bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular Matrix Instability and Chronic Inflammation Underlie Maladaptive Right Ventricular Pressure Overload Remodeling and Failure in Male Mice
Authors: Russo Ilaria , Dun Wen , Mehta Swasti , Ahmed Sowda , Tzimas Christos , Fukuma Nobuaki , Tsai Emily J. 
Published: April 2024

ABSTRACTBackgroundRight ventricular dysfunction (RVD) portends increased death risk for heart failure (HF) and pulmonary arterial hypertension (PAH) patients, regardless of left ventricular function or etiology. In both, RVD arises from the chronic RV pressure overload, and represents advanced cardiopulmonary disease. RV remodeling responses and survival rates of HF and PAH patients, however, differ by sex. Men develop more severe RVD and die at younger ages than do women. Mechanistic details of this sexual dimorphism in RV remodeling are incompletely understood. We sought to elucidate the cardiac pathophysiology underlying the sex-specific RV remodeling phenotypes, RV failure (RVF) versus compensated RVD.MethodsWe subjected male (M-) and female (F-) adult mice to moderate pulmonary artery banding (PAB) for 9wks. Mice underwent serial echocardiography, cardiac MRI, RV pressure-volume loop recordings, histologic and molecular analyses.ResultsM-PAB developed severe RVD with RVF, increased RV collagen deposition and degradation, extracellular matrix (ECM) instability, and activation and recruitment of macrophages. Despite the same severity and chronicity of RV pressure overload, F-PAB had more stable ECM, lacked chronic inflammation, and developed mild RVD without RVF.ConclusionsECM destabilization and chronic activation of recruited macrophages are associated with maladaptive RV remodeling and RVF in male PAB mice. Adaptive RV remodeling of female PAB mice lacked these histopathologic changes. Our findings suggest that these two pathophysiologic processes likely contribute to the sexual dimorphism of RV pressure overload remodeling. Further mechanistic studies are needed to assess their pathogenic roles and potential as targets for RVD therapy and RVF prevention.CLINICAL PERSPECTIVEWhat is new?In a mouse model of pure PH, males but not females showed an association between ECM instability, chronic inflammation with activation of recruited macrophages, and severe RV dysfunction and failure.What are the clinical implications?In male HF and PH patients, enhancing ECM stability and countering the recruitment and activation of macrophages may help preserve RV function such that RVF can be prevented or delayed. Further preclinical mechanistic studies are needed to assess the therapeutic potential of such approaches.RESEARCH PERSPECTIVEWhat new question does this study raise? What question should be addressed next?What mechanisms regulate RV ECM stability and macrophage recruitment and activation in response to chronic RV pressure overload? Are these regulatory mechanisms dependent upon or independent of sex hormone signaling?
Opposites attract: Multiple evidence of sexual antagonistic coevolution driving extreme male-biased sexual size dimorphism inPanopeus meridionalis
Authors: Farias N.E. , Ribeiro P. , Lancia J.P. , Luppi T. 
Published: April 2024

ABSTRACTExplanations for the evolution of male-biased size dimorphism (MBSSD) traditionally focus on male competition and female choice, overlooking the alternative that larger males may be better at coercing females into mating. While displaying considerable diversity, ‘true crabs’ (Eubrachyura) share common traits that theoretically should promote the evolution of coercive mating strategies. Despite this, there is a conspicuous lack of studies investigating this aspect. We investigated several reproductive and life history traits ofPanopeus meridionalis(a mud crab that exhibits extreme MBSSD) to assess whether the specific set of characters is consistent with the hypothesis of sexual antagonistic coevolution at place. We found that the high MBSSD is likely driven by sexual conflict, where males use their size to coerce females into mating. Experimental matings involved male aggression towards females. Females first resist male attempts, but are ultimately subdued. Mating is relatively brief and there is no evident pre or post copulatory guarding. The female reproductive tract lacks complex structures for long-term sperm storage or manipulation, and given the small size of seminal receptacles related to male sperm load capacity, it is unlikely for females to store sperm from multiple partners. All considered, the evidence suggests that females have limited control over paternity and support the existence of an intrinsically coercive mating system inP. meridionalis. We propose this species as an interesting model for studying the resolution of sexual conflict through antagonistic coevolution and selection in the highly diverse group of true crabs.
Intensive Versus Conservative Blood Pressure Lowering after Endovascular Therapy in Stroke: a meta-analysis of randomized controlled trials
Authors: Mansoor Ahmed Naji , Choudhary Vatsalya , Nasser Zain Mohammad , Jain Muskan , Sharma Dhruvikumari Dayanand , Villegas Mateo Jaramillo , Janarthanam Sujaritha , Ayyan Muhammad , Nimal Simran Ravindra , Cheema Huzaifa Ahmad , Ehsan Muhammad , Rehman Muhammad Aemaz Ur , Dani Sourbha S. 
Published: April 2024

AbstractBackgroundThe optimum systolic blood pressure after endovascular thrombectomy for acute ischemic stroke is uncertain. We aimed to perform an updated meta-analysis of randomized controlled trials to evaluate the safety and efficacy of more intensive blood pressure management as compared to less intensive blood pressure management.MethodsWe searched various electronic databases including Embase, MEDLINE (via PubMed), and CENTRAL to retrieve relevant randomized controlled trials (RCTs) on the clinical effects of more intensive blood pressure management after endovascular thrombectomy as compared to the less intensive management. We assessed the risk of bias using the revised Cochrane “Risk of bias” tool for randomized trials (RoB 2.0), calculated risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) with 95% CI for continuous outcomes.ResultsOur meta-analysis included 4 RCTs with a total of 1560 patients. According to our analysis, more intensive blood pressure management was associated with a statistically significant decrease in the number of patients showing functional independence (modified Rankin scale mRS score=0-2) at 90 days (RR 0.81; CI = 0.72-0.91; I2= 12%). Regarding 90-day mortality, our pooled results from three RCTs showed no statistically significant difference between the more intensive blood pressure management group and the less intensive blood pressure management group (RR 1.17; CI = 0.90-1.52; I2= 0%). There was no statistically significant difference between the two groups regarding the incidence of intracerebral hemorrhage (ICH) (RR 1.05; CI = 0.90-1.23; I2= 0%) and the incidence of symptomatic intracerebral hemorrhage (sICH) (RR 1.10; CI = 0.76-1.60; I2= 0%).ConclusionAccording to our meta-analysis, no benefit of intensive lowering of blood pressure was observed in terms of functional independence at 90 days, mortality rates, and incidence of intracerebral hemorrhage. Future large-scale trials should focus on other interventions to improve prognosis in these patients.
Can self-testing be enhanced to hasten safe return of healthcare workers in pandemics? Random order, open label trial using two manufacturers’ SARS-CoV-2 lateral flow devices concurrently
Authors: Zhang Xingna , Cheyne Christopher P , Jones Christopher , Humann Michael , Leeming Gary , Smith Claire , Hughes David M , Burnside Girvan , Dodd Susanna , Penrice-Randal Rebekah , Dong Xiaofeng , Semple Malcolm G , Neal Tim , Tunkel Sarah , Fowler Tom , Turtle Lance , Garcia-Finana Marta , Buchan Iain E 
Published: April 2024

AbstractBackgroundCovid-19 healthcare worker testing, isolation and quarantine policies had to balance risks to patients from the virus and from staff absence. The emergence of the Omicron variant led to dangerous levels of key-worker absence globally.We evaluated whether using two manufacturers’ lateral flow tests (LFTs) concurrently improved SARS-CoV-2 Omicron detection and was acceptable to hospital staff. In a nested study, to understand risks of return to work after a 5-day isolation/quarantine period, we examined virus culture 5-7 days after positive test or significant exposure.MethodsFully-vaccinated Liverpool (UK) University Hospitals staff participated (February-May 2022) in a random-order, open-label trial testing whether dual LFTs improved SARS-CoV2 detection, and whether dual swabbing was acceptable to users. Participants used nose-throat swab Innova and nose-only swab Orient Gene LFTs in daily randomised order for 10 days. A user-experience questionnaire was administered on exit. Selected participants gave swabs for viral culture on Days 5-7. Cultures were considered positive if cytopathic effect was apparent or SARs-COV2 N gene sub-genomic RNA was detected.Results226 individuals reported 1466 pairs of LFT results. Tests disagreed in 127 cases (8.7%). Orient Gene was more likely (78 cf. 49, P=0.03) to be positive. Orient Gene positive Innova negative result-pairs became more frequent over time (P<0.001). If Innova was swabbed second, it was less likely to agree with a positive Orient Gene result (P=0.005); swabbing first with Innova made no significant difference (P=0.85).Of 311 individuals completing the exit questionnaire, 90.7% reported dual swabbing was easy, 57.1% said it was no barrier to their daily routine and 65.6% preferred dual testing. Respondents had more confidence in dual c.f. single test results (P<0.001).Viral cultures from Days 5-7 were positive for 6/31 (19.4%, 7.5%-37.5%) and indeterminate for 11/31 (35.5%, 19.2%-54.6%) LFT-positive participants, indicating they were likely still infectious.ConclusionsDual brand testing increased LFT detection of SARS-CoV-2 antigen by a small but meaningful margin and was acceptable to hospital workers. Viral cultures demonstrated that policies recommending safe return to work ∼5 days after Omicron infection/exposure were flawed. Key-workers should be prepared for dynamic self-testing protocols in future pandemics.Trial registrationhttps://www.isrctn.com/ISRCTN47058442(IRAS:311842)
When should lockdown be implemented? Devising cost-effective strategies for managing epidemics amid vaccine uncertainty
Authors: Doyle Nathan J. , Cumming Fergus , Thompson Robin N. , Tildesley Michael J. 
Published: April 2024

AbstractDuring an infectious disease outbreak, public health policy makers are tasked with strategically implementing control interventions whilst balancing competing objectives. To provide a quantitative framework that can be used to guide these decisions, it is helpful to devise a clear and specific objective function that can be evaluated to determine the optimal outbreak response. In this study, we have developed a mathematical modelling framework representing outbreaks of a novel emerging pathogen for which non-pharmaceutical interventions (NPIs) are imposed or removed based on thresholds for hospital occupancy. These thresholds are set at different levels to define four unique control strategies. We illustrate that the optimal intervention strategy is contingent on the choice of objective function. Specifically, the optimal strategy depends on the extent to which policy makers prioritise reducing health costs due to infection over the costs associated with control interventions. Motivated by the scenario early in the COVID-19 pandemic, we incorporate the development of a vaccine into our modelling framework and demonstrate that a policy maker's belief about when a vaccine will become available in future, and its eventual coverage (and/or effectiveness), affects the optimal control strategy to adopt early in the outbreak. Furthermore, we show how uncertainty in these quantities can be accounted for when deciding which interventions to introduce. This research highlights the benefits of policy makers being explicit about the precise objectives of introducing interventions.
Measurement of changes to the menstrual cycle: A transdisciplinary systematic review evaluating measure quality and utility for clinical trials
Authors: Mackenzie Amelia C.L. , Chung Stephanie , Hoppes Emily , Mickler Alexandria K. , Cartwright Alice F. 
Published: April 2024

ABSTRACTDespite the importance of menstruation and the menstrual cycle to health, human rights, and sociocultural and economic wellbeing, the study of menstrual health suffers from a lack of funding, and research remains fractured across many disciplines. We sought to systematically review validated approaches to measure four aspects of changes to the menstrual cycle—bleeding, blood, pain, and perceptions—caus ed by any source and used within any field. We then evaluated the measure quality and utility for clinical trials of the identified instruments. We searched MEDLINE, Embase, and four instrument databases and included peer-reviewed articles published between 2006 and 2023 that reported on the development or validation of instruments assessing menstrual changes using quantitative or mixed-methods methodology. From a total of 8,490 articles, 8,316 were excluded, yielding 174 articles reporting on 94 instruments. Almost half of articles were from the United States or United Kingdom and over half of instruments were only in English, Spanish, French, or Portuguese. Most instruments measured bleeding parameters, uterine pain, or perceptions, but few assessed characteristics of blood. Nearly 60% of instruments were developed for populations with menstrual or gynecologic disorders or symptoms. Most instruments had fair or good measure quality or clinical trial utility; however, most instruments lacked evidence on responsiveness, question sensitivity and/or transferability, and only three instruments had good scores of both quality and utility. Although we took a novel, transdisciplinary approach, our systematic review found important gaps in the literature and instrument landscape, pointing towards a need to examine the menstrual cycle in a more comprehensive, inclusive, and standardized way. Our findings can inform the development of new or modified instruments, which—if used across the many fields that study menstrual health and within clinical trials—can contribute to a more systemic and holistic understanding of menstruation and the menstrual cycle.
Consensus recommendations for measuring the impact of contraception on the menstrual cycle in contraceptive clinical trials
Authors: Mackenzie Amelia C. L. , Chung Stephanie , Hoppes Emily , Miller Nora , Burke Anne E. , Achilles Sharon L. , Allen C. Leigh , Bahamondes Luis , Blithe Diana L. , Brache Vivian , Callahan Rebecca L. , Cartwright Alice F. , Clancy Kathryn B. H. , Colli Enrico , Cordova-Gomez Amanda , Costenbader Elizabeth E. , Creinin Mitchell D. , Critchley Hilary O. D. , Doncel Gustavo F. , Dorflinger Laneta J. , Edelman Alison , Faustmann Thomas , Gerlinger Christoph , Haddad Lisa B. , Hennegan Julie , Juliato Cássia Raquel Teatin , Kibira Simon P. S. , Mansour Diana , Martinez Andres , Matteson Kristen A. , Maybin Jacqueline A. , Mickler Alexandria K. , Nanda Kavita , Nwachukwu Chukwuemeka E. , OlaOlorun Funmilola M. , Peine Kevin J. , Polis Chelsea B. , Vieira Carolina Sales , Sitruk-Ware Regine , Smit Jennifer A. , Solomon Marsden , Soule Lisa M. , Taylor Douglas , Tolley Elizabeth E. , Vandeputte Olivia 
Published: April 2024

AbstractObjectiveWe sought to develop consensus recommendations for improved measurement of contraceptive-induced menstrual changes (CIMCs) in contraceptive clinical trials to build upon previous standardization efforts.Study DesignWe undertook a virtual consensus-building process using a modified Delphi approach, incorporating aspects of Nominal Group Technique and the Jandhyala method. The process consisted of four half-day meetings, developing recommendations within five topical working groups, a series of consensus questionnaires to assess recommendation agreement on a 4-point Likert-like scale, and opportunities for input and feedback throughout the process. Recommendations required at least 75% consensus to be included.ResultsOur interdisciplinary group—from 26 organizations and 13 countries in five global regions across academia, nonprofit research organizations, the pharmaceutical industry, and funding agencies— developed 44 consensus recommendations. These included recommendations on standardization, patient-reported outcome measure development aligned with current regulatory guidance, trial design, protocol development, participant recruitment, data collection, data analysis, and areas for exploratory research. Seven recommendations were deemed a priority by over 85% of our group.ConclusionUsing a formal consensus-building process, we reached high levels of agreement around recommendations for more standardized and patient-centered measurement of CIMCs in contraceptive clinical trials, now and in the future.Implications statementConsensus recommendations on measuring bleeding changes and related outcomes in contraceptive clinical trials can improve reporting of standardized, patient-centered outcomes in future product labeling. These improvements can enable providers to offer more relevant counseling on contraceptives and permit greater comparability and data synthesis across trials to inform clinical guidance.
Integrity of dopaminergic terminals in the caudate nucleus is relevant for rest tremor in Parkinson’s disease
Authors: Mendonça Marcelo D. , Ferreira Pedro , Oliveira Francisco , Barbosa Raquel , Meira Bruna , Costa Durval , Oliveira-Maia Albino , Alves da Silva Joaquim 
Published: April 2024

AbstractResting tremor (RT) is a Parkinson’s disease (PD) symptom whose relationship with the dopaminergic system remains puzzling. To clarify this relation, we analysed data from 432 subjects from the PPMI (Parkinson’s Progression Markers Initiative) database, a second cohort of 57 PD patients and controls and a third cohort of 86 subjects referred for dopamine transporter single-photon emission computed tomography (DaT-SPECT). Caudate, but not putamen binding potential (CBP, PBP) was higher in patients with RT. The presence of a higher CBP at the baseline and a relative sparing of CBP were related to the development of RT in the 2ndyear. In the smaller cohorts, a 4-6 Hz oscillation-based metric extracted from inertial sensors correlated with RT amplitude and distinguished groups with DA denervation from controls. The same metric was correlated with CBP, but not PBP in subjects with a denervated DaT-SPECT.In silicomodelling uncovered that higher CBP in patients with RT was fundamental to explain the associations and correlations between RT and DaT-SPECT described in our and other datasets. These results support that the integrity of caudate dopaminergic terminals could be relevant for RT pathophysiology. Unbiased assessment methods, such as inertial sensors, can be important to understand PD pathophysiology.
Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by modulating the tumor immune microenvironment
Authors: Li Jin , Dhilipkannah Pushpa , Holden Van K , Sachdeva Ashutosh , Todd Nevins W , Jiang Feng 
Published: April 2024

ABSTRACTAfrican American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidate the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets.
TCR clustering by contrastive learning on antigen specificity
Authors: Pertseva Margarita , Follonier Oceane , Scarcella Daniele , Reddy Sai T. 
Published: April 2024

AbstractEffective clustering of T-cell receptor (TCR) sequences could be used to predict their antigen-specificities. TCRs with highly dissimilar sequences can bind to the same antigen, thus making their clustering into a common antigen group a central challenge. Here, we develop TouCAN, a method that relies on contrastive learning and pre-trained protein language models to perform TCR sequence clustering and antigen-specificity predictions. Following training, TouCAN demonstrates the ability to cluster highly dissimilar TCRs into common antigen groups. Additionally, TouCAN demonstrates TCR clustering performance and antigen-specificity predictions comparable to other leading methods in the field.
Flow zoometry ofDrosophila
Authors: Peterson Walker , Arenson Joshua , Hata Soichiro , Kacenauskaite Laura , Kobayashi Tsubasa , Otsuka Takuya , Wang Hanqing , Wada Yayoi , Hiramatsu Kotaro , He Zhikai , Clement Jean-Emmanuel , Zhang Chenqi , Hu Chenglang , McCann Phillip , Kanazawa Hayato , Nagasaka Yuzuki , Uechi Hiroyuki , Watanabe Yuh , Yamamura Ryodai , Hayashi Mika , Nakagawa Yuta , Huang Kangrui , Kanno Hiroshi , Zhou Yuqi , Ding Tianben , Herbig Maik , Makino Shimpei , Nonaga Shunta , Takami Ryosuke , Kanca Oguz , Tabata Koji , Amaya Satoshi , Furusawa Kotaro , Ishii Kenichi , Emoto Kazuo , Arai Fumihito , Cagan Ross , Di Carlo Dino , Igaki Tatsushi , Kuranaga Erina , Yamamoto Shinya , Bellen Hugo J , Komatsuzaki Tamiki , Sonoshita Masahiro , Goda Keisuke 
Published: April 2024

ABSTRACTDrosophilaserves as a highly valuable model organism across numerous fields including genetics, immunology, neuroscience, cancer biology, and developmental biology. Central toDrosophila-based biological research is the ability to perform comprehensive genetic or chemical screens. However, this research is often limited by its dependence on laborious manual handling and analysis, making it prone to human error and difficult to discern statistically significant or rare events amid the noise of individual variations resulting from genetic and environmental factors. In this article we present flow zoometry, a whole-animal equivalent of flow cytometry for large-scale, individual-level, high-content screening ofDrosophila. Our flow zoometer automatically clears the tissues ofDrosophila melanogaster, captures three-dimensional (3D) multi-color fluorescence tomograms of single flies with single-cell volumetric resolution at an unprecedented throughput of over 1,000 animals within 48 hours (24 hr for clearing; 24 hr for imaging), and performs AI-enhanced data-driven analysis – a task that would traditionally take months or years with manual techniques. To demonstrate its broad applications, we employed the flow zoometer in various laborious screening assays, including those in toxicology, genotyping, and tumor screening. Flow zoometry represents a pivotal evolution in high-throughput screening technology: previously from molecules to cells, now from cells to whole animals. This advancement serves as a foundational platform for “statistical spatial biology”, to improve empirical precision and enable serendipitous discoveries across various fields of biology.