bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the number of primary versus incidental COVID-19 hospitalizations in Santa Clara County
Authors: Smith Rosamond , D’Agostino Alexis , Stoddard Pamela , Kamal Ahmad , Kelsey Kate , Li Linlin , Lin Wen , Enanoria Wayne T A , Rudman Sarah L , Hoover Christopher
Published: February 2025

Background

The goal of this study is to evaluate whether ICD-10 discharge data can be used to accurately differentiate primary COVID-19 hospitalizations, which are specifically due to COVID-19, from incidental COVID-19 hospitalizations for monitoring COVID-19 trends in one large county health department. We sought to explore the use of machine learning algorithms for enhancing surveillance capabilities in a local public health setting.

Methods

Discharge data for 5,122 Santa Clara County hospitalizations with a positive SARS-CoV-2 PCR or antigen test occurring between December 15, 2021 and August 15, 2022 were used to train a series of models for classifying primary COVID-19 hospitalizations, using chart review as a gold standard. Area under the receiver operator characteristic curve (AUROC) was used as the evaluation metric.

Results

Each model performed well when trained on the full set of available predictors. AUROC values ranged from 0.808 (random forest) to 0.818 (SuperLearner). After evaluating each model, we implemented a reporting process based on the LASSO (Least Absolute Shrinkage and Selection Operator) logistic regression, as the performance was comparable with the SuperLearner and it had the advantage of being transparent and familiar to health department staff.

Conclusions

In Santa Clara County, ICD-10 discharge data was successfully used to develop a low burden method for monitoring primary COVID-19 hospitalization, demonstrating one way that predictive algorithms can help local health jurisdictions meet surveillance needs while minimizing manual effort.
The Movement System and Diagnosis: Are we There Yet?
Authors: McClure Philip
Published: February 2025

In the 29th Maley lecture, Phil McClure PT, PhD, FAPTA, shares a Perspective regarding the movement system and diagnosis. Despite declarations from the House of Delegates over 10 years ago, the concept of a movement system has not been widely embraced in either education or practice. In this perspective, he offers critical analysis and 3 proposals that could potentially make the concept of a movement system more relevant and meaningful. The first is to operationally define the movement system, arguing that the current definition is too vague and not operational, and therefore not meaningful. The second is to intentionally separate the movement system from any specific diagnostic classification scheme which would allow the focus to remain on movement and movement analysis. He argues that diagnostic classification schemes require a biopsychosocial framework and that movement, while important, cannot be the only consideration. The third proposal is that diagnostic schemes must be developed by clinical scientists through appropriate research guided by sound theory, not by administrative or political process. He further argues that a greater focus on determining which patients are likely to be helped by physical therapists is necessary and offered the example of developing “appropriateness criteria” as a tool towards promoting value-based care. Achieving broad consensus around these proposals could unify our professional focus and assist toward the vision of optimizing movement to enhance the human experience.
Microenvironmental dynamics in steady-state and stress erythropoiesis
Authors: Yang Chong , Suda Toshio
Published: February 2025

Anemia is a condition marked by a shortage of red blood cells or hemoglobin, resulting in a diminished ability of the blood to carry oxygen. In response to anemia or hypoxia, the body activates a compensatory mechanism known as stress erythropoiesis. This crucial physiological process results in increased erythrocyte production, particularly in extramedullary sites such as the spleen and liver, to restore adequate oxygen levels. Unlike steady-state erythropoiesis, which primarily occurs in the bone marrow, stress erythropoiesis depends on distinct progenitor cells and signaling pathways within a specialized erythroid niche in adult spleen and liver. This niche provides essential support for the proliferation, differentiation, and maturation of erythroid progenitors during anemic stress. The dynamics within this niche under stress conditions involve complex interactions between progenitor and niche cells. These interactions are regulated by specific molecular signals that adapt to the body’s physiological demands, ensuring an appropriate response to stress. This review explores the cellular and molecular mechanisms governing these processes, highlighting the extrinsic pathways and cellular interactions during stress erythropoiesis. In addition, it underscores the need for future research to translate findings from murine models into therapeutic strategies for treating anemia-related diseases.
Cancer Incidence and Mortality in Familial Adenomatous Polyposis Syndrome
Authors: Feldman Dan , Rodgers-Fouche Linda H. , Ukaegbu Chinedu , Yurgelun Matthew B. , Syngal Sapna , Chung Daniel C.
Published: February 2025

BACKGROUND:

Risk-reducing colectomy in familial adenomatous polyposis syndrome is the standard of care. This has increased the importance of surveillance for extra-colonic malignancies in post-colectomy individuals.

OBJECTIVE:

We sought to define the present-day incidence of all cancers and mortality in familial adenomatous polyposis.

DESIGN:

Retrospective longitudinal cohort study.

SETTINGS:

Two large academic hospitals.

PATIENTS:

Eligible patients carried an APC pathogenic variant or met clinical criteria for familial adenomatous polyposis.

MAIN OUTCOMES MEASURES:

Cancer diagnosis, mortality, associated risk factors.

RESULTS:

A total of 358 patients were identified. The percentage who exhibited a classic familial adenomatous polyposis phenotype was 63.7%; 21.2% were de novo, and 82.7% had a colectomy. Colorectal cancer was the most common cancer (N = 59, 16.5%). Colorectal cancer diagnoses were associated with de novo familial adenomatous polyposis (odds ratio 7.8 [95% CI 3.51-17.35; p < 0.001]). Thyroid, duodenal/small bowel, gastric, and neuroendocrine tumors were reported in 7.5%, 3.1%, 2.8%, and 2.5% of patients, respectively. Rates of cancer were similar in classic and attenuated familial adenomatous polyposis. Thirty-nine patients (10.9%) died at a mean age of 49.6±17.1 years. Twenty-six deaths were malignancy-related, and colorectal cancer was the leading cause (N = 10). All colorectal cancer-related deaths occurred in individuals with classic familial adenomatous polyposis, and 9/10 were not previously diagnosed with the syndrome. Gastric and duodenal/small bowel cancer were the second leading causes (4 deaths each), and all occurred after colectomy. Fifty-nine percent of all deaths were attributable to a familial adenomatous polyposis-related malignancy or morbidity.

LIMITATIONS:

Retrospective clinical data.

CONCLUSIONS:

Colorectal cancer remains the most common malignancy and cause of death in familial adenomatous polyposis. However, nearly all colorectal cancer-related deaths occurred in individuals unaware of their familial adenomatous polyposis diagnosis, and none occurred in the attenuated syndrome. In patients who had a colectomy, gastric and duodenal/small bowel cancers are now the leading causes of death. See Video Abstract.
Effect of Low-Load Blood Flow Restriction Training and High-Load Resistance Training on Quadriceps Strength, Dynamic Stability, and Functional Performance
Authors: Adhitya I Putu Gde Surya , Aryana I Gusti Ngurah Wien , Kurniawati Ida , Thanaya Sayu Aryantari Putri , Utama Made Bang Redy
Published: February 2025

Objective:

Blood flow restriction (BFR) is a method used to affix a pneumatic cuff to the uppermost part of a leg. Blood flow restriction is often combined with low load-blood flow restriction training (LL-BFRt) to enhance strength and promote muscle hypertrophy. Therefore, this research aimed to examine the effect of LL-BFRt, sham LL-BFRt, and high load-resistance training (HL-Rt) on quadriceps strength (QS), dynamic stability, and functional performance.

Design:

Single-blinded randomized trial method.

Setting:

A private physical therapy clinic in Bali, Indonesia.

Participants:

Data were collected from 63 basketball and rugby players assigned to 3 intervention groups, namely, LL-BFRt, sham LL-BFRt, and HL-Rt, through block randomization.

Independent Variables:

Each participant received intervention consisting of 45-minute sessions twice per week for 8 weeks.

Outcome Measures:

Quadriceps strength, star excursion balance test (SEBT), and single-leg hop test (SLHT) were evaluated in baseline, 4 weeks, and 8 weeks of the intervention period.

Results:

In LL-BFRt and HL-Rt groups, QS, SEBT, and SLHT scores were significantly improved during 8-week intervention period, except in sham LL-BFRt group. Furthermore, there was a significant improvement in LL-BFRt (

QS: 9.2-33.5 Newton;

SEBT: 1.2-11.1 cm;

SLHT: 1.3-9.8 cm, P-values < 0.05) and HL-Rt groups (

QS: 15.4-35.9 Newton;

SEBT: 2.2-9.0 cm;

SLHT: 4.5-15.8 cm, P < 0.05) compared with sham LL-BFRt.

Conclusions:

The improvements attained by participants using LL-BFRt and HL-Rt were comparable and capable of improving QS, SEBT, and SLHT more than sham LL-BFRt.

Trial Registration:

NCT05951036.
Self-advocacy Among Women With Uterine Malignancies
Authors: Chen Xiaojie , Xu Xiaohan , Du Yunhong , Liu Wei , Zhang Xiao , Wang Li
Published: February 2025

Background:
Self-advocacy plays a crucial role in the mental health and treatment outcomes of oncology patients, particularly those with uterine malignancies. Despite its significance, research on the self-advocacy levels and influencing factors among Chinese patients with uterine malignancies remains limited.

Objectives:
To assess the self-advocacy levels among Chinese patients with uterine malignancies and identify the demographic, psychological resilience, and decision self-efficacy factors that influence self-advocacy.

Methods:
This cross-sectional study was conducted from March 1 to September 1, 2023, involving 220 inpatients with uterine malignancies from three tertiary hospitals in Shandong Province, China. Participants were recruited using convenience sampling and completed the General Information Questionnaire, Female Cancer Survivorship Self-advocacy Scale, Connor–Davidson Resilience Scale, and Decision Self-efficacy Scale.

Results:
The average self-advocacy score among participants was 59.44 ± 10.14. Significant positive correlations were found between self-advocacy, psychological resilience, and decision self-efficacy. The random forest algorithm identified decision self-efficacy, psychological resilience, family average income, type of medical insurance, educational level, and residence as the six most important influencing factors, with the optimal model performance observed when lambda (λ) = 1.191. Multiple linear regression analysis further confirmed that decision self-efficacy, psychologic resilience, family average income, educational level, and residence were significant predictors of self-advocacy.

Discussion:
The self-advocacy levels of Chinese patients with uterine malignancies were relatively low, with decision self-efficacy, psychological resilience, and socioeconomic factors significantly influencing their self-advocacy abilities. Future targeted interventions should focus on enhancing patients’ decision self-efficacy and psychological resilience, thereby guiding them to actively respond and participate in decision-making, ultimately improving self-advocacy among patients with uterine malignancies.
Budget Impact of Eliminating Medicaid Prior Authorizations for Antiretrovirals in Washington State
Authors: Golden Matthew R. , Taketomo Ryan T. , Pistoresi Ryan , Sullivan Donna
Published: February 2025

Background

In 2023, Washington state Medicaid eliminated prior authorizations (PAs) for antiretrovirals (ARVs). We estimated the budget impact of this policy change on Medicaid ARV expenditures, 2023-2027.

Methods

Models used 2022 net drug costs reflecting costs minus rebates. Our base case pre-exposure prophylaxis (PrEP) model assumed changes in the proportions of PrEP users on tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), tenofovir alafenamide/emtricitabine (TAF/FTC), and cabotegravir (CAB) based on 2021-2022 data (prior to elimination of PAs). We compared base case costs to models assuming changes in PrEP prescribing observed 2022-2023 (first year after elimination of PAs), and models assuming an accelerated increase in TAF/FTC and CAB use. For HIV treatment, models assumed ARV changes based on 2021-2022 data (Base Model), changes based on data from 2022-2023 (No PA – Stable Increase), and a model based on 2022-2023 data but with a declining rate of change in the adoption of bictegravir/TAF/FTC and CAB/rilpivirine (No PA – Declining Increase). We estimated the number of persons with HIV (PWH) who might be housed using money required to meet new ARV costs using 2023 local Ryan White Program costs for emergency or temporary housing.

Results

Elimination of PAs will increase Medicaid expenditures for ARVs by an estimated $109.9-$157.7 million over 5 years. This cost would pay for 5 years of housing for approximately 820-1,177 people, or 61-88% of unstably housed PWH in Washington state.

Conclusions

Elimination of Medicaid PAs will result in substantial new costs. Changes in drug formulary policy should consider opportunity costs.
Systematic Review and Meta-Analysis of Prevalence and Population-Level Factors Contributing to Posttraumatic Stress Disorder in Pediatric Intensive Care Survivors
Authors: Hay Rebecca E. , O’Hearn Katie , Zorko David J. , Lee Laurie A. , Mooney Sarah , McQuaid Cara , Albrecht Lisa , Henshall David E. , Dannenberg Vanessa Campes , Flamenghi Veronica , Thibault Celine , Lee Wai Kit , Shi Min Ko Michelle , Cree Michele , St. Louis Julia , Heneghan Julia A. , Leung Karen Ka Yan , Wood Andrea , López-Barón Eliana , Temsah Mohamad-Hani , Almazyad Mohammed , Retallack Jennifer , Reddy Mounika , Aldairi Nedaa , Palomino Rubén Eduardo Lasso , Choong Karen , Du Pont-Thibodeau Geneviève , Ducharme-Crevier Laurence , Tsampalieros Anne , Hayawi Lamia , McNally James Dayre M. , Garcia Guerra Gonzalo
Published: February 2025

Objectives:

In survivors of illnesses or surgeries requiring PICU admission, there is a risk of posttraumatic stress disorder (PTSD). We aimed to estimate PTSD prevalence and potential contributing factors in survivors of PICU admission.

Data Sources:

We performed a PROSPERO registered systematic review (CRD42022348997; Registered August 2022) using MEDLINE, Embase, CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL) databases, 2000 to 2022, with no language restrictions.

Study Selection:

Observational or interventional studies evaluating the incidence or prevalence of PTSD in patients’ after PICU admission and/or contributing factors to PTSD. We used studies describing patients younger than 18 years old. Since there were a large number of citations, we used an integrated crowdsourcing and machine-learning model for citation screening. Each citation was reviewed independently and in duplicate by two reviewers at each stage of screening and abstraction.

Data Extraction:

Data items included study and participant demographics, details of case definition (PTSD screening), and risk factors.

Data Synthesis:

We followed the Preferred Reporting items for Systematic Reviews and Meta-analysis guidelines. Random-effects models were used to analyze PTSD prevalence and subgroup differences. In 24 citations meeting final review criteria, 19 had data for meta-analysis. There were 1898 PICU survivors with a median (interquartile range) cohort size of 59 (49–76). PTSD prevalence in the studies ranged from 3% to 37%; PTSD occurred in 529 of 1898 survivors (I
2 = 72%). Factors influencing PTSD variability included timing of assessment (p < 0.01) with the highest prevalence (29%) at 6 months and the type of assessment instrument (n = 10; range, 4–27%; p = 0.04). There was lower prevalence of PTSD (8%) in postoperative cardiac patients (p < 0.01). Last, we failed to find an association between PICU length of stay and PTSD prevalence (p = 0.62; I
2 = 80%).

Conclusions:

PICU follow-up studies from 2000 to 2022 indicate that one-in-three of admissions surviving to 6 months have PTSD. However, there are population, study design factors and heterogeneity in PTSD assessment that indicate more standardization in this research is needed.
Temporary Femoral Central Venous Catheters in the PICU: Two-Center, Retrospective Cohort Study of Catheter Tip Position and Symptomatic Venous Thromboembolism, 2016–2021
Authors: Good Ryan J. , Ahern Emily , Weber Mark D. , Miller Kristen R. , DeVine Mackenzie , Mehta Sanjiv D. , Conlon Thomas W. , Himebauch Adam S.
Published: February 2025

Objectives:

We aimed to determine the frequency and variables associated with low femoral central venous catheter (fCVC) tip position. We also examined the association between tip position and symptomatic venous thromboembolism (VTE).

Design:

Retrospective cohort from two PICUs.

Setting:

Quaternary academic children’s hospitals, 2016–2021.

Patients:

Children (age <18 yr) in the PICU who underwent temporary fCVC placement.

Interventions:

None.

Measurements and Main Results:

Low fCVC tip position occurs when the tip is inferior to the fifth lumbar vertebra (L5) on a postprocedural abdominal radiograph. Of 936 patients: 56.3% were 1–12 years old, and 80.0% had normal weight-for-age z score. fCVC tip position was low in 67.3% of patients. In the multivariable model, older age, earlier years of placement, and higher weight-for-age were associated with low fCVC tip position. Symptomatic fCVC-associated VTE occurred in 8.8% of patients, with a rate of 16.5 per 1000 CVC days (interquartile range, 13.1–20.5 per 1000 CVC days). The percentage of VTE in low vs. recommended fCVC tip position and VTE (8.6% vs. 9.2%) were equivalent (two one-sided z-tests; p < 0.001). Furthermore, in the multivariable model, we failed to identify an association between low fCVC tip position, relative to the recommended tip position, and greater odds of VTE (OR, 1.58 [95% CI, 0.92–2.69). However, we cannot exclude the possibility of low fCVC tip position being associated with up to 2.6-fold greater odds of symptomatic VTE.

Conclusions:

In our two PICUs, 2016–2021, low fCVC tip position occurred in two-thirds of placements and was associated with older age and higher weight-for-age patients. fCVC-associated VTE occurred in one-in-11-catheter placements, with the raw percentage of fCVCs and subsequent VTE in low and recommended tip position being equivalent. However, the multivariable modeling indicates that future research into the relationship between tip position and VTE requires ongoing surveillance and work.
Evolving Epidemiology of Increasing Trauma Deaths in the UNITED STATES (2000-2020)
Authors: Rhee Peter , Holcomb John B. , Zangbar Bardiya
Published: February 2025

Background:

Over the past two decades, the epidemiology of trauma has shifted significantly, driven primarily by demographic changes. Aim of our study was to illustrate the changing landscape of trauma mortality rates and compare them with other leading causes of death.

Methods:

We performed a cross-sectional study from 2000-2020, using data from the CDC and WISQARS™. Trauma deaths were defined according to the WHO classification, encompassing unintentional injuries, homicides, and suicides. Mortality rates were calculated per 100,000 using US census data.

Results:

The analysis revealed a 91% increase in trauma mortality from 2000-2020, rising to 268,926 deaths—far surpassing the 17.8%population growth. A trimodal distribution of trauma deaths persisted, with age peaks shifting to 30-35,55-59, and above 70 years by 2020. Causes of death shifted with increases in firearm, poisoning, and fall, while motor vehicle mortality rates declined. By 2020, trauma was the leading cause of death up to age 50. Trauma remained the leading cause of cumulative deaths up to age 67 and the primary contributor to years of life lost. Death rates from cancer and heart disease showed a declining trend.

Conclusions:

Trauma has become the leading cause of death up to age 50 and remains a primary contributor to years of life lost. The largest increase in trauma deaths was noted among baby boomers and millennials. As death rates from cancer and heart disease decline, it is essential to reprioritize and reallocate resources to address the evolving trauma epidemiology in an aging and expanding U.S. population.

Level of Evidence:

Level III retrospective study
Comparison of Timing of Definitive Pelvic Fixation in Pelvic Fracture Treated with Preperitoneal Pelvic Packing or Angioembolization
Authors: Kwon Junsik , Allison-Aipa Timothy , Zakhary Bishoy , Coimbra Bruno C , Firek Matthew , Coimbra Raul
Published: February 2025

Background:

Preperitoneal pelvic packing (PPP) and angioembolization (AE) are current hemostatic techniques in bleeding pelvic fracture patients. Concerns exist that PPP may delay definitive internal fixation of pelvic fractures. This study aims to determine whether PPP results in delayed internal fixation compared to AE.

Study Design:

A retrospective cohort study was conducted using the Trauma Quality Improvement Program database from 2017 to 2021. Adults with isolated pelvic fractures requiring transfusion within 24 hours were included. Patients underwent internal fixation and received either PPP (n=90) or AE only (n=253). Inverse probability of treatment weighting was used to adjust for confounding variables. The primary outcome was time from admission to internal fixation; secondary outcomes included in-hospital mortality and hospital resource utilization.

Results:

Time to definitive fixation was not significantly different between groups (PPP median 51.4 hours vs. AE median 37.5 hours; p=0.071). In-hospital mortality was higher in the PPP group (4.4% vs. 0.6%; p=0.009). The PPP group had longer ICU and hospital stays, extended mechanical ventilation duration, and higher rates of acute kidney injury and severe sepsis. No significant difference in transfusion volume within 4 hours was observed between the groups.

Conclusions:

PPP does not significantly delay definitive internal fixation. However, the implementation of PPP for patients with pelvic fractures may be associated with increased complications and hospital resource utilization compared to AE alone as a hemostatic measure.
Opportunities for Microbiology Citizen Science: Lessons Learnt from Three Pilot Projects
Authors: Pateman Rachel M , Bennett Joyce , Hilton Anthony C , Romeo-Melody Isabella , Rosenfeld Anton , Routledge Sarah J , Rymer Caroline , Swift Benjamin MC , Way Lucy , Whatford Louise , Wilkinson Naomi C , Worthington Tony , Yandle Lewis , Younis Ayesha S , West Sarah E , Goddard Alan D
Published: February 2025

Citizen science is the partnering of professional scientists and members of the public to answer real world scientific questions. There has been huge growth in citizen science over the past two decades but uptake in microbiology research has, thus far, been relatively limited. In the first part of this paper we discuss how citizen science is well aligned with microbiology research: sample collection methods can be simplified and used in a variety of environments; projects are expected to appeal to participants as topics are likely to be of relevance to people’s lives and interests, including the health of people and the environment; and projects can also lead to real world impact, including the identification of new drugs or biotechnological solutions. In the second part of the paper, we present our reflections from three pilot projects we have recently completed. In order for the field to grow, people need to share both their successes as well as the challenges they have faced, so others wanting to use the method can learn from these experiences. We share simplified sampling methods for yeast strains from home brewing and baking, antimicrobial resistant bacteria on home grown produce and microbes on chopping boards. However, participation in our projects was limited by a range of factors, including time available and resourcing, which impacted on our ability to generate new knowledge and wider impacts. We provide recommendations for others wishing to run microbiology citizen science projects, including ensuring appropriate resourcing and considering ethical implications of projects.
In vitro activity of cefiderocol against Pseudomonas aeruginosa isolated from adult patients with cystic fibrosis
Authors: Ali Saied , McDermott Sinead
Published: February 2025

Background
Pseudomonas aeruginosa is an opportunistic pathogen that commonly infects the cystic fibrosis (CF) lung, promoting a rapid decline in pulmonary function. It exhibits significant resistance to innate immune effectors and antimicrobials by expressing specific virulence factors and by acquiring adaptive mutations during chronic infection, often proving challenging when devising effective treatment regimens. Cefiderocol (FDC) is a novel siderophore cephalosporin with activity against Gram-negative pathogens. We aimed to assess the in vitro efficacy of cefiderocol against P. aeruginosa isolates in a CF population.
Methods
The study was conducted in a tertiary hospital with a specialist adult CF service caring for approximately 300 patients. All first isolates of significant respiratory pathogens among this cohort are cryopreserved at -80°C. Antimicrobial susceptibility testing to FDC was performed as per EUCAST Disk-Diffusion (Version 10) for all stored isolates of P. aeruginosa from 2017-2022 inclusive.   
Results
Eighty-five isolates from seventy-one patients were examined during the study period. The average age of patients was 30 years, with the average age at which P. aeruginosa was first isolated being 24 years (IQR 18-28) and the average age of isolation of a mucoid phenotype being 32 years (IQR 25-38). Forty-one percent (n=35) of isolates were classified as non-multidrug-resistant, 19% (n=16) multidrug-resistant, 16% (n=14) extensively drug-resistant and 24% (n=20) pandrug-resistant; with 24% (n=20) exhibiting the mucoid phenotype. With a zone of ≥22 mm indicating susceptibility to FDC, only 13 isolates (15%) were deemed non-susceptible, with an overall average disk-diffusion zone of 25.2 mm.  
Conclusion
Cefiderocol exhibited excellent in vitro anti-pseudomonal activity against isolates obtained from an adult CF population.
Predicting the bacterial host range of plasmid genomes using the language model-based one-class support vector machine algorithm
Authors: Feng Tao , Chen Xirao , Wu Shufang , Tang Waijiao , Zhou Hongwei , Fang Zhencheng
Published: February 2025

The prediction of the plasmid host range is crucial for investigating the dissemination of plasmids and the transfer of resistance and virulence genes mediated by plasmids. Several machine learning-based tools have been developed to predict plasmid host ranges. These tools have been trained and tested based on the bacterial host records of plasmids in related databases. Typically, a plasmid genome in databases such as the National Center for Biotechnology Information is annotated with only one or a few bacterial hosts, which does not encompass all possible hosts. Consequently, existing methods may significantly underestimate the host ranges of mobile plasmids. In this work, we propose a novel method named HRPredict, which employs a word vector model to digitally represent the encoded proteins on plasmid genomes. Since it is difficult to confirm which host a particular plasmid definitely cannot enter, we developed a machine learning approach for predicting whether a plasmid can enter a specific bacterium as a no-negative samples learning task. Using multiple one-class support vector machine (SVM) models that do not require negative samples for training, HRPredict predicts the host range of plasmids across 45 families, 56 genera and 56 species. In the benchmark test set, we constructed reliable negative samples for each host taxonomic unit via two indirect methods, and we found that the area under the curve (AUC), F1-score, recall, precision and accuracy of most taxonomic unit prediction models exceeded 0.9. Among the 13 broad-host-range plasmid types, HRPredict demonstrated greater coverage than HOTSPOT and PlasmidHostFinder, thus successfully predicting the majority of hosts previously reported. Through feature importance calculation for each SVM model, we found that genes closely related to the plasmid host range are involved in functions such as bacterial adaptability, pathogenicity and survival. These findings provide significant insight into the mechanisms through which bacteria adjust to diverse environments through plasmids. The HRPredict algorithm is expected to facilitate in-depth research on the spread of broad-host-range plasmids and enable host-range predictions for novel plasmids reconstructed from microbiome sequencing data.
DEEP LEARNING-BASED PHENOTYPING OF FOREFOOT MORPHOLOGY IN HEREDITARY THORACIC AORTIC DISEASES
Authors: Pizzagalli Diego Ulisse , Grego Susanna , Demertzis Stefanos
Published: February 2025

Hereditary thoracic aortic diseases (HTAD) are often associated with multifaceted phenotypic manifestations in different anatomical districts, including skeletal abnormalities. Therefore, diagnostic criteria account for multiple parameters to compute a systemic risk score. Despite the forefoot is known to be different in HTAD, its complex morphology is difficult to be quantified objectively and it is not currently considered in diagnostic criteria.

Here, we investigated the potential application of artificial intelligence to compute a HTAD risk score from smartphone-acquired images of the forefoot. To this end, we conducted a pilot study including 44 adults, of which 22 had high risk of HTAD (in line with EACTS/STS guidelines 2024 and revised Ghent criteria). The remaining 22 individuals did not show characteristic features indicative of HTAD. A deep learning architecture was then trained to compute a risk score using specific strategies to account for limited sample sizes: transfer learning and leave-one-out cross validation.

The computed risk score was significantly higher in the HTAD group with respect to the control group (p < 0.0001), achieving remarkable sensitivity (82%) and specificity (91%), with an AuC of 0.94.

Altogether this study highlights the usefulness of AI to assist the analysis of complex morphological traits, potentially enabling a greater number of healthcare professionals to identify patients at risk of HTAD and readily address them to a proper clinical examination.

The study was approved by the Swiss Cantonal Ethics Committee with protocol number 2023-00643.
Long-read sequencing resolves the clinically relevantCYP21A2locus, supporting a new clinical test for Congenital Adrenal Hyperplasia
Authors: Monlong Jean , Chen Xiao , Barseghyan Hayk , Rowell William J , Negi Shloka , Nokoff Natalie , Mohnach Lauren , Hirsch Josephine , Finlayson Courtney , Keegan Catherine E. , Almalvez Miguel , Berger Seth I. , de Dios Ivan , McNulty Brandy , Robertson Alex , Miga Karen H. , Speiser Phyllis W. , Paten Benedict , Vilain Eric , Délot Emmanuèle C.
Published: February 2025

Congenital Adrenal Hyperplasia (CAH), one of the most common inherited disorders, is caused by defects in adrenal steroidogenesis. It is potentially lethal if untreated and is associated with multiple comorbidities, including fertility issues, obesity, insulin resistance, and dyslipidemia. CAH can result from variants in multiple genes, but the most frequent cause is deletions and conversions in the segmentally duplicated RCCX module, which contains theCYP21A2gene and a pseudogene.

The molecular genetic test to identify pathogenic alleles is cumbersome, incomplete, and available from a limited number of laboratories. It requires testing parents for accurate interpretation, leading to healthcare inequity. Less severe forms are frequently misdiagnosed, and phenotype/genotype correlations incompletely understood. We explored whether emerging technologies could be leveraged to identify all pathogenic alleles of CAH, including phasing in proband-only cases. We targeted long-read sequencing outputs that would be practical in a clinical laboratory setting.

Both HiFi-based and nanopore-based whole-genome long-read sequencing datasets could be mined to accurately identify pathogenic single-nucleotide variants, full gene deletions, fusions creating non-functional hybrids between the gene and pseudogene (“30-kb deletion”), as well as count the number of RCCX modules and phase the resulting multimodular haplotypes. On the Hi-Fi data set of 6 samples, the PacBio Paraphase tool was able to distinguish nine different mono-, bi-, and tri-modular haplotypes, as well as the 30-kb and whole gene deletions. To do the same on the ONT-Nanopore dataset, we designed a tool, Parakit, which creates an enriched local pangenome to represent known haplotype assemblies and map ClinVar pathogenic variants and fusions onto them. With few labels in the region, optical genome mapping was not able to reliably resolve module counts or fusions, although designing a tool to mine the dataset specifically for this region may allow doing so in the future.

Both sequencing techniques yielded congruent results, matching clinically identified variants, and offered additional information above the clinical test, including phasing, count of RCCX modules, and status of the other module genes, all of which may be of clinical relevance. Thus long-read sequencing could be used to identify variants causing multiple forms of CAH in a single test.
IFNγ regulates MR1 transcription and antigen presentation
Authors: Huber ME , Larson EA , Lust TN , Heisler CM , Harriff MJ
Published: February 2025

Antigen presentation molecules play key roles in activating T cell immunity. Multiple complementary pathways are known to regulate classical MHC-I molecules at transcriptional, translational, and post-translational levels. Intracellular trafficking mechanisms dictating post-transcriptional regulation of MR1, the MHC Class I-like molecule which restricts MAIT cells, have been an area of focus; however, little is known aboutMR1transcriptional regulation. We demonstrate that, similar to classical MHC-I, interferons regulateMR1transcription. Treatment of airway epithelial cells (AEC) with recombinant IFNβ or IFNγ variably increasedMR1transcripts, while only IFNγ significantly increased surface MR1 expression and enhanced antigen presentation to MAIT cells. The MR1 promoter contains binding motifs for interferon regulatory factor 1 (IRF1), an important MHC-I transcription factor. IRF1 knockout reduced IFNγ-stimulated MR1 transcription, surface expression, and antigen presentation. Conversely, knockout of Nod-like Receptor family CARD domain containing 5 (NLRC5), a critical component of IFNγ-induced MHC-I transcription, did not significantly impact MR1 expression. These findings were corroborated in primary human AEC treated with IFNγ. In co-culture experiments, MAIT cells incubated withStreptococcus pneumoniae-infected primary AEC produced sufficient IFNγ to stimulate upregulation of MR1 expression. Our data support a model where IFNγ from activated MAIT cells or another source stimulates IRF1-dependent MR1 expression and antigen presentation, leading to greater MAIT cell activation. A robust MR1-dependent MAIT cell response may be beneficial for early infection responses, allowing minimal antigen stimulus to generate greater proinflammatory activity.
Effects of tree plantations on population and roosting ecology of an endemic agamid lizard in Western Ghats Biodiversity Hotspot
Authors: Gosavi Ninad , Lad Himanshu , Vijayan Jithin , Naniwadekar Rohit
Published: February 2025

Low-elevation wet tropical forests support herpetofaunal diversity but are increasingly replaced by monoculture tree plantations and have poor Protected Area coverage, leaving herpetofauna vulnerable. Research on how monoculture plantations affect reptile populations remains inconclusive, and the ecology of endemic species in these changing landscapes is poorly understood. We compared densities and roosting ecology ofMonilesaurus rouxii, an endemic agamid lizard, across low- and high-elevation forests and cashew and rubber plantations in the Western Ghats Biodiversity Hotspot using nocturnal transects. We found that low-elevation forests, despite poor Protected Area coverage, had significantly higher densities ofMonilesaurus rouxiithan high-elevation forests and cashew plantations. Roost site use did not differ significantly across the different land-use, indicating roost fidelity. However,Monilesaurus rouxiiexhibited ontogenetic shifts in roosting substrate and height. Our findings highlight the conservation importance of unprotected low-elevation forests, which are rapidly being converted to monoculture tree plantations. We show that plantation types may differ in their impacts on reptile populations. We also show the utility of nocturnal transects for population estimation of diurnal lizards.
Analysis of molecular and cellular bases of honey bee mushroom body development
Authors: Kamata Shuichi , Kubo Takeo , Kohno Hiroki
Published: February 2025

Honey bee mushroom bodies (MBs) comprise three class I Kenyon cell (KC) subtypes (lKC, mKC, and sKC) with distinct somata sizes and locations and gene expression profiles. While these KC subtypes have been suggested to function in different behavioral regulations, the molecular and cellular basis of their development remains obscure. Here, we showed that lKCs, mKCs, and sKCs are produced in that order at different pupal stages by labeling proliferating MB cells with 5-ethynil-2’-deoxyuridine at various pupal stages. RNA-sequencing analysis of FACS-sorted pupal MB cells identified genes that were upregulated in proliferating and non-proliferating MB cells, respectively. Furthermore,in situhybridization of some of these genes labeled the proliferating cells or young KCs in the pupal MBs. Our findings reveal the basic scheme of the molecular and cellular processes of honey bee MB development and suggest that they are at least partially different from those ofDrosophilaMB development.
Energy-conservation conditions in the saddle-point approximation for the strong-field ionization of atoms
Authors: Rook T. , Habibović D. , Faria C. Figueira de Morisson
Published: February 2025

Orbit-based methods are widespread in strong-field laser-matter interaction. They provide a framework in which photoelectron momentum distributions can be interpreted as the quantum interference between different semiclassical pathways the electron can take on its way to the detector, which brings with it great predictive power. The transition amplitude of an electron going from a bound state to a final continuum state is often written as multiple integrals, which can be computed either numerically or by employing the saddle-point method. If one computes the momentum distribution via a saddle-point method, then the obtained distribution is highly dependent on the time window from which the saddle points are selected for inclusion in the “sum over paths.” In many cases, this leads to the distributions not even satisfying the basic symmetry requirements and often containing many more oscillations and interference fringes than their numerically integrated counterparts. Using the strong-field approximation, we find that the manual enforcement of the energy-conservation condition on the momentum distribution calculated via the saddle-point method provides a unique momentum distribution which satisfies the symmetry requirements of the system and which is in a good agreement with the numerical results. We illustrate our findings using the example of the Ar atom ionized by a selection of monochromatic and bichromatic linearly polarized fields.

Published by the American Physical Society
2025
Bounds on the detection of Bell correlations with entangled ultracold atoms in optical lattices under occupation defects
Authors: Hernández Yanes T. , Bamaara Y. , Sinatra A. , Witkowska E.
Published: February 2025

Bell nonlocality stems from quantum correlations effectively identified using inequalities. Spin chains, simulated with ultracold atoms in optical lattices, Rydberg atoms in tweezer arrays, trapped ions, or molecules allow single-spin control and measurement. Therefore, they are suitable for studying fundamental aspects of these correlations and nonlocality. Occupation defects, such as vacancies or multiple atoms occupying a single site due to imperfect system preparation, limit the detection of Bell correlations. We study their effects with the help of a simplified toy model parametrized by the probability p of having a single occupation for a given site. Within this model, and for entangled systems obtained by one-axis twisting evolution from an initial factorized state, we derive two Bell inequalities, one based on many-site correlations and the other on two-site correlations, and identify the smallest probability p that allows the Bell inequalities violation to be detected. We then consider two physical realizations using entangled ultracold atoms in optical lattices where the parameter p is related to a nonunitary filling factor and nonzero temperature. We test the predictions of the toy model against exact numerical results.

Published by the American Physical Society
2025
Hadronic weak decays of charmed baryons in the topological diagrammatic approach: An update
Authors: Cheng Hai-Yang , Xu Fanrong , Zhong Huiling
Published: February 2025

There exist two distinct ways in realizing the approximate SU(3) flavor symmetry of QCD to describe the two-body nonleptonic decays of charmed baryons: the irreducible SU(3) approach (IRA) and the topological diagram approach (TDA). The TDA has the advantage that it is more intuitive, graphic, and easier to implement model calculations. We perform a global fit to the currently available data of two-body charmed baryon decays within the framework of the TDA and IRA. The number of the minimum set of tensor invariants in the IRA and the topological amplitudes in the TDA is the same, namely, five in the tree-induced amplitudes and four in the penguin amplitudes. Since we employ the new LHCb measurements to fix the sign ambiguity of the decay parameters β and γ, the fit results for the magnitudes of S- and P-wave amplitudes and their phase shift δP−δS in both the TDA and IRA are more trustworthy than our previous analyses with uncertainties substantially improved. These results can be tested in the near future. The perspective of having direct CP violation in the charmed baryon sector at the per mille level is briefly discussed.

Published by the American Physical Society
2025
Chiral effective theory of scalar and vector diquarks revisited
Authors: Kim Yonghee , Oka Makoto , Suzuki Kei
Published: February 2025

Chiral effective theory of light diquarks is revisited. We construct an effective Lagrangian based on the linear representation of three-flavor chiral symmetry. Here, we focus on the effect of a chiral and U(1)A symmetric term originated from an eight-point quark interaction. From this model, we obtain the mass formulas of scalar, pseudoscalar, vector, and axial-vector diquarks, which also describe the dependence of diquark masses on the spontaneous chiral symmetry breaking and the U(1)A anomaly. We regard singly heavy baryons as two-body systems composed of one heavy quark and one diquark and then predict the fate of the mass spectrum and the strong decay widths under chiral symmetry restoration.

Published by the American Physical Society
2025
Electrical conductivity of the quark-gluon plasma in the presence of strong magnetic fields
Authors: Almirante Giorgio , Astrakhantsev Nikita , Braguta V. V. , D’Elia Massimo , Maio Lorenzo , Naviglio Manuel , Sanfilippo Francesco , Trunin Anton
Published: February 2025

We compute the electrical conductivity of the strongly interacting medium in the presence of strong magnetic background fields, eB=4, 9  GeV2, and for different values of the temperature, both in the confined and in the deconfined quark-gluon plasma (QGP) phase. The conductivity is obtained from the Euclidean lattice time correlator of the electrical current, computed on gauge configurations sampled from Monte-Carlo simulations of an improved staggered discretization of Nf=2+1 QCD. We perform the inverse Laplace transform of the correlator adopting a recently proposed version of the standard Backus-Gilbert procedure for the inversion. The results obtained in the QGP phase show a sizable enhancement of the conductivity in the direction parallel to the magnetic field, as well as a suppression in the direction orthogonal to it. The enhancement can interpreted through various different mechanisms, typically involving the chiral anomaly, among which the chiral magnetic effect (CME): for this reason we try to interpret our observations based on a CME-inspired , we extract the relaxation time of this process, extrapolate it to the continuum limit and compare it to previous results, finding it lower than expected in the explored range of temperatures.

Published by the American Physical Society
2025
Quantum chaos in random Ising networks
Authors: Grabarits András , Swain Kasturi Ranjan , Heydari Mahsa Seyed , Chandarana Pranav , Gómez-Ruiz Fernando J. , del Campo Adolfo
Published: February 2025

We report a systematic investigation of universal quantum chaotic signatures in the transverse field Ising model on an Erdős-Rényi network. This is achieved by studying local spectral measures such as the level spacing and the level velocity statistics. A spectral form factor analysis is also performed as a global measure, probing energy level correlations at arbitrary spectral distances. Our findings show that these measures capture the breakdown of chaotic behavior upon varying the connectivity and the strength of the transverse field in various regimes. We demonstrate that the level spacing distribution and the spectral form factor signal this breakdown for sparsely and densely connected networks. The velocity statistics capture the surviving chaotic signatures in the sparse limit. However, these integrablelike regimes extend over a vanishingly small segment in the full range of connectivity. Our work elucidates the emergence of quantum chaos in relation to network topology, establishing a bridge between many-body physics and network theory.

Published by the American Physical Society
2025