bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripartum depression symptom trajectories, telomere length and genotype, and adverse childhood experiences
Authors: Vrettou Maria , Lager Susanne , Toffoletto Simone , Iliadis Stavros I. , Kallak Theodora Kunovac , Agnafors Sara , Nieratschker Vanessa , Skalkidou Alkistis , Comasco Erika
Published: October 2024

Background

As a biological marker for cellular senescence, telomere length (TL) has been linked to a variety of psychiatric disorders and adverse childhood experiences (ACE), though only preliminarily to peripartum depression (PPD). The present study sought to examine the association between TL and PPD, assessing the moderating role of ACE and genetic polymorphic variations related with the telomere machinery.

Methods

Adversity was self-reported, likewise were depressive symptoms evaluated at pregnancy week 17 and 32, as well as six-weeks and six-months postpartum. TL was assessed by use of qPCR in blood samples collected during delivery from females with antenatal depression resolving postpartum, females with depression persisting to postpartum, and healthy controls. Twenty haplotype-tagging Single Nucleotide Polymorphisms in the Telomerase Reverse Transcriptase (TERT) and three in the Telomerase RNA Component (TERC) genes were genotyped.

Results

TL was negatively correlated with severity of PPD symptoms at pregnancy week 32 and postpartum week 6. PPD was associated with shorter TL. Lastly, ACE, but not the TERT/TERC genotype, moderated the TL-trajectory association; with increasing ACE, individuals with persistent PPD symptoms had shorter TL, whereas the opposite pattern (longer TL) was observed in the controls.

Conclusions

The findings contribute to further understanding of PPD underpinnings, suggesting a negative relationship with TL.
Moving towards transformative justice for black women survivors of intimate partner violence: an intersectional qualitative study
Authors: Sharpless Laurel , Kershaw Trace , Knight Deja , Campbell Julia K. , Phillips Karlye , Katague Marina , Willie Tiara C.
Published: October 2024

Background

Intimate partner violence (IPV) disproportionately affects Black women, yet the current IPV justice response, relying on the criminal legal system, often fails them due to racialized, sexist stereotypes that disrupt Black women’s claims to survivorship. Transformative justice, a community-based approach designed to repair harm between the survivor and person who caused harm and transform the social conditions that perpetuate violence, may be a promising alternative approach to facilitate justice and accountability for IPV. However, little is known about the justice preferences of Black women IPV survivors. This qualitative study sought to understand Black women IPV survivors’ experiences interacting with police and their justice preferences following IPV.

Methods

Semi-structured interviews with 15 Black women IPV survivors were conducted between April 2020 and April 2022. Inductive analytic techniques derived from grounded theory were used to contextualize Black women IPV survivors’ experiences.

Results

One theme was identified that aligned with Black women IPV survivors’ experiences interacting with the police: 1) fear and distrust. Four themes were identified that aligned with justice preferences: (1) resolution through dialogue, (2) therapy and counseling services, (3) resource support, and (4) protection and prevention for children. Fear and distrust of the police was mainly driven by anticipated discrimination. Survivors’ justice preferences encompassed solution-based dialogue between the survivor and person who caused harm mediated by family and trusted individuals in the community, therapy services, housing support, and attention to preventing the intergenerational cycle of IPV for children as part of a community-based, holistic justice response.

Conclusions

Police interactions as part of the current justice response were counterproductive for Black women IPV survivors. Black women IPV survivors deserve alternative forms of justice and accountability for IPV. As an alternative justice response to IPV, transformative justice can encompass their justice preferences and promote equity and center Black women IPV survivors and their communities.
Development and validation of the Thai Halitosis Associated Life-Quality Test (T-HALT): an evaluation of psychometric properties
Authors: Satravaha Yodhathai , Thitiwatpalakarn Katkarn , Peanchitlertkajorn Supakit , Boonpratham Supatchai , Chaweewannakorn Chaiyapol , Sipiyaruk Kawin
Published: October 2024

Background

Halitosis appears to have significant impacts on quality of life, necessitating reliable assessment tools. The Halitosis Associated Life-Quality Test (HALT) has been validated in various populations, but not among Thai people. While HALT provides a valuable foundation, there is a need for a culturally adapted and expanded instrument for the Thai context. Consequently, this study aimed to develop and validate a comprehensive questionnaire for assessing halitosis-related quality of life in Thai populations, incorporating a Thai version of HALT (T-HALT) as a core component.

Materials and methods

This cross-sectional study involved 200 dental patients at Mahidol University. The original HALT was translated into Thai using forward-backward translation. Cultural adaptation and psychometric properties of T-HALT were evaluated through multiple approaches. Content validity was ensured through expert reviews, while face validity was assessed by patient feedback. Reliability was examined via test-retest and internal consistency measures. Criterion and discriminant validity was evaluated by correlating T-HALT scores with self-perceived halitosis and volatile sulfur compound (VSC) measurements, respectively. VSCs were quantified using the OralChroma™ device, which analyzes breath samples collected directly from patients’ mouths. Construct validity was assessed through exploratory (EFA) and confirmatory factor analysis (CFA), providing insights into the questionnaire’s underlying structure.

Results

T-HALT demonstrated excellent internal consistency (Cronbach’s alphas = 0.940–0.943) and test-retest reliability (ICC = 0.886). Criterion validity was supported by a significant correlation between T-HALT scores and self-perceived halitosis (r = 0.503, P < 0.001). Discriminant validity was confirmed by the absence of a significant correlation between T-HALT scores and VSC levels (r = 0.071, P = 0.32). EFA revealed a four-factor structure, which was subsequently confirmed by CFA. However, Items 1 and 7 were excluded due to poor standardized factor loadings.

Conclusion

T-HALT demonstrates good reliability and validity for assessing halitosis-related quality of life in Thai populations. It performs well as a unidimensional measure, but its multidimensional application requires modifications. Future research should validate a modified version excluding Items 1 and 7 across diverse Thai populations, potentially enhancing its cultural specificity.
Narratives of resilience: Understanding Iranian breast cancer survivors through health belief model and stress-coping theory for enhanced interventions
Authors: Mehrabizadeh Mohaddese , Zaremohzzabieh Zeinab , Zarean Mansoureh , Ahrari Seyedali , Ahmadi Ali-Reza
Published: October 2024

Breast cancer poses a significant global health challenge, with Iran experiencing particularly high incidence and mortality rates. Understanding the adaptation process of Iranian breast cancer survivors’ post-treatment is crucial. This study explores the health perceptions, barriers, and coping mechanisms of Iranian survivors by integrating Stress-Coping Theory (SCT) and the Health Belief Model (HBM). Semi-structured interviews were conducted with 17 survivors, and a grounded theory approach guided the deductive content analysis of the data. The findings reveal key themes, including perceived susceptibility, benefits, barriers to care, cues to action, self-efficacy, and appraisal of action. Perceived susceptibility highlights diagnostic challenges stemming from practitioner errors and symptom misconceptions. Perceived benefits underscore the importance of early detection and support from healthcare providers and families. Barriers include cultural and financial obstacles, while cues to action reflect the influence of media, family, and personal experiences on healthcare-seeking behavior. The study also examines coping strategies, such as problem-focused and emotion-focused approaches, along with family support and external stressors. To address these barriers and enhance support systems, the study suggests specific strategies for healthcare providers, including targeted training to improve diagnostic accuracy and patient communication. Culturally sensitive awareness campaigns can correct symptom misconceptions, while financial counseling can mitigate economic barriers. Establishing community-based support groups and involving family members in care plans can enhance emotional and psychological support. These strategies aim to overcome the identified barriers and improve support systems for Iranian breast cancer survivors, ultimately fostering better recovery outcomes.
Clinicians’ use of Health Information Exchange technologies for medication reconciliation in the U.S. Department of Veterans Affairs: a qualitative analysis
Authors: Snyder Margie E. , Nguyen Khoa A. , Patel Himalaya , Sanchez Steven L. , Traylor Morgan , Robinson Michelle J. , Damush Teresa M. , Taber Peter , Mixon Amanda S. , Fan Vincent S. , Savoy April , Dismore Rachel A. , Porter Brian W. , Boockvar Kenneth S. , Haggstrom David A. , Locke Emily R. , Gibson Bryan S. , Byerly Susan H. , Weiner Michael , Russ-Jara Alissa L.
Published: October 2024

Background

Medication reconciliation is essential for optimizing medication use. In part to promote effective medication reconciliation, the Department of Veterans Affairs (VA) invested substantial resources in health information exchange (HIE) technologies. The objectives of this qualitative study were to characterize VA clinicians’ use of HIE tools for medication reconciliation in their clinical practice and to identify facilitators and barriers.

Methods

We recruited inpatient and outpatient prescribers (physicians, nurse practitioners, physician assistants) and pharmacists at four geographically distinct VA medical centers for observations and interviews. Participants were observed as they interacted with HIE or medication reconciliation tools during routine work. Participants were interviewed about clinical decision-making pertaining to medication reconciliation and use of HIE tools, and about barriers and facilitators to use of the tools. Qualitative data were analyzed via inductive and deductive approaches using a priori codes.

Results

A total of 63 clinicians participated. Over half (58%) were female, and the mean duration of VA clinical experience was 7 (range 0–32) years. Underlying motivators for clinicians seeking data external to their VA medical center were having new patients, current patients receiving care from an external institution, and clinicians’ concerns about possible medication discrepancies among institutions. Facilitators for using HIE software were clinicians’ familiarity with the HIE software, clinicians’ belief that medication information would be available within HIE, and their confidence in the ability to find HIE medication-related data of interest quickly. Six overarching barriers to HIE software use for medication coordination included visual clutter and information overload within the HIE display; challenges with HIE interface navigation; lack of integration between HIE and other electronic health record interfaces, necessitating multiple logins and application switching; concerns with the dependability of HIE medication information; unfamiliarity with HIE tools; and a lack of HIE data from non-VA facilities.

Conclusions

This study is believed to be the first to qualitatively characterize clinicians’ HIE use with respect to medication reconciliation. Results inform recommendations to optimize HIE use for medication management activities. We expect that healthcare organizations and software vendors will be able to apply the findings to develop more effective and usable HIE information displays.
Time-varying exposure to food retailers and cardiovascular disease hospitalization and mortality in the netherlands: a nationwide prospective cohort study
Authors: Pinho Maria Gabriela M. , Koop Yvonne , Mackenbach Joreintje D. , Lakerveld Jeroen , Simões Mariana , Vermeulen Roel , Wagtendonk Alfred J. , Vaartjes Ilonca , Beulens Joline W. J.
Published: October 2024

Background

Very few studies to date investigated the prospective association of changes in exposure to the food environment with cardiovascular disease (CVD) risk. We aim to explore if time-varying exposure to the food environment was associated with hospitalization and mortality due to total and specific types of CVD in The Netherlands.

Methods

In this prospective cohort study, 4,641,435 Dutch adults aged 35 + years who did not change residence in 2002–2018 were identified through registry data. Exposure to the food environment was defined as time-varying Food Environment Healthiness Index (FEHI) scores (range: − 5 to 5) and time-varying kernel density of specific food retailers (e.g., fast food outlets, supermarkets) around the home location between 2004 and 2018. The main outcome measures were hospitalization and mortality due to overall CVD, stroke, HF, and CHD occurring between 2004 and 2020, based on hospital and death registries.

Results

In Cox regression models, each unit increase in the FEHI was associated with a lower hospitalization and mortality of CVD (hospitalization hazard ratio (HRh) = 0.90 (0.89 to 0.91), mortality hazard ratio (HRm) = 0.85 (0.82 to 0.89)), CHD (HRh = 0.88 (0.85 to 0.91), HRm = 0.80 (0.75 to 0.86)), stroke (HRh = 0.89 (0.84 to 0.93)), HRm = 0.89 (0.82 to 0.98)), and HF (HRh = 0.90 (0.84–0.96), HRm = 0.84 (0.76 to 0.92)). Increased density of local food shops, fast food outlets, supermarkets, and convenience stores and decreased density of food delivery outlets and restaurants were associated with a higher risk of CVD, CHD, stroke, and HF hospitalization and mortality.

Conclusions

In this observational longitudinal study, changes in exposure to a healthier food environment over 14 years were associated with a risk reduction in CVD hospitalization and mortality, in particular in urbanized areas and for younger adults and those with higher incomes.
SSRI use during acute COVID-19 and risk of Long COVID among patients with depression
Authors: Butzin-Dozier Zachary , Ji Yunwen , Deshpande Sarang , Hurwitz Eric , Anzalone A. Jerrod , Coyle Jeremy , Shi Junming , Mertens Andrew , van der Laan Mark J. , Colford John M. , Patel Rena C. , Hubbard Alan E. ,   the National COVID Cohort Collaborative (N3C) Consortium
Published: October 2024

Background

Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication.

Methods

In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates.

Results

We analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)).

Conclusions

These findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.
Oral administration of Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 ameliorates DSS-induced colitis in mice
Authors: Zhang Manqi , Xu Xichao , Su Liqian , Zeng Yuqing , Lin Jingxiong , Li Wenwen , Zou Yigui , Li Sicong , Lin Boxian , Li Ziyuan , Chen Hu , Huang Yuheng , Xu Quanle , Chen Hongbo , Cheng Fang , Dai Dongling
Published: October 2024

Ulcerative colitis (UC) belongs to chronic inflammatory disease with a relapsing characterization. Conventional oral drugs of UC are restricted in clinical by premature degradation in the gastrointestinal tract, modest efficacy, and adverse effects. CX5461 can treat autoimmune disease, immunological rejection, and vascular inflammation. However, low solubility, intravenous administration, and non-inflammatory targeting limited its clinical application. Herein, this work aims to develop Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 (SFELNVs@CX5461) for efficient CX5461 oral delivery for UC therapy. We identified SFELNVs as nano-diameter (80 nm) with negative zeta potential (-32mV). Cellular uptake has shown that SFELNVs were targeted uptake by macrophages, thus increasing drug concentration. Additionally, oral SFELNVs@CX5461 exhibited good safety and stability, as well as inflammation-targeting ability in the gastrointestinal tract of dextran sodium sulfate (DSS)-induced colitis mice. In vivo, oral administration of SFELNVs and CX5461 could relieve mice colitis. More importantly, combined SFELNVs and CX5461 alleviated mice colitis by inhibiting pro-inflammatory factors (TNF-α, IL-1β, and IL-6) expression and promoting M2 macrophage polarization. Furthermore, SFELNVs promoted M2 polarization by miR4371c using miRNA sequencing. Our results suggest that SFELNVs@CX5461 represents a novel orally therapeutic drug that can ameliorate colitis, and a promising targeting strategy for safe UC therapy.
Use of a newly developed minimally invasive bilateral fixed angle locking system in the treatment of pathological pelvic fractures: a case series
Authors: Unthan Mark , Marintschev Ivan , Spiegel Christian , Hofmann Gunther O. , Weschenfelder Wolfram
Published: October 2024

Background

Metastatic bone disease (MBD) and its complications have a significant impact on patients’ quality of life. Pathological fractures are a particular problem as they affect patient mobility and pose a high risk of non-union. The pelvis is frequently affected by MBD and its fixation is challenging. We present a case series of three pathological sacral fractures treated with a new minimally invasive bilateral fixed angle locking system.

Case presentation

Case 1 and 2 suffered a pathological transforaminal sacral fracture without adequate trauma in stage 4 carcinomas (gastric cancer and breast cancer). Both were initially treated with non-surgical treatment, which had only a limited effect and led to imminent immobility. Both were operated on with fluoroscopic navigation and underwent transsacral SACRONAIL® stabilisation according to CT morphology (S1 + S2 and S1 respectively). Immediately after the operation, pain decreased and mobilisation improved. Case 3 had a pathological transalar sacral fracture during the 2nd cycle of chemotherapy due to non-Hodgkin’s lymphoma. He soon became immobile and could only move in a wheelchair. The operation was performed with CT navigation due to the very small corridors and an implant was inserted in S1 and S2. The patient reported immediate pain relief and his ability to walk improved over the following months. Despite continued chemotherapy, no wound complications occurred.

Conclusions

The cases show the advantages of the minimally invasive bilateral fixed angle locking system SACRONAIL® in the treatment of patients with pathological sacral fractures. It allows immediate full weight bearing and the risk of secondary surgical complications is low. All cases showed an improvement in pain scores and mobility.
Molecular quantification of fritillariae cirrhosae bulbus and its adulterants
Authors: Liu Ziyi , Pei Yifei , Chen Tiezhu , Yang Zemin , Jiang Wenjun , Feng Xue , Li Xiwen
Published: October 2024

Background

Fritillariae Cirrhosae Bulbus (FCB) is frequently adulterated with its closely related species due to personal or non-man made factors, leading to alterations in the composition of its constituents and compromising the efficacy of its products.

Methods

The specific single nucleotide polymorphisms (SNPs) were screened by comparing candidate barcodes of Fritillaria and verified by amplification and sequencing. Herb molecular quantification (Herb-Q) was established by detecting specific SNPs, and the methodological validation was performed. Quantitative standard curves were established for FCB mixed with each adulterated species, and the quantitative validity of this method was verified based on external standard substance. In addition, eight commercial Shedan Chuanbei capsules (SDCBs) randomly selected were detected.

Results

FCB and its five adulterants can be distinguished based on the ITS 341 site. The methodological investigation of Herb-Q shows optimal accuracy, and repeatability, which exhibited good linearity with an R2 of 0.9997 (> 0.99). An average bias in quantitative validity was 5.973% between the measured and actual values. Four of eight commercial SDCBs were adulterated with F. ussuriensis or F. thunbergia with adulteration levels ranging from 9 to 15% of the total weight.

Conclusion

This study confirmed that Herb-Q can quantitatively detect both the mixed herbs and Chinese patent medicines (CPMs) containing FCB with high reproducibility and accuracy. This method provides technical support for market regulation and helps safeguard patient rights.
Integrating deep phenotyping with genetic analysis: a comprehensive workflow for diagnosis and management of rare bone diseases
Authors: Li Guozhuang , Xu Kexin , Yin Xiangjie , Yang Jianle , Cai Jihao , Yang Xinyu , Li Qing , Wang Jie , Zhao Zhengye , Mahesahti Aoran , Zhang Ning , Zhang Terry Jianguo , Wu Nan
Published: October 2024

Phenotypes play a fundamental role in medical genetics, serving as external manifestations of underlying genotypes. Deep phenotyping, a cornerstone of precision medicine, involves precise multi-system phenotype assessments, facilitating disease subtyping and genetic understanding. Despite their significance, the field lacks standardized protocols for accurate phenotype evaluation, hindering clinical comprehension and research comparability. We present a comprehensive workflow of deep phenotyping for rare bone diseases from the Genetics Clinic of Skeletal Deformity at Peking Union Medical College Hospital. Our workflow integrates referral, informed consent, and detailed phenotype evaluation through HPO standards, capturing nuanced phenotypic characteristics using clinical examinations, questionnaires, and multimedia documentation. Genetic testing and counseling follow, based on deep phenotyping results, ensuring personalized interventions. Multidisciplinary team consultations facilitate comprehensive patient care and clinical guideline development. Regular follow-up visits emphasize dynamic phenotype reassessment, ensuring treatment strategies remain responsive to evolving patient needs. In conclusion, this study highlights the importance of deep phenotyping in rare bone diseases, offering a standardized framework for phenotype evaluation, genetic analysis, and multidisciplinary intervention. By enhancing clinical care and research outcomes, this approach contributes to the advancement of precision medicine in the field of medical genetics.
Current advances and challenges in Managing Hereditary Diffuse Gastric Cancer (HDGC): a narrative review
Authors: van der Sluis L. , van Dieren J.M. , van der Post R.S. , Bisseling T.M.
Published: October 2024

More than 25 years ago, CDH1 pathogenic variants (PVs) were identified as the primary cause of hereditary diffuse gastric cancer (HDGC), an inherited cancer syndrome that increases the lifetime risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC). Since DGC is associated with a poor prognosis, a prophylactic total gastrectomy (PTG) is currently the gold standard for reducing the risk of DGC in CDH1 PV carriers. However, as germline genetic testing becomes more widespread, many CDH1 PV carriers have been identified, including in families with lower penetrance levels or without a history of gastric cancer (GC). When including these families, recent findings suggest that the cumulative lifetime risk of developing advanced DGC is much lower than previously thought and is now estimated to be 13–19%. This lower risk, combined with the fact that around one third of the CDH1 PV carriers decline PTG due to potential lifelong physical and psychological consequences, raises critical questions about the current uniformity in recommending PTG to all CDH1 PV carriers. As a result, there is a growing need to consider alternative strategies, such as endoscopic surveillance. However, despite the currently lower estimated risk of infiltrative (advanced) DGC, almost every PTG specimen shows the presence of small low-stage (pT1a) signet ring cell (SRC) lesions of which the behaviour is unpredictable but often are considered indolent or premalignant stages of DGC. Therefore, the primary goal of surveillance should be to identify atypical, deeper infiltrating lesions rather than every SRC lesion. Understanding the progression from indolent to more infiltrative lesions, and recognizing their endoscopic and histological features, is crucial in deciding the most suitable management option for each individual.
Blood trauma in veno-venous extracorporeal membrane oxygenation: low pump pressures and low circuit resistance matter
Authors: Blum Christopher , Landoll Micha , Strassmann Stephan E. , Steinseifer Ulrich , Neidlin Michael , Karagiannidis Christian
Published: October 2024

Background

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become standard of care in patients with the most severe forms of acute respiratory distress syndrome. However, hemolysis and bleeding are one of the most frequent side effects, affecting mortality. Despite the widespread use of VV ECMO, current protocols lack detailed, in-vivo data-based recommendations for safe ECMO pump operating conditions. This study aims to comprehensively analyze the impact of VV ECMO pump operating conditions on hemolysis by combining in-silico modeling and clinical data analysis.

Methods

We combined data from 580 patients treated with VV ECMO in conjunction with numerical predictions of hemolysis using computational fluid dynamics and reduced order modeling of the Rotaflow (Getinge) and DP3 (Xenios) pumps. Blood trauma parameters across 94,779 pump operating points were associated with numerical predictions of shear induced hemolysis.

Results

Minimal hemolysis was observed at low pump pressures and low circuit resistance across all flow rates, whereas high pump pressures and circuit resistance consistently precipitated substantial hemolysis, irrespective of flow rate. However, the lower the flow rate, the more pronounced the influence of circuit resistance on hemolysis became. Numerical models validated against clinical data demonstrated a strong association (Spearman’s r = 0.8) between simulated and observed hemolysis, irrespective of the pump type.

Conclusions

Integrating in-silico predictions with clinical data provided a novel approach in understanding and potentially reducing blood trauma in VV ECMO. This study further demonstrated that a key factor in lowering side effects of ECMO support is the maintenance of low circuit resistance, including oxygenators with the lowest possible resistance, the shortest feasible circuit tubing, and cannulae with an optimal diameter.
Integration of long-read sequencing, DNA methylation and gene expression reveals heterogeneity in Y chromosome segment lengths in phenotypic males with 46,XX testicular disorder/difference of sex development
Authors: Berglund Agnethe , Johannsen Emma B. , Skakkebæk Anne , Chang Simon , Rohayem Julia , Laurentino Sandra , Hørlyck Arne , Drue Simon O. , Bak Ebbe Norskov , Fedder Jens , Tüttelmann Frank , Gromoll Jörg , Just Jesper , Gravholt Claus H.
Published: October 2024

Background

46,XX testicular disorder/difference of sex development (46,XX DSD) is a rare congenital condition, characterized by a combination of the typical female sex chromosome constitution, 46,XX, and a variable male phenotype. In the majority of individuals with 46,XX DSD, a Y chromosome segment containing the sex-determining region gene (SRY) has been translocated to the paternal X chromosome. However, the precise genomic content of the translocated segment and the genome-wide effects remain elusive.

Methods

We performed long-read DNA sequencing, RNA sequencing and DNA methylation analyses on blood samples from 46,XX DSD (n = 11), male controls (46,XY; variable cohort sizes) and female controls (46,XX; variable cohort sizes), in addition to RNA sequencing and DNA methylation analysis on blood samples from males with Klinefelter syndrome (47,XXY, n = 22). We also performed clinical measurements on all 46,XX DSD and a subset of 46,XY (n = 10).

Results

We identified variation in the translocated Y chromosome segments, enabling subcategorization into 46,XX DSD (1) lacking Y chromosome material (n = 1), (2) with short Yp arms (breakpoint at 2.7–2.8 Mb, n = 2), (3) with medium Yp arms (breakpoint at 7.3 Mb, n = 1), and (4) with long Yp arms (n = 7), including deletions of AMELY, TBLY1 and in some cases PRKY. We also identified variable expression of the X-Y homologues PRKY and PRKX. The Y-chromosomal transcriptome and methylome reflected the Y chromosome segment lengths, while changes to autosomal and X-chromosomal regions indicated global effects. Furthermore, transcriptional changes tentatively correlated with phenotypic traits of 46,XX DSD, including reduced height, lean mass and testicular size.

Conclusion

This study refines our understanding of the genetic composition in 46,XX DSD, describing the translocated Y chromosome segment in more detail than previously and linking variability herein to genome-wide changes in the transcriptome and methylome.
Strengthening crisis resilience in German primary care by using quality indicators: findings of a process evaluation in the RESILARE project
Authors: Poß-Doering Regina , Koetsenruijter Jan , Litke Nicola Alexandra , Weis Aline , Köppen Martina , Kümmel Stephanie , Szecsenyi Joachim , Wensing Michel
Published: October 2024

Background

In recent years, health systems worldwide have been confronted with several crises such as natural disasters or the COVID-19 pandemic, that affected lives and health of many people. In light of waves of infections and heat, climate change is considered to be the biggest health threat of the 21st century. Strengthening individual and organizational crisis resilience in healthcare settings thus becomes a crucial factor in maintaining care quality and protecting vulnerable patients during such crises. The RESILARE project therefore aimed to develop and evaluate quality indicators that support primary care practices in preparing for and adapting to crisis-related challenges.

Methods

In a three-phased process, indicator development was based on systematic literature research and qualitative data, a two-stage expert panel process, and pilot testing in a maximum of n = 35 ambulatory practices during an outreach visit. Practice-individual indicator-related status and benchmarking information were provided via feedback reports to complete the audit and feedback program. A mixed-methods process evaluation used semistructured interviews with participating General practitioners and nonphysician health professionals to explore support and challenges for the implementation of the derived set of quality indicators. Two online surveys were conducted to evaluate all indicators and the two-part feedback report. Qualitative data were analyzed inductively using a thematic analysis approach. Survey data were analyzed descriptively.

Results

A total of n = 32 indicators covered four domains: (1) individual resilience, (2) crisis prevention, (3) organizational resilience, and (4) climate resilience. N = 34 practices participated in the piloting and the process evaluation. Participants generally attributed a high relevance to the domains, and considered the indicator set suitable for implementation into existing quality management systems. Planning and implementation of measures that strengthen crisis resilience in practices were triggered or intensified by piloting the indicators and by the two-part feedback report. The identified challenges involved the volume of indicators and practice-individual implementation of renewable energy sources on rented premises. Participants expressed their desire for peer exchange regarding proven concepts for crisis resilience.
Unraveling the role of long non-coding RNAs in chronic heat stress-induced muscle injury in broilers
Authors: Liu Zhen , Liu Yingsen , Xing Tong , Li Jiaolong , Zhang Lin , Zhao Liang , Jiang Yun , Gao Feng
Published: October 2024

Background

Chronic heat stress (CHS) is a detrimental environmental stressor with a negative impact on the meat quality of broilers. However, the underlying mechanisms are not fully understood. This study investigates the effects of CHS on long non-coding RNA (lncRNA) expression and muscle injury in broilers, with a focus on its implications for meat quality.

Results

The results showed that CHS diminished breast muscle yield, elevated abdominal fat deposition, induced cellular apoptosis (P < 0.05), and caused myofibrosis. Transcriptomic analysis revealed 151 differentially expressed (DE) lncRNAs when comparing the normal control (NC) and HS groups, 214 DE lncRNAs when comparing the HS and PF groups, and 79 DE lncRNAs when comparing the NC and pair-fed (PF) groups. After eliminating the confounding effect of feed intake, 68 lncRNAs were identified, primarily associated with cellular growth and death, signal transduction, and metabolic regulation. Notably, the apoptosis-related pathway P53, lysosomes, and the fibrosis-related gene TGF-β2 were significantly upregulated by lncRNAs.

Conclusions

These findings indicate that chronic heat stress induces cellular apoptosis and muscle injury through lncRNA, leading to connective tissue accumulation, which likely contributes to reduced breast muscle yield and meat quality in broilers.
Leveraging large-scale datasets and single cell omics data to develop a polygenic score for cisplatin-induced ototoxicity
Authors: Miao Deanne Nixie R. , Wilke MacKenzie A. P. , Pham John , Ladha Feryal , Singh Mansumeet , Arsenio Janilyn , Luca Emilia , Dabdoub Alain , Yang Wejian , Yang Jun J. , Drögemöller Britt I.
Published: October 2024

Background

Cisplatin-induced ototoxicity (CIO), characterized by irreversible and progressive bilateral hearing loss, is a prevalent adverse effect of cisplatin chemotherapy. Alongside clinical risk factors, genetic variants contribute to CIO and genome-wide association studies (GWAS) have highlighted the polygenicity of this adverse drug reaction. Polygenic scores (PGS), which integrate information from multiple genetic variants across the genome, offer a promising tool for the identification of individuals who are at higher risk for CIO. Integrating large-scale hearing loss GWAS data with single cell omics data holds potential to overcome limitations related to small sample sizes associated with CIO studies, enabling the creation of PGSs to predict CIO risk.

Results

We utilized a large-scale hearing loss GWAS and murine inner ear single nuclei RNA-sequencing (snRNA-seq) data to develop two polygenic scores: a hearing loss PGS (PGSHL) and a biologically informed PGS for CIO (PGSCIO). The PGSCIO included only variants which mapped to genes that were differentially expressed within cochlear cells that showed differential abundance in the murine snRNA-seq data post-cisplatin treatment. Evaluation of the association of these PGSs with CIO in our target CIO cohort revealed that PGSCIO demonstrated superior performance (P = 5.54 × 10− 5) relative to PGSHL (P = 2.93 × 10− 3). PGSCIO was also associated with CIO in our test cohort (P = 0.04), while the PGSHL did not show a significant association with CIO (P = 0.52).

Conclusion

This study developed the first PGS for CIO using a large-scale hearing loss dataset and a biologically informed filter generated from cisplatin-treated murine inner ear snRNA-seq data. This innovative approach offers new avenues for developing PGSs for pharmacogenomic traits, which could contribute to the implementation of tailored therapeutic interventions. Further, our approach facilitated the identification of specific cochlear cells that may play critical roles in CIO. These novel insights will guide future research aimed at developing targeted therapeutic strategies to prevent CIO.
Coverage of community-wide mass drug administration platforms for soil-transmitted helminths in Benin, India, and Malawi: findings from the DeWorm3 project
Authors: Means Arianna Rubin , Ásbjörnsdóttir Kristjana Hrönn , Sharrock Katherine C. , Galagan Sean R. , Aruldas Kumudha , Avokpaho Euripide , Chabi Félicien , Halliday Katherine E. , Houngbegnon Parfait , Israel Gideon John , Kaliappan Saravanakumar Puthupalayam , Kennedy David , Legge Hugo , Oswald William E. , Palanisamy Gokila , Rogers Elliott , Timothy Joseph , Pearman Emily , Ramesh Rohan Michael , Simwanza James , Sheik-Abdullah Jasmine Farzana , Sheikh Mariyam , Togbevi Comlanvi Innocent , Witek-McManus Stefan , Pullan Rachel L. , Bailey Robin , Kalua Khumbo , Ibikounlé Moudachirou , Luty Adrian J. F. , Ajjampur Sitara S. R. , Walson Judd L.
Published: October 2024

Background

Soil-transmitted helminths (STH) affect approximately 1.5 billion people globally. The current STH control strategy is annual or twice-annual preventive chemotherapy, typically school-based deworming targeting children and women of reproductive age. Mathematical modeling suggests that it may be possible to interrupt STH transmission through high-coverage community-wide mass drug administration (cMDA). DeWorm3 is a cluster randomized trial testing cMDA for prevalence reduction and transmission interruption. The purpose of this study is to describe coverage of cMDA in study clusters over time and correlates of coverage at individual and cluster levels.

Methods

From 2018–2020, DeWorm3 delivered six rounds of cMDA with 400 mg albendazole at sites in Benin, India, and Malawi. We report coverage, treatment uptake, and directly observed therapy across all rounds. Factors associated with coverage at the cluster level were identified using binomial generalized estimating equations, while factors associated with non-treatment at the individual level were identified using binomial mixed-effects models.

Results

Coverage was high across all clusters and rounds, exceeding the WHO target of 75% in all sites and across all rounds (78% to 95%); cluster-level coverage tended to increase over time. Younger, unmarried, and migratory adults were more likely to be untreated at all sites; adult males were more likely to be untreated in Benin and Malawi. Among children, girls were more likely to be untreated, as were non-school-attending and migratory children. Higher adult education was associated with greater odds of non-treatment among adults, but lower odds among children in the household. Belonging to a less wealthy or minority language-speaking household was associated with non-treatment among both adults and children.

Conclusions

It is possible to deliver community-wide MDA with high coverage. Unique individual and community-level factors influence treatment across settings, and these may be addressed through targeted programming.

Trial Registration: Field Studies on the Feasibility of Interrupting the Transmission of Soil-transmitted Helminths (STH), NCT03014167.
Monte Carlo simulations of cefepime in children receiving continuous kidney replacement therapy support continuous infusions for target attainment
Authors: Hambrick H. Rhodes , Punt Nieko , Pavia Kathryn , Mizuno Tomoyuki , Goldstein Stuart L. , Tang Girdwood Sonya
Published: October 2024

Background

Sepsis is a leading cause of acute kidney injury requiring continuous kidney replacement therapy (CKRT) and CKRT can alter drug pharmacokinetics (PK). Cefepime is used commonly in critically ill children and is cleared by CKRT, yet data regarding cefepime PK and pharmacodynamic (PD) target attainment in children receiving CKRT are scarce, so we performed Monte Carlo simulations (MCS) of cefepime dosing strategies in children receiving CKRT.

Methods

We developed a CKRT “module” in the precision dosing software Edsim++. The module was added into a pediatric cefepime PK model. 1000-fold MCS were performed using six dosing strategies in patients aged 2–25 years and ≥ 10 kg with differing residual kidney function (estimated glomerular filtration rate of 5 vs 30 mL/min/1.73 m2), CKRT prescriptions, (standard-dose total effluent flow of 2500 mL/h/1.73 m2 vs high-dose of 8000 mL/h/1.73 m2), and fluid accumulation (0–30%). Probability of target attainment (PTA) was defined by percentage of patients with free concentrations exceeding bacterial minimum inhibitory concentration (MIC) for 100% of the dosing interval (100% fT > 1xMIC) and 4xMIC using an MIC of 8 mg/L for Pseudomonas aeruginosa.

Results

Assuming standard-dose dialysis and minimal kidney function, > 90% PTA was achieved for 100% fT > 1x MIC with continuous infusions (CI) of 100–150 mg/kg/day (max 4/6 g) and 4-h infusions of 50 mg/kg (max 2 g), but > 90% PTA for 100% fT > 4x MIC was only achieved by 150 mg/kg CI. Decreased PTA was seen with less frequent dosing, shorter infusions, higher-dose CKRT, and higher residual kidney function.

Conclusions

Our new CKRT-module was successfully added to an existing cefepime PK model for MCS in young patients on CKRT. When targeting 100% fT > 4xMIC or using higher-dose CKRT, CI would allow for higher PTA than intermittent dosing.
A combination of calcium hydroxide and sodium hydrosulphate controls pathogens causing environmental mastitis in recycled manure solids
Authors: Praveen Selladurai , Kataktalware Mukund A. , Meena Priyanka , Lavanya Maharajan , Patoliya Priyanka , Jeyakumar Sakthivel , Ravindra Menon Rekha , Chauhan Mamta , Ramesha K. P. , Devi G. Letha , Kastelic John P. , Dhali Arindam
Published: October 2024

Recycled manure solids (RMS) are dried cow dung processed using a manure dewatering machine and subsequently sun-dried to ~ 20% moisture. Benefits of RMS include abundant availability, low cost, and eco-friendliness, but its use as bedding material for cows is hindered by a moisture content that promotes microbial growth. This in vitro study evaluated impacts of calcium hydroxide (CH; 5 and 7.5%) and sodium hydrosulphate (SHS; 6 and 8%), independently and in combinations, at various depths of RMS, on physicochemical and microbial properties. The CH-treated groups had increased pH and reduced moisture on Day 0. Incorporating 7.5% CH + 6% SHS at 15–20 cm, and 7.5% CH + 8% SHS at all depths, effectively suppressed Escherichia coli and Klebsiella spp. Furthermore, a combination of 7.5% CH + 8% SHS at 20 cm inhibited coliform growth, whereas 7.5% CH with 6% SHS inhibited Streptococcus spp. In conclusion, a combination of 7.5% CH with either 6 or 8% SHS at a depth of 15 cm in RMS was particularly effective in controlling environmental mastitis-causing pathogens, specifically E. coli and Klebsiella spp.

Graphical Abstract
Analysis and monitoring of the behavior of a rock fill dam ten years after construction: a case study of the Iran-Madani Dam
Authors: Farajniya Rasoul , Poursorkhabi Ramin Vafaei , Zarean Ahmad , Dabiri Rouzbeh
Published: October 2024

In this study we compared dam monitoring results with those of numerical analysis to propose a plan for the first reservoir impounding of the Iran-Madani Rock fill dam, ten years after the completion of its construction. The stability of the dam body has been assessed using numerical analysis and data obtained from sensors installed in the dam. The correctness and accuracy of the geotechnical parameters of the dam body materials were confirmed by comparing the results of numerical analysis and monitoring through back analysis. The linear correlation coefficients between the experimental data and the numerical results for settlement, pore water pressure, and total stress are 84%, 67%, and 99%, respectively. In addition, the agreement between the design assumptions with both the numerical analysis results and instrumentation data was examined. The arching ratio values obtained from instrumentation and numerical analysis in the core of the dam are 0.47 and 0.35, respectively, indicating the safety of the dam. Finally, a numerical sensitivity analysis was conducted to present a special impounding program for the dam, with a focus on controlling simultaneous changes in pore water pressure and effective stress in the clay core, ten years after the completion of the dam body construction.