bluuebunny/crossref_metadata_2025 huggingface dataset:
PET/computed tomography radiomics combined with clinical features in predicting sarcopenia and prognosis of diffuse large B-cell lymphoma
Authors: Wang Fanghu , Chen Yang , Tan Xiaoyue , Han Xu , Lu Wantong , Lu Lijun , Yuan Hui , Jiang Lei
Published: November 2024

Background

The study aimed to assess the role of 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) radiomics combined with clinical features using machine learning (ML) in predicting sarcopenia and prognosis of patients with diffuse large B-cell lymphoma (DLBCL).

Methods

A total of 178 DLBCL patients (118 and 60 applied for training and test sets, respectively) who underwent pretreatment 18F-FDG PET/CT were retrospectively enrolled. Clinical characteristics and PET/CT radiomics features were analyzed, and feature selection was performed using univariate logistic regression and correlation analysis. Sarcopenia prediction models were built by ML algorithms and evaluated. Besides, prognostic models were also developed, and their associations with progression-free survival (PFS) and overall survival (OS) were identified.

Results

Fourteen features were finally selected to build sarcopenia prediction and prognosis models, including two clinical (maximum standard uptake value of muscle and BMI), nine PET (seven gray-level and two first-order), and three CT (three gray-level) radiomics features. Among sarcopenia prediction models, combined clinical-PET/CT radiomics features models outperformed other models; especially the support vector machine algorithm achieved the highest area under curve of 0.862, with the sensitivity, specificity, and accuracy of 79.2, 83.3, and 78.3% in the test set. Furthermore, the consistency index based on the prognostic models was 0.753 and 0.807 for PFS and OS, respectively. The enrolled patients were subsequently divided into high-risk and low-risk groups with significant differences, regardless of PFS or OS (P < 0.05).

Conclusion

ML models incorporating clinical and PET/CT radiomics features could effectively predict the presence of sarcopenia and assess the prognosis in patients with DLBCL.
A narrative review on the performance and outcomes of penile and scrotal surgery in the ambulatory setting
Authors: Shah Jainik , Fidel Maximilian G. , Almuhanna Ahmed Mousa , Bal Dhiraj S. , Patel Premal
Published: November 2024

Purpose of review

Following the COVID-19 pandemic, surgical wait times have surged, creating a backlog in elective urological procedures. This review aims to address the need to explore ambulatory care for penile and scrotal surgeries, which can offer benefits by shifting these procedures away from traditional inpatient settings.

Recent findings

Recent studies confirm the safety and efficacy of performing penile and scrotal procedures in an ambulatory setting using local anesthesia (LA) or loco-sedative techniques. Of 616 reviewed cases, over 90% of patients expressed high satisfaction with LA and reported minimal postoperative complications. Pain management advancements, particularly the use of liposomal bupivacaine, reduced the need for opioids postoperatively. Importantly, no intraoperative complications or hospital admissions were reported, and adverse events were managed conservatively. The data highlighted in this review supports a move towards outpatient surgeries as a safe alternative to inpatient care for select cases.

This review highlights the strong potential for ambulatory urological surgeries to alleviate surgical backlogs significantly, while reducing strain on hospital resources, and maintaining high levels of patient satisfaction. As evidence continues to grow on the safety, feasibility, and effectiveness of LA in office-based procedures, expanding ambulatory urological will be quintessential in modernizing patient care and reducing healthcare burdens.
National Incidence of Nurse Suicide and Associated Features
Authors: Davidson Judy E. , Makhija Hirsh , Lee Kelly C. , Barnes Arianna , Richardson Marcus Groner , Choflet Amanda , Ali Tatyana , Zisook Sidney
Published: November 2024

OBJECTIVES

The aim of this study was to estimate the national incidence of nurse suicide.

BACKGROUND

Nurses are at a higher risk of suicide than nonnurses; however, data have been limited since 2018.

METHODS

This study used a retrospective cohort design using 2017–2021 National Violent Death Reporting System suicides.

RESULTS

Female nurses had higher suicide rates than female nonnurses in 2018 (incidence rate ratio, 1.21 [95% confidence interval (CI), 1.05-1.39]), 2019 (1.41 [95% CI, 1.23-1.60]), 2020 (1.26 [95% CI, 1.08-1.45]), and 2021 (1.35 [95% CI, 1.17-1.55]), whereas male nurses were comparable with male nonnurses. Nurses had higher odds of mental health problems (adjusted odds ratio, 1.28 [95% CI, 1.13-1.46], P < .001), job problems (1.60 [95% CI, 1.33-1.92], P < .001), and use of poisoning (1.54 [95% CI, 1.37-1.74], P < .001). Nurses had higher odds of using opioids, cardiovascular/diabetic agents, and drugs not prescribed for home use.

CONCLUSION

Female nurses are at a higher risk of suicide than other females. Multimodal nurse suicide prevention strategies remain indicated.
Assessment of Facility Readiness for Pediatric Emergency and Critical Care Utilizing a 2-Phase Survey Conducted in Six Hospitals in Uganda and Cameroon: A Quality Improvement Study
Authors: Hwang Bella , Trawin Jessica , Dzelamunyuy Suiyven , Wiens Matthew O. , Tagoola Abner , Businge Stephen , Jabornisky Roberto , Nwankwor Odiraa , Karlovich Gabrielle , Oguonu Tagbo , Talla Emmanuella , Novakowski Stefanie K. , Fung Jollee S.T. , West Nicholas , Ansermino J. Mark , Kissoon Niranjan
Published: November 2024

Objectives

Each year, 5.3 million children under 5 years of age die in low-resource settings, often due to delayed recognition of disease severity, inadequate treatment, or a lack of supplies. We describe the use of a comprehensive digital facility-readiness survey tool, recently developed by the Pediatric Sepsis Data CoLaboratory, which aims to identify target areas for quality improvement related to pediatric emergency and critical care.

Methods

Facility-readiness surveys were conducted at six sub-Saharan African hospitals providing pediatric emergency and critical care in Uganda (n = 4) and Cameroon (n = 2). The tool is a 2-phase survey to assess readiness to provide pediatric essential emergency and critical care: (1) an “environmental scan,” focusing on infrastructure, availability, and functionality of resources, and (2) an “observational scan” assessing the quality and safety of care through direct observation of patients receiving treatment for common diseases. Data were captured in a mobile application and the findings analyzed descriptively.

Results

Varying levels of facility readiness to provide pediatric emergency care were observed. Only 1 of 6 facilities had a qualified staff member to assess children for danger signs upon arrival, and only 2 of 6 had staff with skills to manage emergency conditions. Only 21% of essential medicines required for pediatric emergency and critical care were available at all six facilities. Most facilities had clean running water and soap or disinfectants, but most also experienced interruptions to their electricity supply. Less than half of patients received an appropriate discharge note and fewer received counseling on postdischarge care; follow-up was arranged in less than a quarter of cases.

Conclusions

These pilot findings indicate that facilities are partially equipped and ready to provide pediatric emergency and critical care. This facility-readiness tool can be utilized in low-resource settings to assist hospital administrators and policymakers to determine priority areas to improve quality of care for the critically ill child.
Time Since Injury Is Key to Modeling Trends in Aging and Overall Functioning of Persons With Spinal Cord Injury
Authors: Sabariego Carla , Fellinghauer Carolina , Hodel Jsabel , Ehrmann Cristina , Eriks-Hoogland Inge , Seijas Vanessa , Stucki Gerold
Published: November 2024

Objective

The aim of the study is to model the health indicator of functioning for persons with spinal cord injury or disorder living in Switzerland in the long-term context, considering chronological age, time since injury, and age at injury.

Design

This is a longitudinal analysis of three waves of a community survey. An interval-scaled functioning metric was constructed using modern test theory. Random effects within-between mixed models were used to investigate trends in functioning over time.

Results

Persons with complete injuries have lower levels of functioning than persons with incomplete injuries, and persons with complete tetraplegia have the lowest levels of functioning. The person’s age when injured, the level and completeness of the injury, the presence of secondary health conditions, and various combinations of these factors significantly influenced how functioning changed over time.

Conclusions

Our study shows that chronological age is not necessarily the best time variable for understanding the aging process of people with spinal cord injury in terms of changes in functioning over time and that modeling functioning over time since injury provides important insights into how functioning of people with complete or incomplete injuries declines with increasing time living with the injury.
Predictors of Injection Visit Adherence in Those Receiving Injectable Cabotegravir/Rilpivirine
Authors: Hill Lucas , Yin Jeffrey , Patel Nimish , Abulhosn Kari , Suarez Elvia , Karim Afsana , Bamford Laura
Published: November 2024

Background:

There is limited data evaluating potential predictors of adherence to injection visits and the impact of late injections on viral suppression in those receiving long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) for the treatment of HIV.

Methods:

A retrospective cohort study was conducted among adult people with HIV receiving LAI CAB/RPV for at least 6 months between May 2021 and August 2023. Data collected included demographics, office visit no-shows 1 year before switching to LAI CAB/RPV, injection visit no-shows, injections outside the dosing window, and virologic outcomes. Cox-proportional hazards regression was performed to evaluate predictors of no-show to injection visits or late injections.

Results:

Included were 287 people with HIV with a median follow-up time (interquartile range) of 450 days (344–548 days). Younger age [HR 0.97 (95% CI: 0.95 to 0.98)] and ≥1 office visit no-show in the year before switching to LAI CAB/RPV [HR 2.03 (1.32 to 3.12]) were associated with having a no-show to an injection visit (32.1%). Male sex assigned at birth [HR 9.18 (1.26 to 66.9)] with a trend toward younger age [HR 0.98 (0.95 to 1.0)] were associated with having a late injection (15.3%). There was no relationship between late injections and having a detectable viral load or virologic failure (n = 3) after switching to LAI CAB/RPV.

Conclusions:

Having office visit no-shows before switching to LAI CAB/RPV was associated with missed injection visits, and younger age was associated with both missed injection visits and late injections. Resources to reduce and manage missed injection appointments need to be considered when implementing LAI CAB/RPV.
Cancer-Specific Integrin Imaging With 68Ga-Trivehexin
Authors: Singhal Tejasvini , Agrawal Kanhaiyalal , Mandal Srijani , Parida Girish Kumar
Published: November 2024

68Ga-Trivehexin is a novel radiotracer binding to “cancer-specific integrin αvβ6.” 68Ga-Trivehexin has high specificity for tumor cells and, thus, has the potential to replace 18F-FDG PET/CT due to its limited specificity in the head and neck cancer. Here, we present one case of papillary thyroid carcinoma, where 68Ga-Trivehexin PET CT demonstrated accurate staging compared with 18F-FDG PET/CT.
Identification of actionable genetic variants in 4,198 Scottish volunteers from the Viking Genes research cohort and implementation of return of results
Authors: Kerr Shona M. , Klaric Lucija , Muckian Marisa D. , Johnston Kiera , Drake Camilla , Halachev Mihail , Cowan Emma , Snadden Lesley , Dean John , Zheng Sean L. , Thami Prisca K. , Ware James S. , Tzoneva Gannie , Shuldiner Alan R. , Miedzybrodzka Zosia , Wilson James F.
Published: November 2024

The benefits of returning clinically actionable genetic results to participants in research cohorts are accruing, yet such a genome-first approach is challenging. Here, we describe the return of such results in two founder populations from Scotland. Between 2005 and 2015, we recruited >4,000 adults with grandparents from Orkney and Shetland into the Viking Genes research cohort. Return of genetic data was not offered at baseline, but in 2023 we sent invitations for consent to return of actionable genetic findings to participants. We generated exome sequence data from 4,198 participants, and used the ACMG v3.2 list of 81 genes, ClinVar review and pathogenicity status, plus manual curation, to develop a pipeline to identify potentially actionable variants. We identified 104 individuals (2.5%) carrying 108 actionable genotypes at 39 variants in 23 genes, and validated these. Working with the NHS clinical genetics service, which provided genetic counselling and clinical verification of the research results, and after expert clinical review, we notified 64 consenting participants (or their next of kin) of their actionable genotypes. Ten actionable variants across seven genes (BRCA1, BRCA2, ATP7B, TTN, KCNH2, MUTYH, GAA) have risen 50 to >3,000-fold in frequency through genetic drift in ancestral island localities. Viking Genes is one of the first UK research cohorts to return actionable findings, providing an ethical and logistical exemplar of return of results. The genetic structure in the Northern Isles of Scotland, with multiple founder effects, provides a unique opportunity for a tailored approach to primary and secondary prevention through genetic screening.
Global estimates of lives and life-years saved by COVID-19 vaccination during 2020-2024
Authors: Ioannidis John P.A. , Pezzullo Angelo Maria , Cristiano Antonio , Boccia Stefania
Published: November 2024

Importance

Estimating global lives and life-years saved is important to put into perspective the benefits of COVID-19 vaccination. Prior studies have focused mainly on the pre-Omicron period or only on specific regions, lack crucial life-year calculations, and often depend on strong modeling assumptions with unaccounted uncertainty.

Observations

We aimed to calculate the lives and life-years saved by COVID-19 vaccination worldwide from the onset of the vaccination campaigns and until October 2024. We considered different strata according to age; community-dwelling and long-term care residence status; pre-Omicron and Omicron periods; and vaccination before and after a SARS-CoV-2 infection. In the main analysis, 2.533 million deaths were averted (1 death averted per 5,400 vaccine doses administered). Eighty-two percent were among people vaccinated before any infection, 57% were in the Omicron period, and 90% pertained to people 60 years and above. Sensitivity analyses suggested 1.4 to 4.0 million lives saved. Some sensitivity analyses showed preponderance of the benefit during the pre-Omicron period. We estimated 14.8 million life-years saved (1 life-year saved per 900 vaccine doses administered). Sensitivity range was 7.4-23.6 million life-years. Most life-years saved (76%) were in people over 60 years old, but long-term care residents contributed only 2% of the total. Children and adolescents (0.01% of lives saved and 0.1% of life-years saved) and young adults 20-29 years old (0.07% of lives saved and 0.3% of life-years saved) had very small contributions to the total benefit.

Conclusions and relevance

Based on a number of assumptions, these estimates are substantially more conservative than previous calculations focusing mostly on the first year of vaccination, but they still clearly demonstrate a major overall benefit from COVID-19 vaccination during 2020-2024. The vast majority of benefit in lives and life-years saved was secured for a portion of the elderly minority of the global population.
Validation of real-world actigraphy to capture post-stroke motor recovery
Authors: Lohse Keith R. , Miller Allison E. , Bland Marghuretta D. , Lee Jin-Moo , Lang Catherine E.
Published: November 2024

Stroke is a leading cause of long-term disability, but advances for rehabilitation have lagged those for acute treatment. Large biological studies (e.g., “omics”-based approaches) may offer mechanistic insights for recovery, but to enable those studies, researchers need to collect detailed recovery phenotypes at scale, e.g., in thousands of people with minimal burden for participants and researchers. This study investigates the concurrent validity between remotely collected wearable sensor data and clinical assessments of motor recovery post-stroke. We specifically focus on the “use ratio”, which is the activity level of the paretic arm relative to the non-paretic arm, measured via bilateral wrist-worn accelerometers. Utilizing a large, harmonized multi-site dataset of adults with stoke, we analyzed cross-sectional (N=198) and longitudinal (N=98) changes in use ratio, the Action Research Arm Test (ARAT) and the Fugl-Meyer Assessment upper extremity subscale (FM-UE). Our findings indicate strong concurrent validity of the use ratio and the ARAT, and the use ratio and the FM-UE both cross-sectionally (i.e.,differencesbetween people) and longitudinally (i.e.,changeswithin a person). Notably, while the use ratio strongly correlated with FM-UE and ARAT initially, the strength of these correlations reduced over time. This decreasing correlation might be explained by the increasing influence that personal and environmental factors play as recovery progresses. Additionally, these correlations were also stronger for the use ratio than for hours of activity for the paretic/nonparetic arm alone, suggesting that it is specifically asymmetry of activity that correlates with clinical measures. Thus, the use ratio is an efficient and clinically valid measure of motor recovery post-stroke that can be deployed at scale to collect biologically meaningful phenotypes.
Inferring temporal trends of multiple pathogens, variants, subtypes or serotypes from routine surveillance data
Authors: Eales Oliver , Windecker Saras M. , McCaw James M. , Shearer Freya M.
Published: November 2024

Estimating the temporal trends in infectious disease activity is crucial for monitoring disease spread and the impact of interventions. Surveillance indicators routinely collected to monitor these trends are often a composite of multiple pathogens. For example, ‘influenza-like illness’ — routinely monitored as a proxy for influenza infections — is a symptom definition that could be caused by a wide range of pathogens, including multiple subtypes of influenza, SARS-CoV-2, and RSV. Inferred trends from such composite time series may not reflect the trends of any one of the component pathogens, each of which can exhibit distinct dynamics. Although many surveillance systems routinely test a subset of individuals contributing to a surveillance indicator — providing information on the relative contribution of the component pathogens — trends may be obscured by time-varying testing rates or substantial noise in the observation process. Here we develop a general statistical framework for inferring temporal trends of multiple pathogens from routinely collected surveillance data. We demonstrate its application to three different surveillance systems covering multiple pathogens (influenza, SARS-CoV-2, dengue), locations (Australia, Singapore, USA, Taiwan, UK), scenarios (seasonal epidemics, non-seasonal epidemics, pandemic emergence), and temporal reporting resolutions (weekly, daily). This methodology is applicable to a wide range of pathogens and surveillance systems.
A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia
Authors: Viz-Lasheras Sandra , Gómez-Carballa Alberto , Pardo-Seco Jacobo , Bello Xabier , Rivero-Calle Irene , Dacosta Ana Isabel , Kaforou Myrsini , Coote Dominic , Cunnington Aubrey J. , Emonts Marieke , Herberg Jethro A. , Wright Victoria J. , Carrol Enitan D. , Paulus Stephane C. , Zenz Werner , Kohlfürst Daniela S. , Van der Flier Michiel , de Groot Ronald , Schlapbach Luregn J. , Agyeman Philipp , Pollard Andrew J. , Fink Colin , Kuijpers Taco T. , Anderson Suzanne , Calvo Cristina , Martínez-Padilla María del Carmen , Pérez-Aragón Ana , Gómez-Sánchez Esteban , Valencia-Ramos Juan , Giménez-Sánchez Francisco , Alonso-Quintela Paula , Moreno-Galarraga Laura , von Both Ulrich , Pokorn Marko , Zavadska Dace , Tsolia María , Vermont Clementien L. , Moll Henriëtte A. , Levin Michael , Martinón-Torres Federico , Salas Antonio
Published: November 2024

Pneumonia stands as the primary cause of death among children under five, yet current diagnosis methods often result in inadequate or unnecessary treatments. Our research seeks to address this gap by identifying host transcriptomic biomarkers in the blood of children with definitive viral and bacterial pneumonia. We performed RNA sequencing on 192 prospectively collected whole blood samples, including 38 controls and 154 pneumonia cases, uncovering a 5-transcript signature (genesFAM20A,BAG3,TDRD9,MXRA7andKLF14) that effectively distinguishes bacterial from viral pneumonia (AUC: 0.95 [0.88–1.00]) Initial validation using combined definitive and probable cases yielded an AUC of 0.87 [0.77–0.97], while full validation in a new prospective cohort of 32 patients achieved an AUC of 0.92 [0.83–1]. This robust signature holds significant potential to enhance diagnostics accuracy for pediatric pneumonia, reducing diagnostic delays and unnecessary treatments, and potentially transforming clinical practice.
Healthcare Equity in Epilepsy Surgery: Equivalent Outcomes Between NAEC-IV Public Safety-Net and Tertiary Academic Centers in a Major Metropolitan Area
Authors: Lam Jordan , Mehta Vivek , Russin Jonathan , Millett David , Shaw Susan , Liu Lauren , Lee Brian , Kalayjian Laura , Armacost Michelle , Gong Hui , Heck Christi , Lee Darrin , Liu Charles
Published: November 2024

Access to and delivery of quality surgical epilepsy care remains a challenge in both safety-net and private hospital systems. Underserved populations are more likely to utilize safety-net hospital systems, but there are few data on epilepsy surgery outcomes in this setting. We aimed to analyze and compare surgical epilepsy care in a safety-net versus private hospital system. We prospectively collected evaluation and treatment data in patients undergoing resective surgery for epilepsy at a safety-net hospital system and a collaborating private hospital system between 2010-2017. Seizure characteristics, pre-surgical evaluation, perioperative complications, and seizure outcomes were prospectively recorded. Data from 102 patients in the safety-net and 145 patients in the private hospital system were analyzed. There were higher proportions of African American (p=.02) and Hispanic patients (p= .03) in the safety-net hospital system. There was no difference in mean time from epilepsy onset to surgery between groups (p=.54). The presurgical evaluation was equivalent (p>.18), except for more frequent use of magnetoencephalography in the private system (p=.02). Seizure freedom outcomes were excellent, and complication rates were low with no significant differences between groups (p=.95 and p>.22, respectively). However, patients from safety-net hospital systems were more likely to be lost to follow up (p=.04). Quality and equitable surgical epilepsy care can be delivered in a safety-net hospital system despite the higher-minority demographics and intrinsic factors of safety-net hospitals. Partnership of safety-net hospital systems with established comprehensive epilepsy centers and the expansion of these services is essential for healthcare equity in modern epilepsy care.
Diagnostic Accuracy of Artificial Intelligence in Classifying HER2 Status in Breast Cancer Immunohistochemistry Slides and Implications for HER2-Low Cases: A Systematic Review and Meta-Analysis
Authors: Arruda Navarro Albuquerque Daniel , Trotta Vianna Matheus , Alencar Fernandes Sampaio Luana , Vasiliu Andrei , Cunha Neves Filho Eduardo Henrique
Published: November 2024

Breast cancer with overexpression of the Human Epidermal Growth Factor Receptor 2 (HER2) accounts for 15-20% of cases and is associated with poor outcomes. Although trastuzumab-deruxtecan (T-DXd) has traditionally demonstrated survival benefits in metastatic HER2-positive patients, the DESTINY-Breast04 trial expanded its effectiveness to those with immunohistochemistry (IHC) scores of 1+, and 2+ with negative in situ hybridisation, a subset of patients that has since been termed “HER2-low”. Accurate differentiation of HER2 scores has now become crucial. However, visual IHC scoring is labour-intensive and prone to high interobserver variability. AI has emerged as a promising tool in diagnostic medicine, particularly within histopathology. This study assesses AI’s ability to identify patients eligible for T-DXd and its performance in accurately classifying HER2 scores. Electronic searches were conducted in MEDLINE, EMBASE, Scopus, and Web of Science up to May 2024. Eligibility criteria were limited to studies evaluating the performance of AI compared to pathologists in classifying HER2 utilising IHC slides. Metaanalysis was performed using the bivariate random-effects model to estimate pooled sensitivity, specificity, concordance, and area under the curve (AUC). To explore sources of heterogeneity, subgroup analysis and meta-regression were performed. Risk of bias was assessed using QUADAS-AI tool. We analysed 25 contingency tables across thirteen included publications, showing excellent AI accuracy in predicting T-DXd eligibility, with a pooled sensitivity of 0.97 [95%CI 0.96-0.98], specificity of 0.82 [95%CI 0.73-0.88], and AUC of 0.98 [95%CI 0.96-0.99]. In the individual scores analysis, AI performed better particularly in scores 2+ and 3+. Substantial heterogeneity was observed, and meta-regression revealed better performance with deep learning and patch-based analysis, while performance declined in externally validated and those utilising commercially available algorithms. Our findings indicate that AI holds promising potential in accurately identifying HER2-low patients and excels in distinguishing 2+ and 3+ scores. Upcoming validation studies should focus on enhancing AI’s precision in the 0-1+ range and improving the reporting of clinical and pre-analytical data to standardise samples characteristics, ensuring models are more comparable to each other. This review highlights that deep learning advancements are driving automation, requiring pathologists to adapt and integrate this technology into their workflow.
Evaluation of DNA-poli: study protocol of a randomised controlled trial to assess a digital platform for family cascade genetic testing and predictive genetic counselling
Authors: van Lingen Marlies N. , Meulenkamp Janine V. , Siemelink Marten A. , Beinema Tessa C. , Klaassen Randy , Heylen Dirk K.J. , van Tintelen J. Peter , van den Heuvel Lieke M.
Published: November 2024

Introduction

The present uptake of predictive genetic counselling among at-risk relatives (ARRs) for cardiogenetic diseases is suboptimal with 40-50% of ARRs being tested after one to three years post- disclosure. Digital technologies are increasingly proposed to improve accessibility, efficiency, and uptake of predictive genetic counselling and, if desired, predictive genetic testing. Therefore, DNA- poli was developed: a digital platform providing family communication support and pre- and post-test genetic counselling for ARRs. The online DNA-poli aims to decrease the threshold for ARRs to seek genetic counselling without compromising the quality of care while increasing the efficiency of genetic care. Here, we describe the study protocol for a randomised controlled trial evaluating DNA- poli in clinical practice.

Methods and analysis

A non-inferiority multicentre randomised controlled trial with parallel-group design will be conducted. The intervention group using the DNA-poli platform will be compared to a control group receiving regular counselling. Probands with hypertrophic or dilated cardiomyopathy in whom a (likely) pathogenic variant in specific genes with definitive gene-disease validity is identified, will be included like their ARRs and physicians. The primary outcome is the uptake of cardiogenetic counselling six months post-disclosure with an extended follow-up of one year and stakeholders’ experiences. Secondary outcomes are informed decision-making in ARRs, empowerment, and the satisfaction of all stakeholder groups. In addition, the efficiency of consultations and the genetic care process will be analysed. Descriptive and inferential statistics will be performed to analyse data.

Ethics and dissemination

This study protocol was exempted from approval by the Medical Ethical Committee NedMec because the Act of Medical Research Involving Human Subject (WMO) was not applicable (no. 23-066/C). Study findings will be shared with stakeholders, published in journals, and will be presented at both international and national conferences.

Registration detailsNCT06431425ClinicalTrials.gov
Completion of multi-dose COVID-19 vaccines and the associated factors among adolescents and adults in two urban informal settlements in Nairobi, Kenya
Authors: Ng’oda Maurine , Izudi Jonathan , Otieno Collins , Mwanga Daniel , Sanya Richard E. , Ziraba Abdhalah
Published: November 2024

Completion of vaccine doses is essential for robust immunity and long-term protection against specific diseases. This study aimed to investigate factors associated with the completion of multi-dose COVID-19 vaccines (MDV) among adolescents and adults in two informal urban settlements in Nairobi, Kenya. We analyzed data from the Kenya Multisite Integrated Serosurveillance (KEMIS) project. We defined completion of MDV as receiving an additional COVID-19 vaccine dose between weeks 6 and 8 following the first COVID-19 vaccination shot. We applied the modified Poisson regression model with robust standard errors to determine the factors that were independently associated with the completion of MDV. We analyzed data from 402 individuals aged 14-90 years and found that the completion rate for MDV was 85.3%. In the adjusted analysis, participants aged ≥60 years (adjusted prevalence risk ratio [aPR] 1.30, 95% confidence interval [CI] 1.05-1.60) and those who recommended the COVID-19 vaccine to others (aPR 1.40, 95% CI 1.00-1.96) were significantly more likely to complete MDV. Individuals aged 25-59 years (aPR 1.22, 95% CI 0.99-1.50), those who perceived themselves as being at risk for COVID-19 (aPR 1.09, 95% CI 0.99-1.19), and those who had access to healthcare during the pandemic tended to have a higher completion of MDV. Overall, the MDV completion rate is relatively high, however, public health interventions should endeavor to target those being left behind such as younger individuals and those hesitant about vaccination.
High Temperature and Microbiome Conditions Affect Gene Expression in Soybean
Authors: Van der Laan Liza , Elango Dinakaran , Ferela Antonella , O’Rourke Jamie A. , Singh Asheesh K.
Published: November 2024

Heat stress is increasingly a problem in global agriculture production, both in increasing occurrences and extended durations. Understanding the molecular mechanisms of the soybean heat stress response is essential for breeding heat tolerant soybeans. Plant associated microbiomes are known to mitigate adverse effects from abiotic stress. Soybean heat stress studies have primarily focused on response to short periods of stress, and how soybean responds on a transcriptional level to a soil microbiome is poorly understood. We hypothesize a soil microbiome may help soybean survive long-term heat stress exposure. We used RNA-seq to measure the transcriptional responses in four soybean exposed to two temperature regimes and grown in two soil microbiome conditions. We identified unique responses to temperature based on the soil microbiome conditions and to the different genotypes, with fewer changes across genotypes in response to a soil microbiome. Our findings provide insights on the interaction of soil microbiome with heat stress response in soybean and identify gene targets to further study the soybean heat stress tolerance with applications to develop improved varieties.
EEG connectome-based predictive modeling of nonverbal intelligence level in healthy subjects
Authors: Pashkov Anton , Dakhtin Ivan , Feklicheva Inna , Shmotina Julia , Hassan Mahmoud
Published: November 2024

Intelligence is increasingly recognized as a critical factor in successful behavioral and emotional regulation. Neuroimaging techniques coupled with machine learning algorithms have proven to be valuable tools for uncovering the neural foundations of individual cognitive abilities. Nevertheless, current electroencephalograph (EEG) studies primarily focus on classification tasks to predict the intelligence category of subjects (e.g., high, medium, or low intelligence), rather than providing quantitative intelligence level forecasts. Furthermore, the outcomes obtained are significantly impacted by the specific data processing pipeline chosen, which could potentially compromise result generalizability. In this study, we implemented a connectome-based predictive modeling approach on high-density resting state EEG data from healthy participants to predict their nonverbal intelligence level. This method was applied to three independently collected datasets (N = 255) with different functional connectivity methods, parcellation atlases, threshold p-values and curve fitting orders used to ensure the reliability of the findings. We found that the prediction accuracy expressed in terms of R² varied significantly depending on the processing pipeline configuration, ranging from negative R2values up to 0.27. The most consistent results across datasets were found in the alpha frequency band. Furthermore, we employed a computational lesioning approach to identify the valuable edges that made the most significant contribution to predicting intelligence. This analysis highlighted the crucial role of frontal and parietal regions in complex cognitive computations. Overall, these findings support and expand upon previous research, underscoring the close relationship between alpha rhythm characteristics and cognitive functions and emphasizing the critical consideration of method selection in result evaluation.
Potassium ferric oxalate nanoparticles prevent human blood clotting and thrombosis in a mouse model
Authors: Yenurkar Devyani , Choudhary Ankit , Shrivastava Anoushka , Pragya  , Mandal Snehasish , Soni Priyanshu , Pradhan Lipi , Singh Ankur , Sarkar Arnab , Mukherjee Sudip
Published: November 2024

Blood clot creates occlusion in the veins and arteries, which leads to pernicious effects. Here, the anticoagulation properties of potassium ferric oxalate nanoparticles (KFeOx-NPs) in human blood were demonstrated for blood clot management. The mechanism involves the chelation of calcium ions from the blood by the oxalate present in the KFeOx-NPs. Various commercial assays were used to determine the clotting time for the KFeOx-NPs and identified the hindrance in activating factor XII in the intrinsic pathway. We used animal models to show toxicity and biodistribution profiles and determined the safety and efficacy. Intravenously injected KFeOx-NPs increased clotting time and thrombosis prevention in a mouse model confirmed by ultrasound and the power Doppler images. Coating catheters with KFeOx-NPs prevents clot formation with reduced protein attachment when incubated with blood, enhancing blood flow properties. In biological applications, KFeOx-NPs may improve the long-term prevention of blood clot formation and enhance the efficiency of medical devices.

TOC

PVP-stabilized novel potassium ferric oxalate nanoparticles were synthesized for the application of blood clot management and thrombosis prevention.
A high-resolution analysis of arrestin2 interactions responsible for CCR5 endocytosis
Authors: Petrovic Ivana , Desai Samit , Isaikina Polina , Abiko Layara Akemi , Spang Anne , Grzesiek Stephan
Published: November 2024

Clathrin-mediated endocytosis (CME) is crucial for regulating G protein-coupled receptors (GPCRs) via phosphorylation-dependent arrestin interactions. The interplay between receptor phosphorylation and arrestin coupling to the CME machinery has only been explored for a few GPCRs. Here we have investigated the CME of the chemokine receptor CCR5 induced by native and engineered CCL5 ligands. Upon CCL5 agonist stimulation, arrestin2 translocates to CCR5 at the plasma membrane forming a long-lived CCR5-arrestin2 complex that is internalized but does not reach the lysosomes. Solution NMR revealed that arrestin2 interacts weakly with clathrin through a single binding site, independent of arrestin2 activation by phosphorylated CCR5 C-terminal tail peptides. In contrast, the arrestin2-AP2 interaction is stronger and requires arrestin2 activation depending quantitatively on the CCR5 C-terminal tail phosphorylation. Thein vitroresults are corroborated by cellular assays, which establish a crucial role of the arrestin2 interaction with AP2, but not with clathrin for CCR5 internalization. These findings give insights how receptor phosphorylation regulates arrestin-mediated GPCR internalization.
Analyses of transposable elements in arbuscular mycorrhizal fungi support evolutionary parallels with filamentous plant pathogens
Authors: Oliveira Jordana I. N. , Lane Catrina , Mugambi Ken , Yildirir Gokalp , Nicol Ariane M. , Kokkoris Vasilis , Banchini Claudia , Dadej Kasia , Dettman Jeremy , Stefani Franck , Corradi Nicolas
Published: November 2024

Transposable elements (TEs) are repetitive DNA sequences that excise or create copies that are inserted elsewhere in the genome. Their expansion shapes genome variability and evolution by impacting gene expression and rearrangement rates. Arbuscular mycorrhizal fungi (AMF) are beneficial plant symbionts with large, TE-rich genomes, and recent findings showed these elements vary significantly in abundance, evolution, and regulation among model AMF strains. Here, we aimed to obtain a more comprehensive understanding of TE function and evolution in AMF by investigating assembled genomes from representatives of all known families. We uncovered multiple, family-specific bursts of insertions in different species, indicating variable past and ongoing TE activity contributing to the diversification of AMF lineages. We also found that TEs are preferentially located within and around candidate effectors/secreted proteins, as well as in proximity to promoters. Altogether, these findings support the role of TEs in promoting the diversity in proteins involved in molecular dialogues with hosts and, more generally, in driving gene regulation. The mechanisms of TEs evolution we observed in these prominent plant symbionts bear striking similarities to those of many filamentous plant pathogens.
PreciCE: Precision engineering of cell fates via data-driven multi-gene control of transcriptional networks
Authors: Magnusson Jens P. , Roohani Yusuf , Stauber Daniel , Situ Yinglin , de Castroviejo Teba Paloma Ruiz , Sandberg Rickard , Leskovec Jure , Qi Lei S.
Published: November 2024

The directed differentiation of stem cells into specific cell types is critical for regenerative medicine and cell-based applications. However, current methods for cell fate control are inefficient, imprecise, and rely on laborious trial-and-error. To address these limitations, we present a method for data-driven multi-gene modulation of transcriptional networks. We develop bidirectional CRISPR-based tools based on dCas12a, Cas13d, and dCas9 for simultaneously activating and repressing many genes. Due to the vast combinatorial complexity of multi-gene regulation, we introduce a machine learning-based computational algorithm that uses single-cell RNA sequencing data to predict multi-gene perturbation sets for converting a starting cell type into a desired target cell type. By combining these technologies, we establish a unified workflow for data-driven cell fate engineering and demonstrate its efficacy in controlling early stem cell differentiation while suppressing alternative lineages through logic-based cell fate operations. This approach represents a significant advancement in the use of synthetic biology to engineer cell identity.
Comment on “Quantum multiplication algorithm based on the convolution theorem”
Authors: Pfeffer Philipp
Published: November 2024

In their recent paper, Ramezani [] presented a quantum multiplication algorithm with O(Nlog2(N)) operations, while the best classical algorithm [Harvey and van der Hoeven, ] needs O(Nlog(N)) operations. This Comment corrects the incompleteness of the quantum complexity, showing that the classical method performs better.

Published by the American Physical Society
2024
Microscopic examination of rf-cavity-quality niobium films through local nonlinear microwave response
Authors: Wang Chung-Yang , Pereira Carlota , Leith Stewart , Rosaz Guillaume , Anlage Steven M.
Published: November 2024

The performance of superconducting radio-frequency (SRF) cavities is sometimes limited by local defects. To investigate the rf properties of these local defects, especially those that nucleate rf magnetic vortices, a near-field magnetic microwave microscope is employed. Local third-harmonic response (P3f) and its temperature dependence and rf power dependence are measured for one Nb/Cu film grown by direct current magnetron sputtering (DCMS) and six Nb/Cu films grown by high-power impulse magnetron sputtering (HiPIMS) with systematic variation of deposition conditions. Five out of the six HiPIMS Nb/Cu films show a strong third-harmonic response that is likely coming from rf vortex nucleation due to a low-Tc surface defect with a transition temperature between 6.3 and 6.8 K, suggesting that this defect is a generic feature of air-exposed HiPIMS Nb/Cu films. A phenomenological model of surface-defect grain boundaries hosting a low-Tc impurity phase is introduced and studied with time-dependent Ginzburg-Landau (TDGL) simulations of probe-sample interaction to better understand the measured third-harmonic response. The simulation results show that the third-harmonic response of rf vortex nucleation caused by surface defects exhibits the same general features as the data, including peaks in third-harmonic response with temperature, and their shift and broadening with higher microwave amplitude. We find that the parameters of the phenomenological model (the density of surface defects that nucleate rf vortices and the depth an rf vortex travels through these surface defects) vary systematically with film deposition conditions. From the point of view of these two properties, the Nb/Cu film that is most effective at reducing the nucleation of rf vortices associated with surface defects can be identified.

Published by the American Physical Society
2024
Likely existence of bound states and the Efimov effect in the triple-
J/ψ
system
Authors: Pan Ya-Wen , Liu Zhi-Wei , Geng Li-Sheng , Hosaka Atsushi , Liu Xiang
Published: November 2024

The ground-breaking discovery of the first fully charmed tetraquark state X(6900) in the J/ψJ/ψ invariant mass distribution by the LHCb collaboration has inspired intensive theoretical studies. Various interpretations, such as molecular states, compact tetraquark states, and coupled-channel effects, have been proposed for these states. Of particular interest is the ongoing search for the triple-J/ψ state–a fully-charmed hexaquark state. To deepen our understanding of the triple-J/ψ state and to guide future experimental searches, we study the triple-J/ψ system in this work employing the Gaussian expansion method and the J/ψJ/ψ potential parametrized to yield a shallow bound state, as suggested in several theoretical works. Our results support a triple-J/ψ bound state, even in cases where the attractive interaction between the two J/ψ mesons is very weak. Moreover, our analysis implies the Efimov effect in the triple-J/ψ system. In addition, we extend our investigation to the triple-ϒ(1S) system and obtain results similar to those for the triple-J/ψ system.

Published by the American Physical Society
2024
Scale setting and hadronic properties in the light quark sector with (
2+1
)-flavor Wilson fermions at the physical point
Authors: Aoyama Tatsumi , Doi Takahiro M. , Doi Takumi , Itou Etsuko , Lyu Yan , Murakami Kotaro , Sugiura Takuya ,   HAL QCD collaboration
Published: November 2024

We report scale setting and hadronic properties for our new lattice QCD gauge configuration set (HAL-conf-2023). We employ (2+1)-flavor nonperturbatively improved Wilson fermions with stout smearing and the Iwasaki gauge action on a 964 lattice, and generate configurations of 8000 trajectories at the physical point. We show the basic properties of the configurations such as the plaquette value, topological charge distribution and their autocorrelation times. The scale setting is performed by detailed analyses of the Ω baryon mass. We calculate the physical results of quark masses, decay constants of pseudoscalar mesons and single hadron spectra in light quark sector. The masses of the stable hadrons are found to agree with the experimental values within a subpercent level.

Published by the American Physical Society
2024
Stealth dark matter spectrum using Laplacian Heaviside smearing and irreducible representations
Authors: Brower R. C. , Culver C. , Cushman K. K. , Fleming G. T. , Hasenfratz A. , Howarth D. , Ingoldby J. , Jin X. Y. , Kribs G. D. , Meyer A. S. , Neil E. T. , Osborn J. C. , Owen E. , Park S. , Rebbi C. , Rinaldi E. , Schaich D. , Vranas P. , Weinberg E. , Witzel O. ,   Lattice Strong Dynamics (LSD) Collaboration
Published: November 2024

We present nonperturbative lattice calculations in the quenched approximation of the low-lying meson and baryon spectrum of the SU(4) gauge theory with fundamental fermion constituents. This theory is one instance of stealth dark matter, a class of strongly coupled theories, where the lowest mass stable baryon is the dark matter candidate. This work constitutes the first milestone in the program to study stealth dark matter self-interactions. Here, we focus on reducing excited state contamination in the single-baryon channel by applying the Laplacian Heaviside method, as well as projecting our baryon operators onto the irreducible representations of the octahedral group. We compare our resulting spectrum to previous work involving Gaussian smeared nonprojected operators and find good agreement with reduced statistical uncertainties. We also present the spectrum of the low-lying odd-parity baryons for the first time.

Published by the American Physical Society
2024