acute-on-chronic liver failure (ACLF) represents the terminal and most lethal phase of acute decompensated cirrhosis. Systemic inflammation plays a critical role in the pathogenesis of ACLF. Systemic inflammation reaction syndrome (SIRS) is a marker of ongoing inflammation. Therefore, we aim to evaluate the relationship of sterile SIRS with hepatitis B virus (HBV)-related ACLF (HBV-ACLF).

Methods

HBV-ACLF patients with sterile SIRS who were hospitalized between December 2016 and December 2018 were retrospectively analyzed. All patients were followed up until 90 days. Risk factors associated with 90-day mortality and sterile SIRS development were assessed.

Results

Among 151 HBV-ACLF patients without infection, 37 patients (24.5%) presented with or developed sterile SIRS. During the 90-day follow-up, 23 of the 37 patients with sterile SIRS died (62.2%), compared to 40 patients without sterile SIRS (35.1%, P = 0.004). Univariate analysis showed that age, total bilirubin (TBIL), international normalized ratio, ammonia, presence of sterile SIRS, model for end-stage liver disease score, presence of complications, and organ failures were associated with 90-day mortality. In multivariate analyses, the presence of sterile SIRS was an independent risk factor for 90-day mortality. Among SIRS components, heart rate (HR) was the most frequently met criterion (56 patients, 37.09%). Patients who met the HR or temperature criterion had lower 90-day survival rate than those who did not (46.4 vs 65.3%, P = 0.020; 16.7 vs 60.0%, P = 0.020).

Conclusion

The presence of sterile SIRS in HBV-ACLF patients was closely associated with prognosis.
Claudin-2 simplifies histological assessment of activity/remission of ulcerative colitis in real-life daily practice
Authors: Bassotti Gabrio , Del Sordo Rachele , Lanzarotto Francesco , Mino Sara , Ricci Chiara , Villanacci Vincenzo
Published: February 2025

Objectives

Mucosal healing, and in particular histological mucosal healing, represents the new frontier as a treatment goal for inflammatory bowel diseases. However, the assessment of mucosal healing is presently somewhat limited by the numerous pathological scores available, and the lack of a global consensus on how to best assess it. For this reason, the availability of a simple and rapid test to evaluate the inflammatory state of the mucosa after treatment would be useful, especially for the daily routine.

Methods

To exploit the above purpose, we evaluated the possible usefulness of antibodies against claudin-2, a protein of intestinal epithelium tight junctions, as a possible test to assess the presence of activity in ulcerative colitis following treatment. Biopsies from 28 patients with distal localization of the disease and clinical and endoscopic remission were tested for claudin-2 reactivity.

Results

Claudin-2 reactivity was always negative in noninvolved segments and displayed a variable staining intensity in concordance with the histological activity. There was a highly significant (P < 0.0001) correlation between histological score and claudin-2 expression in the colonic segments involved (descending, sigmoid colon, and rectum).

Conclusions

Our results suggest that the use of claudin-2 in the routine daily practice could simplify and corroborate the results of current histological evaluations, especially in clinical practice and posttreatment follow-up.
Cardiovascular events and incident diabetes in 220 patients with MASLD according to basal liver fibrosis: a 10-year follow-up historic cohort
Authors: Choque Vargas Cinthia , Cáceres Francisco , Landeira Graciela , Perez Soledad , Marchi Laura , Ruffillo Gabriela , Tevez Silvina , Puga-Tejada Miguel , Fassio Eduardo
Published: February 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) patients have a higher incidence of cardiovascular events (CVE) compared to controls.

Aim

The aim of this study is to analyze association between liver fibrosis with CVE, incident diabetes, and cirrhosis complications.

Methods

Historic cohort of biopsy-proven MASLD patients, divided into two groups: F0–F2 vs F3–F4 fibrosis. Baseline data included metabolic traits and liver function tests. Patients were contacted and scheduled for laboratory analysis and elastography. Endpoints were (a) CVE, defined as any of acute myocardial infarction, coronary stenting, ischemic cardiopathy, and stroke; (b) incident diabetes; (c) cirrhosis complications. Baseline data were collected at the time of liver biopsy, while follow-up data were recovered through personal interview or medical records. A stepwise logistic regression determined predictive variables for each endpoint.

Results

Study population included 220 patients with median age 53 years, and 145 were women; baseline fibrosis was F0–F2 in 165 patients and F3–F4 in 55 patients; median follow-up was 9.9 years. A higher percentage of F3–F4 patients had CVE (29.4%) than F0–F2 ones (13.1%) (hazard ratio 2.42; 95% CI: 1.26–4.6; P = 0.008). Incident diabetes occurred in 53.3% of F3–F4 and 20.2% of F0–F2 cohort (hazard ratio 3.04; 95% CI: 1.99–4.86; P < 0.001); cirrhosis complications occurred in 9/55 F3–F4 patients and in 1/165 F0–F2 ones (hazard ratio 26.3; 95% CI: 3.3–208.3; P = 0.002). Multivariate analysis confirmed liver fibrosis as an independent predictor of incident diabetes and cirrhosis complications. CVE were associated with baseline diabetes and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio.

Conclusion

In a cohort of 220 MASLD patients followed for 9.9 years, baseline F3–F4 was associated with incident diabetes and cirrhosis complications. AST/ALT ratio and diabetes were associated with CVE.
The use of oral antibiotic cocktail in medically refractory paediatric acute severe colitis: a case series
Authors: Morgan Manal , Loel Benjamin , Lang Ray , Reilly Claire , Balouch Fariha , Burgess Chris , Thapar Nikhil , Lewindon Peter
Published: February 2025

Objective

Paediatric acute severe colitis (ASC) is a life-threatening gastroenterological emergency and a predictor of poor long-term inflammatory bowel disease outcomes. We report our experience with oral antibiotic combination therapy as rescue therapy for children with ASC failing to respond to conventional medical therapy (CMT).

Methods

We analysed data of children admitted with ASC between January 2020 and January 2023 who failed steroids and infliximab and received the oral antibiotic combination therapy (vancomycin, amoxicillin, metronidazole and doxycycline). Treatments and responses including Paediatric Ulcerative Colitis Activity Index (PUCAI), biochemical markers, intestinal ultrasound (IUS) and colectomy rates (acute and deferred) were collated.

Results

Oral antibiotic combination therapy was prescribed in 12 episodes of ASC in 11 children following failure of CMT. Improvements were seen in PUCAI (mean difference = −27.86, 95% confidence interval = −43.43 to −12.28, P < 0.001), albumin (mean: 29.5–33.6) and CRP (mean: 12–4), as well as in IUS (bowel wall thickening, extent of involvement or vascularity in five of seven). Five of 11 children were colectomy free at a maximum follow-up of 24 months. Three children had acute colectomy during index admission and three underwent deferred colectomy at a mean of 4 months.

Conclusion

Oral antibiotic combination therapy shows promise in deferring and, in some cases, averting the need for acute colectomy in medically refractory ASC. This notable finding warrants confirmation in larger studies.
An Integrative Review of Quality Improvement Competence and Engagement Among Frontline Nurses
Authors: Chang Jung-Hsin , Tschannen Dana
Published: February 2025

Background:

Nurses providing direct care have firsthand knowledge of gaps in practice and thus must actively engage in quality improvement (QI) to enhance patient outcomes.

Purpose:

This integrative review evaluated QI competence and engagement among frontline nurses.

Methods:

Using Souza et al’s 6-step framework, literature on QI engagement and competence was synthesized using a rigorous search strategy and quality assessment.

Results:

Sixteen studies revealed generally low QI engagement and competence. Factors such as education, experience, and role influenced engagement, with higher levels of education and experience linked to higher QI involvement. Nurse leaders had higher engagement, underscoring the need for strong leadership in creating a culture of improvement.

Conclusions:

Successful and sustainable QI programs and supportive environments enhance QI engagement and competence among frontline nurses.
Diagnostic Accuracy of Transvaginal Ultrasonography for Endometriosis According to the International Deep Endometriosis Analysis Consensus
Authors: Mick Ido , Freger Shay M. , Marien Melissa , Gholiof Mahsa , Leonardi Mathew
Published: February 2025

OBJECTIVE:

To evaluate the diagnostic accuracy of transvaginal ultrasonography (TVUS) in detecting deep endometriosis, ovarian endometriosis, and superficial endometriosis using the IDEA (International Deep Endometriosis Analysis) consensus and novel International Terminology definitions for endometriosis phenotypes.

METHODS:

This prospective diagnostic accuracy study was conducted at McMaster University from November 2021 to January 2023. Participants included 125 individuals aged 18–50 years with suspected endometriosis who were undergoing TVUS followed by laparoscopic surgery. The index test, TVUS, was performed in accordance with the IDEA consensus, with results compared with laparoscopy and histopathologic findings, which served as the reference standard. Deep endometriosis was defined as endometriosis with any depth of infiltration, and superficial endometriosis was defined as endometriosis without any infiltration beyond the peritoneal surface. Diagnostic accuracy metrics, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated.

RESULTS:

The study demonstrated high diagnostic accuracy for endometriomas and deep endometriosis with TVUS, achieving a sensitivity of 95.0% for left ovarian endometrioma, 94.9% for right ovarian endometrioma, and sensitivity ranging from 84.3% to 100% for various deep endometriosis sites. Transvaginal ultrasonography showed high specificity for endometriomas (98.9%) and deep endometriosis (range 97.0–100%). However, TVUS showed lower sensitivity for superficial endometriosis (range 4.0–43.5%) but high specificity (99.0–100%) and PPV (90.0–100%). The accuracy of detecting superficial endometriosis improved when cases with ovarian endometriosis, deep endometriosis, and pouch of Douglas obliteration were excluded.

CONCLUSION:

Transvaginal ultrasonography demonstrates robust diagnostic accuracy for deep endometriosis and ovarian endometriosis, reaffirming its utility as a first-line diagnostic tool in endometriosis management despite changes in definitions of deep endometriosis and superficial endometriosis. However, its sensitivity for superficial endometriosis remains limited, suggesting the need for additional diagnostic techniques or refined ultrasound approaches for accurate detection of superficial endometriosis. The findings support the integration of TVUS in clinical practice while highlighting the need for further advancements in diagnosing superficial endometriosis to mitigate diagnostic delays.
Sepsis in Critically Ill Children in Bolivia: Multicenter Retrospective Evaluation of the Phoenix Criteria for Sepsis in a 2023 Cohort
Authors: Copana-Olmos Raul , Casson-Rodriguez Nils , Diaz-Villalobos Willmer , Urquieta-Clavel Victor , Tejerina-Ortiz Mary , Mendoza-Montoya Carol , Fernandez-Vidal Maricruz , Forest-Yepez Mariel , Blanco-Espejo Danny , Rivera-Murguia Ibeth , Castro-Auza Claudia , Gamboa-Lanza Milenka , Paco-Barral Jhovana E. , Choque-Osco Gustavo , Vera-Dorado Betzhi , Cuellar-Gutierrez Magbely , Sarmiento-Zurita Alan J. , Carrillo-Vargas Michelle G. , Ledezma-Hurtado Brisa W. , Sanchez-Pinto L. Nelson
Published: February 2025

Objectives:

We evaluated the Phoenix criteria and the Phoenix Sepsis Score in a multicenter retrospective cohort of critically ill children with a clinical diagnosis of sepsis or septic shock in Bolivia. In addition, we aimed to assess whether management in a PICU at high altitude in the Bolivian Andes was associated with the performance of the respiratory dysfunction component in the Phoenix Sepsis Score.

Design:

Multicenter retrospective cohort study.

Setting:

Fourteen PICUs in Bolivia.

Patients:

Children admitted to the PICU with a clinical diagnosis of sepsis or septic shock from January 2023 to December 2023.

Interventions:

None.

Measurements and Main Results:

There were 273 patients with a diagnosis of sepsis in 2023, of which 257 (94.1%) met the 2024 Phoenix criteria for sepsis, and 166 (60.8%) met the systemic inflammatory response syndrome (SIRS)-based criteria for sepsis. Among the 257 patients meeting Phoenix sepsis criteria, 86 died (33.5%). Of the patients with Phoenix-based sepsis, there were 100 of 257 (38.9%) who were SIRS-negative, and 27 of 100 died (27.0%). After correcting the oxygenation indices for altitude, 149 of 273 patients (54.6%) had a lower Phoenix respiratory score and an associated mortality more consistent with the expected mortality of the newly derived subscore. Patients at higher altitudes had higher hemoglobin levels and higher estimated oxygen carrying capacity, and these data were independently associated with lower odds of mortality after controlling for altitude-corrected Phoenix score.

Conclusions:

In this 2023, retrospective cohort of PICU patients with sepsis in Bolivia, we have found that the majority met the 2024 Phoenix sepsis criteria, but less than two-thirds met the SIRS-based criteria for diagnosis. However, the respiratory score in the Phoenix criteria overestimated the severity of respiratory dysfunction in more than half of the cohort, likely because the score does not take account of the Andean adaptation to high altitude, with higher oxygen carrying capacity.
Cardiac Point-of-Care Ultrasound Findings in Multisystem Inflammatory Syndrome in Children in the Pediatric Emergency Department
Authors: Kestenbom Inbal , Scheier Eric , Daviko Bat-Hen Annie , Berant Ron , Buchshtav Nachshon , Sheinberg Natalia , Friedman Nir ,   On Behalf of the Israeli PEM POCUS Group
Published: February 2025

Objectives:

Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening condition associated with cardiac involvement. Cardiac point-of-care ultrasound (POCUS) can be performed at the bedside in the pediatric emergency department (PED) to identify cardiac pathology. There is limited data on cardiac POCUS findings in children with MIS-C in the PED. The main outcome objective of our study was to describe the cardiac POCUS findings in MIS-C patients in the PED.

Methods:

This is a multicenter, retrospective, cohort study between February 15, 2021 and March 31, 2022, during the alpha, delta, and omicron severe acute respiratory syndrome coronavirus 2 waves in 6 PEDs in Israel. We included patients diagnosed with MIS-C who received a cardiac POCUS examination in the PED. All POCUS clips were analyzed by a PED POCUS expert.

Results:

We included 32 MIS-C patients who underwent cardiac POCUS during the study period. The median age was 8 years (interquartile range = 6 to 10 y), and 20 (63%) were males. The median time from onset of symptoms upon PED visit was 5 days (interquartile range = 4 to 5 d). Overall, 27 patients (84%) were diagnosed with normal cardiac function and 5 patients with decreased cardiac function (16%). No patients were diagnosed with pathologic cardiac effusion. Three patients were diagnosed with plethoric inferior vena cava. Among the patients, 17 (53%) were admitted to the pediatric wards and 15 (47%) to the pediatric intensive care unit. There was no mortality.

Conclusion:

Cardiac POCUS by PEM physicians is an applicable tool for the evaluation of MIS-C patients in the PED. In our study, 16% of MIS-C patients who underwent POCUS had decreased cardiac function per POCUS on their PED presentation. Future studies are needed to evaluate the impact of cardiac POCUS in the PED of patients with MIS-C.
A Prediction Rule to Identify Children and Young Adults at Low Risk for Myocarditis
Authors: Genadry Katia C. , Monuteaux Michael C. , Michelson Kenneth A. , Bucholz Emily M. , Mannix Rebekah
Published: February 2025

Objective:

(1) To derive a prediction rule for pediatric myocarditis that distinguishes low-risk patients for whom additional work-up, including venipuncture or cardiac imaging, may be avoided, (2) to assess the test characteristics of troponin in our study population.

Methods:

This retrospective case-control study included all patients who presented to a pediatric emergency department between 2010 and 2021 and underwent troponin testing for suspected myocarditis. Myocarditis cases (identified using American Heart Association criteria) and controls were to approximate a 1:2 ratio. Logistic regression with forward selection was used to derive a prediction rule for myocarditis. As the goal was to derive a rule for low-risk children, in whom venipuncture would be unnecessary, laboratory results were analyzed separately.

Results:

We identified 93 case patients and 202 control patients. The final prediction rule included chest pain [adjusted odds ratio (aOR): 3.5, 95% CI: 1.8 to 7.0], reported or measured fever (aOR: 1.7, 95% CI: 1.0 to 3.1,) and atrioventricular conduction delays or ST segment changes (aOR: 2.6, 95% CI: 1.4 to 4.7). Sensitivity, calculated as the proportion of cases with at least one of the 3 predictors was 99% (95% CI: 0.94 to 0.99), and specificity was 14% (95% CI: 0.09 to 0.20). With at least 2 predictors, sensitivity was 60% (95% CI: 0.50 to 0.71) and specificity was 72% (95% CI: 0.65 to 0.78).

Conclusion:

The prediction rule developed can help identify children at low risk for myocarditis and, therefore, avoid troponin testing and/or further evaluation including cardiology consult or cardiac imaging. Specificity was insufficient to rule in myocarditis without additional investigation.
Single Doses of Pediatric Dolutegravir-Dispersible Tablets in Neonates Support Multi-Dosing: PETITE-DTG Study
Authors: Cressey Tim R. , Salvadori Nicolas , Rabie Helena , du Toit Samantha , Than-in-at Kanchana , Groenewald Maria , Capparelli Edmund , Owen Andrew , Cressey Ratchada , Lallemant Marc , Cotton Mark F. , Bekker Adrie
Published: February 2025

Background:

Dolutegravir dispersible tablets (DTG-DT) are approved for infants ≥4 weeks and ≥3 kg but their suitability for neonates remains unknown.

Methods:

PETITE-DTG is a Phase I/II, open-label, single center, two-stage trial in South Africa to evaluate the pharmacokinetics (PK) and safety of DTG in term neonates of pregnant individuals receiving DTG-based therapy. In Stage 1, neonates on standard antiretroviral prophylaxis received a single dose of 5 mg DTG-DT between ≥14 and <28 days of life (Cohort 1A); or <14 days of life (Cohort 1B), followed by PK and safety assessments. A population PK model was developed and multi-dose scenarios simulated [DTG targets: geometric mean (GM) Ctau>0.67 µg/mL and Cmax<17.0 µg/mL].

Results:

16 neonates, 8 per cohort, completed Stage 1. Median (range) birth weight was 3.1 (2.6-4.2) kg and PK sampling was performed between 3-22 days of life. No Grade 3 or higher adverse events were observed. DTG clearance was influenced by body weight and postnatal age. Simulations predicted that >10% of neonates would have a Cmax>17.0 µg/mL with DTG once daily (q24) during the first 2 weeks of life. Administration of DTG every 48 hours (q48) from day 1-14 of life, followed by DTG every 24 hours through day 28, predicted a GM Ctau between 0.86-4.35 µg/mL; 98% with a Cmax<17.0 µg/mL.

Conclusions:

Due to the slow postnatal DTG clearance after birth, a multi-dose strategy of 5 mg DTG-DT q48 for the first 2 weeks of life, followed by q24 through 28 days, was selected for assessment in Stage 2.
THE ASSOCIATION BETWEEN HIV-RELATED STIGMA, ART ADHERENCE AND CARDIOVASCULAR DISEASE RISK IN PEOPLE LIVING WITH HIV.
Authors: Shilabye Patane S. , Scheuermaier Karine , Vos-Seda Alinda G. , Barth Roos E. , Devillé Walter , Coutinho Roel A. , Umunnakwe Chijioke J. , Grobbee Diederick E. , Venter Francois , Tempelman Hugo , Klipstein-Grobusch Kerstin
Published: February 2025

Introduction:

HIV/AIDS continues to be a significant health issue in Sub-Saharan Africa, with stigma likely affecting ART adherence, and subsequently viremia, inflammation, and cardiovascular disease (CVD). We investigated the association between stigma, ART adherence, and CVD risk among people living with HIV (PLWH).

Setting:

A longitudinal study was conducted among 325 PLWH from the Ndlovu Cohort Study, South Africa.

Methods:

Stigma was assessed using a 12-item questionnaire (range: 0-44; higher scores indicate greater stigma). Pulse wave velocity (PWV, CVD surrogate marker) and viral load (VL) were assessed at 12 and 36 months. VL was considered a surrogate marker of ART adherence: VL>1000 copies indicating poor/no adherence, VL 50-1000 copies suboptimal, and VL<50 copies good adherence. The relationship between stigma, VL, and PWV, was assessed by linear regression and changes in PWV overtime by mixed linear models.

Results:

At baseline, PLWH (n=325, mean age (SD)=41.1 (10.2) years, 67% female) had mean PWV of 7.3m/s. Good, suboptimal, and poor adherence were 78%, 15%, and 7%, respectively. Mean (SD) stigma score was 16.9 (1.4) and was not associated with viral load and PWV. Suboptimal and poor adherence were associated with higher PWV [Beta=4.18 (95%CI 1.79_6.57)] at 12 months and between 12 and 36 months [Beta=1.30 (95%CI 0.06_2.55)] in mixed model analyses in PLWH>49 years, respectively. PWV increased by 0.21m/s (95%CI 0.02_0.40; p=0.03) between 12 and 36 months overall.

Conclusion:

In this study, poor ART adherence was associated with higher PWV. Stigma score was low and not associated with ART adherence and PWV.
Mathematically tractable models of random phylogenetic networks: an overview of some recent developments
Authors: Bienvenu François
Published: February 2025

Models of random phylogenetic networks have been used since the inception of the field, but the introduction and rigorous study of mathematically tractable models is a much more recent topic that has gained momentum in the last 5 years. This manuscript discusses some recent developments in the field through a selection of examples. The emphasis is on the techniques rather than on the results themselves, and on probabilistic tools rather than on combinatorial ones.

This article is part of the theme issue ‘“A mathematical theory of evolution”: phylogenetic models dating back 100 years’.
Speciation completion rates have limited impact on macroevolutionary diversification
Authors: Veron Pierre , Andréoletti Jérémy , Giraud Tatiana , Morlon Hélène
Published: February 2025

Standard birth–death (BD) processes used in macroevolutionary studies assume instantaneous speciation, an unrealistic premise that limits the interpretation of speciation and extinction rates. The protracted birth–death (PBD) model instead assumes that speciation involves two steps: initiation and completion. In order to understand their respective influence on macroevolutionary speciation rates, we compute a standard time-varying BD scenario that is ‘equivalent’ to the PBD model in terms of speciation and extinction probabilities. First, we find a sharp decline in the equivalent birth rate near the present, indicating that rates estimated at the tips of phylogenies may not accurately reflect the underlying speciation process. Second, the completion rate controls the timing of the decay rather than the asymptotic equivalent rates. The equivalent birth rate in the past scales with the speciation initiation rate, with a scaling factor depending mostly on the population extinction rate. Our results suggest that the rates of population formation and extinction may often play a larger role than the speed of accumulation of reproductive isolation in modulating speciation rates. Our study establishes a theoretical framework for understanding how microevolutionary processes combine to explain the diversification of species on macroevolutionary time scales.

This article is part of the theme issue ‘“A mathematical theory of evolution”: phylogenetic models dating back 100 years’.
Genomic insights into an outbreak of SHV-98, TEM-1 and DHA-1 producingKlebsiella pneumoniaein a paediatric cardiac unit
Authors: Fraser Alice J. , Parry Christopher M. , Larru Beatriz , Case Lindsay , Ball Kate , Duggan Caitlin , Edwards Thomas , Heinz Eva
Published: February 2025

This study reports the outbreak of a carbapenem-resistantKlebsiella pneumoniaeclonal lineage in a specialist children’s hospital in Liverpool, UK. Carbapenem resistantK. pneumoniaeis unusual in the UK, and the identification of two cases in the same ward in December 2022 raised concerns and triggered an outbreak investigation. This led to the identification of a potential transmission hotspot in the form of shared equipment, and 11 patients that were colonized or both colonized and infected by a phenotypically similar strain were identified. Multi-locus sequence typing supported a clonal lineage, and whole-genome sequencing was performed on all isolates using short-read sequencing; three isolates were furthermore long-read sequenced to confidently resolve the plasmid structure. Comparing the whole-genome sequences confirmed a clonal lineage and strongly supports the suspected nosocomial transmission, highlighting again the risk ofK. pneumoniaeby its ability to colonise a range of surfaces. Detailed analysis of the resistance determinants indicates that the carbapenem resistance was driven by a combination of different beta-lactamases that would by themselves not convey this resistance profile, a synergistic interaction is thus likely. This highlights how highly resistant strains could be mislabelled as predicted sensitive when considering genetic determinants in isolation, which would have added further complexity to this investigation as the strains would get assessed as a mismatch to the observed resistance profile, and highlights the need to study beta-lactam resistances beyond presence or absence of specific genes but also consider co-occurrence.
Molecular genetic influences on attentional control and other executive processes and their links with psychopathology in the AFFECT study
Authors: Tubbs Justin D. , Mallard Travis T. , Dalby Maria , Jiang Yunxuan , Lee Younga H. , Choi Karmel W. , Ge Tian , Plath Niels , Hammer-Helmich Lene , Granka Julie M. ,   23andMe Research Group, Grotzinger Andrew D. , Hinds David , Smoller Jordan W. , Buckholtz Joshua W.
Published: February 2025

Background

Attentional control is a critical component of executive functioning involved in numerous psychiatric and neurological disorders, yet its etiological relationships with many cognitive and behavioral phenotypes remain underexplored.

Methods

We conducted the first multivariate characterization of molecular genetic influences on attentional control and other executive processes in a cohort of more than 20,000 individuals enriched for mood disorders. We used Genomic Structural Equation Modeling to formally model patterns of genetic covariance among these task-based measures of cognition, as well as their relationships with other cognitive, clinical, and imaging-derived phenotypes.

Results

We identified two independent latent genetic factors: one broadly influencing executive function and one narrowly influencing attentional control. Both theCommon Executive Function (CEF)andAttentional Control (AC)factors were genetically correlated with cognitive and clinical phenotypes, with each latent factor uniquely linked to liability for psychiatric disorders. For example, we observed myriad relationships between the factors and psychopathology, including robust and conditionally independent genetic associations with ADHD. However, despite clear links to brain-related phenotypes, genetic correlations with imaging-derived phenotypes themselves were modest and non-significant after correcting for multiple comparisons.

Conclusions

Overall, the results of our study suggest that genetic influences on attentional control are generally distinct from those that influence broader aspects of executive function. TheCEFandACfactors show distinct patterns of genetic overlap with multiple cognitive and psychiatric outcomes, underscoring the need for more detailed phenotyping of cognition to generate new insights into the etiology of psychopathology.
Structural elucidation of the haptoglobin–hemoglobin clearance mechanism by macrophage scavenger receptor CD163
Authors: Huang Ching-Shin , Wang Hui , White Joshua B. R. , Degtjarik Oksana , Huynh Cindy , Brannstrom Kristoffer , Horn Mark T. , Muench Stephen P. , Somers Will S. , Chaparro-Riggers Javier , Lin Laura , Mosyak Lidia
Published: February 2025

Intravascular hemolysis releases hemoglobin into the bloodstream, which can damage vascular and renal tissues due to its oxidative nature. Circulating haptoglobin acts as a primary defense by binding to free hemoglobin, forming a haptoglobin-hemoglobin (HpHb) complex that is then recognized and cleared by the CD163 scavenger receptor on macrophages. While the function and structure of HpHb complex are mostly well-defined, the molecular mechanism underlying its interaction with CD163 remains unclear. Here we report the cryo-electron microscopy structures of CD163 in its unliganded state and in its complex with HpHb. These structures reveal that CD163 functions as a trimer, forming a composite binding site at its center for one protomer of the dimeric HpHb, resulting in a 3:1 binding stoichiometry. In the unliganded state, CD163 can also form a trimer, but in an autoinhibitory configuration that occludes the ligand binding site. Widespread electrostatic interactions mediated by calcium ions are pivotal in both pre-ligand and ligand-bound receptor assemblies. This calcium-dependent mechanism enables CD163/HpHb complexes to assemble and, once internalized, disassemble into individual components upon reaching the endosome, where low calcium and lower pH conditions prevail. Collectively, this study elucidates the molecular mechanism by which CD163-mediated endocytosis efficiently clears different isoforms of HpHb.
Cooperative mixing through hydrodynamic interactions inStylonychia lemnae
Authors: Turuban Régis , Noselli Giovanni , Beran Alfred , DeSimone Antonio
Published: February 2025

Aquatic microorganisms typically inhabit a heterogeneous resource landscape, composed of localized and transient patches. To effectively exploit these resources, they have evolved a wide range of feeding strategies that combine chemotactic motility with active feeding flows. However, there is a notable lack of experimental studies that examine how these active flows shape resource fields to optimize feeding. In particular, the suspected cooperative hydrodynamics provided by groups of cells remains largely unexplored due to the difficulties in visualizing these dynamic three-dimensional flows. Here, we experimentally investigate howStylonychia lemnaeciliates form feeding clusters of independent cells around food patches. Individual feeding flows interact hydrodynamically to create a chaotic collective flow at the population scale. Using a combination of experimental and numerical techniques, we measure and predict the entire collective flow, enabling us to assess its outstanding mixing and dispersion properties. We show that the active spreading of the food patch accelerates its detection by starving cells. As many additional fitness advantages provided by collective flows can be envisioned, we propose that this feeding cluster represents a form of intra-specific by-product cooperative behavior.
Mediator-29 LimitsCaenorhabditis elegansFecundity
Authors: Fan Qi , Tran Christopher , Cao Wei , Pocock Roger
Published: February 2025

Mediator is an evolutionarily conserved multiprotein complex that acts as a critical coregulator of RNA polymerase II-mediated transcription. While core Mediator components are broadly required for transcription, others govern specific regulatory modules and signalling pathways. Here, we investigated the function of MDT-29/MED29 in theCaenorhabditis elegansgerm line. We found that endogenously-tagged MDT-29 is ubiquitously expressed and concentrated in discrete foci within germ cell nuclei. Functionally, depleting MDT-29 in the germ line during larval development boosted fecundity. We determined that the increase in progeny production was likely caused by a combination of an expanded germline stem cell pool and decreased germ cell apoptosis. Thus, MDT-29 may act to optimize specific gene expression programs to control distinct germ cell behaviors, providing flexibility to progeny production in certain environments.
An image-based biophysical model of the lung to investigate the effect of pulmonary surfactant on lung function
Authors: Neelakantan Sunder , Myers Kyle J. , Rizi Rahim , Smith Bradford J. , Avazmohammadi Reza
Published: February 2025

Lung biomechanics aims to understand the structure-function relationship in the lung under normal and pathological conditions. Pulmonary surfactant has a key structural role in lung function with a significant contribution to the mechanical response of the lungs during respiration. Pulmonary surfactant dynamically regulates surface tension at the air-liquid interface to decrease stiffness during respiration and prevent alveolar collapse during lower volumes. Many lung injuries involve alterations to the contribution of surfactants to lung function. We developed a novel biophysical model using a poroelastic formulation that incorporates pulmonary surfactant dynamics and aims to quantify the contribution of the pulmonary surfactant toward lung compliance. The effect of pulmonary surfactant was modeled as a surface energy function, and the surface behavior was converted to bulk behavior by assuming uniform spherical alveoli. The model was used to simulate respiration and investigate the effect of altered surface tension caused by surfactant dysfunction. The model captured the characteristic sigmoidal inspiratory pressure-volume curve and hysteresis observed during clinical measurements. In addition, the model predicted the expected behavior in surfactant dysfunction in lung injuries. We expect this work to serve as an essential step towards de-convoluting and predicting the contributions of the lung parenchyma and pulmonary surfactant to global and regional lung compliance in health and disease.
Immunological surveillance using gSG6-P1 biomarker reveals spatio-temporal dynamics ofAnophelesexposure and gaps in malaria risk assessment
Authors: Saeung Manop , Jupatanakul Natapong , Jampeesri Niramon , Afelt Aneta , Chareonviriyaphap Theeraphap , Manguin Sylvie
Published: February 2025

Malaria risk assessment often relies on the entomological inoculation rate (EIR), which quantifies infectious bites per person over time. However, this approach does not account for human behavioral variability, limiting its effectiveness in accurately reflecting malaria risk at the population level. Recent studies have attempted to estimate mosquito-bite risk through the measurement of antibody responses toAnophelessalivary peptides. However, this approach has yet to be applied to evaluate malaria transmission risks along the Thailand-Cambodia border. This study aims to employ an immune biomarker forAnophelessalivary peptide (anti-gSG6-P1) to identify key risk factors associated with exposure toAnophelesmosquitoes in Sisaket Province, a region bordering Thailand and Cambodia. Blood samples from the same set of 184 participants were collected via finger prick during each season: rainy (August 2022), cool-dry (December 2022), and hot-dry (April 2023). Anti-gSG6-P1 antibody levels were quantified using enzyme-linked immunosorbent assay (ELISA). Factor Analysis of Mixed Data (FAMD) revealed that seasonality exerts the strongest influence on antibody levels. This pattern was likely driven by human activities, particularly the frequency of rubber tapping activity in the rubber plantation area whereAnophelesspecies, especiallyAnopheles dirus,are present. While this study successfully identifies seasonality and human factors as critical influences on antibody responses, it also highlights gaps in understanding the kinetics of anti-salivary peptide responses toAnophelesbites, particularly in species with low salivary peptides sequence similarity to that ofAnopheles gambiae. These findings emphasize the need for the development of new serological tools tailored to malaria vectors in the Greater Mekong Subregion to enhance malaria risk assessment and improve vector control strategies.
Automated IntraVascular UltraSound Image Processing and Quantification of Coronary Artery Anomalies: The AIVUS-CAA software
Authors: Stark Anselm W. , Mohammadi Kazaj Pooya , Balzer Sebastian , Ilic Marc , Bergamin Manuel , Kakizaki Ryota , Giannopoulos Andreas , Haeberlin Andreas , Räber Lorenz , Shiri Isaac , Gräni Christoph
Published: February 2025

Background

Coronary artery anomalies (CAA) with an intramural course are associated with elevated risks of ischemia and sudden cardiac death under stress. Intravascular ultrasound (IVUS) is essential for assessing coronary vessel dynamics in these patients. However, the rarity of such anomalies, along with unique geometric changes in the intramural course and ostium, complicates image analysis, leading to inconsistencies and time-consuming evaluations. Our developed executable, zero/low-code software addresses these limitations by providing automated lumen segmentation and cardiac phase identification in IVUS images acquired during rest and stress protocols.

Methods

The software includes: (1) Automated segmentation of lumen contours trained and validated on 6713 frames (developed by using human in the loop active learning process) and tested on 914 frames, IVUS frames from fifteen patients (22 studies) with right CAA using a modified U2-Net deep learning (DL) model; (2) Extraction of systolic and diastolic frames via a dual-gating approach combining image- and contour-based methods; and (3) A graphical user interface enabling manual correction of the results. The gating module was validated using a custom flow-loop simulating patient-specific hemodynamics, while segmentation accuracy was assessed via intra-class correlation coefficient (ICC) analysis comparing AI-generated contours with those delineated by experienced readers.

Results

The DL model achieved a mean Dice score of 0.86 (SD: 0.07), sensitivity of 0.87 (SD: 0.11), and specificity of 0.98 (SD: 0.01) on the test set. ICC values for lumen area measurements were 0.92 (95%CI: 0.88-0.95) for rest and 0.98 (95%CI: 0.97-0.99) for stress conditions (allp <0.001). The gating module demonstrated excellent reproducibility for identifying systolic and diastolic frames under both conditions (ICC = 1.00,p <0.001).

Conclusions

AIVUS-CAA offers a reliable, automated tool for precise IVUS analysis at rest and during stress, enhancing the evaluation of geometrical changes of coronary vessels in CAA patients and enabling efficient clinical decision-making in a streamlined workflow.Graphical Abstract

Highlights

Developed the first automated software (AIVUS-CAA) specifically designed to quantify dynamic geometric changes in coronary artery anomalies, addressing a critical gap in analyzing intramural coronary segments.

Introduced a novel dual-gating algorithm combining image-based and contour-derived signals to identify systolic/diastolic phases, validated under both rest and simulated exercise conditions – a first for stress IVUS analysis in CAA.
Year-round rhythms: alpine plant species modulate soil and microbial dynamics during the growing season and under the snow
Authors: Ruka Adam Taylor , Schweichhart Johannes , Dolezal Jiri , Čapková Kateřina , Chlumská Zuzana , Calvillo-Medina Rosa Paulina , Meador Travis B. , Praeg Nadine , Illmer Paul , Angel Roey , Rehakova Klara
Published: February 2025

Soil-plant-microbe interactions are integral throughout most terrestrial ecosystems, yet the importance of plant phenology and seasonal dynamism upon these relationships remains unknown. Given the pronounced seasonality of alpine environments, we sampled 8 plant species occurring in two habitats (alpine meadow and subnival zone) across four seasons (including snow-covered winter) in the Central Eastern Alps to determine the plant growth strategies and plant nutrient parameters which closely couple with rhizosphere microbial parameters.

In subnival locations, plants exhibited stronger seasonal changes among leaf and root tissue nutrient concentrations and non-structural carbohydrates (NSCs) compared to those in lower elevation alpine meadows. However, rhizosphere microbial parameters (microbial biomass (MBC), extracellular enzymes, and community composition) demonstrated more seasonal changes in the alpine meadow locations.

A phenological delay was observed in bacterial and fungal communities of the subnival zone, with peak plant rhizosphere differentiation occurring later in the season than in alpine meadows. Therefore, the prolonged cold conditions and shorter growing season in higher elevations likely add a temporal aspect to the commonly used elevational gradient approach, which is not often considered.

MBC and enzymatic potential within the rhizosphere were high across all plant species in the alpine meadow during the winter sampling, despite notable differences in microbial community composition. In contrast, winter rhizosphere communities did not differ between plant species in subnival locations, although one species,Oxyria digyna, demonstrated much higher microbial activity along with higher NSCs and root N, suggesting some alpine plant species may acquire nutrients through microbial interactions during snow-covered winter periods.

Synthesis: This study provides the first look at the annual phenology of multiple alpine plant species and their associated rhizosphere microbiome. Our results demonstrate that seasonal microbial dynamics are highly influenced by abiotic factors (soil and microclimatic conditions), but plants are able to modulate these conditions through growth and nutrient acquisition strategies. Taken together, seasonality and independent plant species effects cannot be overlooked when assessing habitat nutrient cycling and ecosystem stability.
Two new yeast species of the genusVishniacozymaisolated from the phylloplane ofEquisetum sylvaticum
Authors: Golubev Wladyslav
Published: February 2025

Five yeast strains belonging to the genusVishniacozymaLiu et al. were isolated from horsetail in Moscow region (Russia). By morphological and physiological properties, they are similar to the speciesV. carnescens, V. peneausandV. victoriaebut differ in mycocin-sensitivity profiles. These isolates represent two novel species, for which the namesV. equsetis(type strain VKM Y-2979) andV. paraequisetis(type strain VKM Y-2980) are proposed.