bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating CD4+ T cells in people with HIV and history of pulmonary tuberculosis have more intact HIV DNA
Authors: Juste Marc Antoine Jean , Joseph Yvetot , Lespinasse Dominique , Apollon Alexandra , Jamshidi Parmida , Lee Myung Hee , Ward Maureen , Brill Esther , Duffus Yanique , Chukwukere Uche , Danesh Ali , Alberto Winiffer Conce , Fitzgerald Daniel W. , Pape Jean W. , Jones R. Brad , Dupnik Kathryn 
Published: March 2024

ABSTRACTBackgroundThe primary barrier to curing HIV infection is the pool of intact HIV proviruses integrated into host cell DNA throughout the bodies of people living with HIV (PLHIV), called the HIV reservoir. Reservoir size is impacted by the duration of HIV infection, delay in starting antiretroviral therapy (ART), and breakthrough viremia during ART. The leading infectious cause of death worldwide for PLHIV is TB, but we don’t know how TB impacts the HIV reservoir.MethodsWe designed a case-control study to compare HIV provirus-containing CD4 in PLHIV with vs. without a history of active TB disease. Study participants in the pilot and confirmatory cohort were enrolled at GHESKIO Centers in Port au Prince, Haiti. Intact and non-intact proviral DNA were quantified using droplet digital PCR of PBMC-derived CD4 cells. For a subset, Th1 and Th2 cytokines were assayed in plasma. Kruskal-Wallis tests were used to compare medians with tobit regression for censoring.ResultsIn the pilot cohort, we found that PLHIV with history of active pulmonary TB (n=20) had higher intact provirus than PLHIV without history of active TB (n=47) (794 vs 117 copies per million CD4, respectively; p<0.0001). In the confirmatory cohort, the quantity of intact provirus was higher in the TB group (n=13) compared with the non-TB group (n=18) (median 102 vs. 0 intact provirus per million CD4, respectively p=0.03). Additionally, we found that the frequencies of CD4+ T cells with any detectable proviral fragment was directly proportional to the levels of IL1B (p= 0.0025) and IL2 (p=0.0002).ConclusionsThis is the first assessment of HIV provirus using IPDA in a clinical cohort from a resource limited setting, and the finding of larger reservoir in PLHIV with history of TB has significant implications for our understanding of TB-HIV coinfection and HIV cure efforts in TB-endemic settings.
A meta-analysis approach to gene regulatory network inference identifies key regulators of cardiovascular diseases
Authors: Pepe G. , Appierdo R. , Ausiello G. , Helmer-Citterich M. , Gherardini PF. 
Published: March 2024

AbstractCardiovascular diseases (CVDs) represent a major concern for global health whose mechanistic understanding is complicated by a complex interplay between genetic predisposition and environmental factors.Specifically, heart failure (HF), encompassing dilated cardiomyopathy (DC), ischemic cardiomyopathy (ICM), and hypertrophic cardiomyopathy (HCM), is a topic of substantial interest in basic and clinical research. Here we used a Partial Correlation Coefficient-based algorithm (PCC) within the context of a meta-analysis framework, to construct a Gene Regulatory Network (GRN) that identifies key regulators whose activity is perturbed in Heart Failure. By integrating data from multiple independent studies, our approach unveiled crucial regulatory associations between transcription factors (TFs) and structural genes, emphasizing their pivotal roles in regulating metabolic pathways, such as fatty acid metabolism, oxidative stress response, epithelial-to-mesenchymal transition, and coagulation. In addition to known associations, our analysis also identified novel regulators, including the identification of TFs FPM315 and MOVO-B, which are implicated in dilated cardiomyopathies, and TEAD1 and TEAD2 in both dilated and ischemic cardiomyopathies. Moreover, we uncovered alterations in adipogenesis and oxidative phosphorylation pathways in hypertrophic cardiomyopathy, and discovered a role for IL2 STAT5 signaling in heart failure.Our findings underscore the importance of TFs activity in the initiation and progression of cardiac disease, highlighting their potential as pharmacological targets.
Mitochondrial dynamics regulate cell size in the developing cochlea
Authors: O’Sullivan James D. B. , Terry Stephen , Scott Claire A. , Bullen Anwen , Jagger Daniel J. , Mann Zoë F. 
Published: March 2024

AbstractIn multicellular tissues, cell size and shape are intricately linked with physiological function. In the vertebrate auditory organ, the neurosensory epithelium develops as a mosaic of sensory hair cells (HCs), and their glial-like supporting cells (SCs), which have distinct morphologies at different frequency positions along its tonotopic long axis. In the chick cochlea, the basilar papilla (BP), proximal (high-frequency) HCs are larger than their distal (low-frequency) counterparts, a morphological feature essential for frequency tuning. Mitochondrial dynamics, which constitute the equilibrium between fusion and fission, regulate differentiation and functional refinement across a variety of cell types. We investigate this a potential mechanism for cell size regulation in developing HCs. Using live imaging in intact BP explants, we identify distinct remodelling of mitochondrial networks in proximal compared to distal HCs. Manipulating mitochondrial dynamics in developing HCs alters their normal morphology along the proximal-distal (tonotopic) axis. Inhibition of the mitochondrial fusion machinery decreased proximal HC size, whilst promotion of fusion increased the distal HC size. We identify mitochondrial dynamics as a key regulator of HC size and morphology in developing inner ear epithelia.Summary StatementMitochondrial remodelling drives developmental changes in cell size in the auditory sensory epithelium. Our data reveal a fundamental mechanism regulating cell size and frequency-place coding in the developing cochlea.
Astrocytes in the mouse suprachiasmatic nuclei respond directly to glucocorticoids feedback
Authors: Händler Kristian , Sreenivasan Varun K.A. , Pilorz Violetta , Bringas Jon Olano , Castañondo Laura Escobar , Bengoa-Vergniory Nora , Oster Henrik , Spielmann Malte , Astiz Mariana 
Published: March 2024

AbstractThe circadian timing system anticipates daily recurring changes in the environment to synchronize physiology. In mammals, the master pacemaker is the hypothalamic suprachiasmatic nuclei (SCN), which synchronizes “wake” functions by inducing the circadian release of Glucocorticoids (GCs) from the adrenal gland. GCs peak right before the active phase and set the time of peripheral clocks, however, it is still unclear whether the SCN respond to GCs feedback. While GCs influence directly the SCN during the perinatal period, the adult circuit is considered to be resistant to them, suggesting a reduction of GCs-sensitivity along development. To understand this mechanism, we followed the expression of GC receptor (GR) along mouse SCN development with single-cell resolution and show that GR is up-regulated in astrocytes as the circuit matures. We providein vivoandin vitroevidence that the adult SCN stays responsive to circulating GCs through the activation of GR in astrocytes. Astrocytes’ communication is necessary to induce the GC-dependent shift on the SCN clock. Our data provides insight into the development of the SCN and highlight a new role of astrocytes as time-keepers in the adult. This finding might shed light on how the circadian system adapts to jetlag or shift work.
Human Pluripotent Stem Cell Derived Organoids Reveal a Role for WNT Signaling in Dorsal-Ventral Patterning of the Hindgut
Authors: Qu Na , Daoud Abdelkader , Kechele Daniel O. , Múnera Jorge O. 
Published: March 2024

SummaryThe cloaca is a transient structure that forms in the terminal hindgut giving rise to the rectum dorsally and the urogenital sinus ventrally. Similarly, human hindgut cultures derived from human pluripotent stem cells generate human colonic organoids (HCOs) which also contain co-developing urothelial tissue. In this study, our goal was to identify pathways involved in cloacal patterning and apply this to human hindgut cultures. RNA-seq data comparing dorsal versus ventral cloaca in e10.5 mice revealed that WNT signaling was elevated in the ventral versus dorsal cloaca. Inhibition of WNT signaling in hindgut cultures biased their differentiation towards a colorectal fate. WNT activation biased differentiation towards a urothelial fate, giving rise to human urothelial organoids (HUOs). HUOs contained cell types present in human urothelial tissue. Based on our results, we propose a mechanism whereby WNT signaling patterns the ventral cloaca, prior to cloacal septation, to give rise to the urogenital sinus.
Targeting G9a translational mechanism of SARS-CoV-2 pathogenesis for multifaceted therapeutics of COVID-19 and its sequalae
Authors: Muneer Adil , Xie Ling , Xie Xuping , Zhang Feng , Wrobel John A. , Xiong Yan , Yu Xufen , Wang Charles , Gheorghe Ciprian , Wu Ping , Song Juan , Ming Guo-Li , Jin Jian , Song Hongjun , Shi Pei-Yong , Chen Xian 
Published: March 2024

ABSTRACTBy largely unknown mechanism(s), SARS-CoV-2 hijacks the host translation apparatus to promote COVID-19 pathogenesis. We report that the histone methyltransferase G9a noncanonically regulates viral hijacking of the translation machinery to bring about COVID-19 symptoms of hyperinflammation, lymphopenia, and blood coagulation. Chemoproteomic analysis of COVID-19 patient peripheral mononuclear blood cells (PBMC) identified enhanced interactions between SARS-CoV-2-upregulated G9a and distinct translation regulators, particularly the N6-methyladenosine (m6A) RNA methylase METTL3. These interactions with translation regulators implicated G9a in translational regulation of COVID-19. Inhibition of G9a activity suppressed SARS-CoV-2 replication in human alveolar epithelial cells. Accordingly, multi-omics analysis of the same alveolar cells identified SARS-CoV-2-induced changes at the transcriptional, m6A-epitranscriptional, translational, and post-translational (phosphorylation or secretion) levels that were reversed by inhibitor treatment. As suggested by the aforesaid chemoproteomic analysis, these multi-omics-correlated changes revealed a G9a-regulated translational mechanism of COVID-19 pathogenesis in which G9a directs translation of viral and host proteins associated with SARS-CoV-2 replication and with dysregulation of host response. Comparison of proteomic analyses of G9a inhibitor-treated, SARS-CoV-2 infected cells, orex vivoculture of patient PBMCs, with COVID-19 patient data revealed that G9a inhibition reversed the patient proteomic landscape that correlated with COVID-19 pathology/symptoms. These data also indicated that the G9a-regulated, inhibitor-reversed, translational mechanism outperformed G9a-transcriptional suppression to ultimately determine COVID-19 pathogenesis and to define the inhibitor action, from which biomarkers of serve symptom vulnerability were mechanistically derived. This cell line-to-patient conservation of G9a-translated, COVID-19 proteome suggests that G9a inhibitors can be used to treat patients with COVID-19, particularly patients with long-lasting COVID-19 sequelae.
EVALUATION OF THE RELATIONSHIP BETWEEN ADVANCED MATERNAL AGE AND PREGNANCY OUTCOME: A SCOPING REVIEW
Authors: Eze Innocent Okafor , Ezechi Oliver Chukwujiekwu , Mohammed Ahmadu Shehu , Nwagha Uchenna Ifeanyi 
Published: March 2024

AbstractBackgroundChildbirth at advanced maternal age (AMA) is increasing among women, and some studies have shown adverse outcomes. There is a need to map evidence on the subject to harness findings and identify research gaps for further studies. This scoping review aims to examine pertinent studies on AMA and its impact on pregnancy outcomes.MethodsThe Preferred Reporting Item for Systematic Review and Meta-Analysis (PRISMA) chart is employed for systematic data extraction. This review draws from Google Scholar, the Cochrane Library, Medline (via PubMed), and Embase (via OVID). For inclusion in this scoping review, articles must thoroughly examine and elucidate the effects, impacts, and relationships between advanced maternal age and pregnancy outcomes. A crucial prerequisite is that the articles undergo a peer-review process to ensure the reliability and credibility of the presented information. For this review, advanced maternal age is defined explicitly as women aged ≥35. However, studies focusing on women aged ≥40 are also considered, mainly if they are high quality. In terms of research methodology, both primary and secondary research will be eligible, encompassing systematic reviews and meta-analyses. This broad inclusion aims to capture a comprehensive overview of the existing literature on the subject. Furthermore, articles must be presented in the English language to facilitate a standardized and accessible analysis. This criterion ensures that language barriers do not impede the review’s ability to synthesize relevant information effectively.ResultsThere are significant associations between advanced maternal age and poor pregnancy outcomes, even when adjusted for confounders.ConclusionsThe adverse pregnancy outcome due to maternal age alone may be due to placental dysfunction resulting from a relative deficiency in maternal cardiovascular adaptations to pregnancy, and this provides a window for further studies.
Uncovering clinical rehabilitation technology trends: field observations, mixed methods analysis, and data visualization
Authors: Celian Courtney , Redd Hannah , Smaller Kevin , Ryali Partha , Patton James L. , Reinkensmeyer David J. , Rafferty Miriam R. 
Published: March 2024

ABSTRACTObjectiveTo analyze real-world rehabilitation technology (RT) use, with a view toward enhancing RT development and adoption.DesignA convergent, mixed-methods study using direct field observations, semi-structured templates, and summative content analysis.SettingTen neurorehabilitation units in a single health system.Participants3 research clinicians (1OT, 2PTs) observed ∼60 OTs and 70 PTs in inpatient; ∼18 OTs and 30 PTs in outpatient.InterventionsNot applicableMain Outcome MeasuresCharacteristics of RT, time spent setting up and using RT, and clinician behaviors.Results90 distinct devices across 15 different focus areas were inventoried. 329 RT-uses were documented over 44 hours with 42% of inventoried devices used. RT was used more during interventions (72%) than measurement (28%). Intervention devices used frequently were balance/gait (39%), strength/endurance (30%), and transfer/mobility training (16%). Measurement devices were frequently used to measure vitals (83%), followed by grip strength (7%), and upper extremity function (5%). Device characteristics were predominately AC-powered (56%), actuated (57%), monitor-less (53%), multi-use (68%), and required little familiarization (57%). Set-up times were brief (mean ± SD = 3.8±4.21 and 0.8±1.3 for intervention and measurement, respectively); more time was spent with intervention RT (25.6±15) than measurement RT (7.3±11.2). RT nearly always involved verbal instructions (72%) with clinicians providing more feedback on performance (59.7%) than on results (30%). Therapists’ attention was split evenly between direct attention towards the patient during clinician treatment (49.7%) and completing other tasks such as documentation (50%).ConclusionsEven in a tech-friendly hospital, majority of available RT were observed un-used, but identifying these usage patterns is crucial to predict eventual adoption of new designs from earlier stages of RT development. An interactive data visualization page supplement is provided to facilitate this study.
Fit for growing old? Financial protection before and after Indonesia’s national health insurance scheme – a repeated cross-section study
Authors: Tampubolon Gindo 
Published: March 2024

AbstractThe world is ageing with unprecedented momentum, and large global south nations are ageing at higher speed than their northern peers. They have grown old while they have not grown rich, straining their health systems’ ability to deliver financial protection. This work aimed to assess whether Indonesia’s health insurance scheme, seven years on, has delivered equal protection for families with older members (over 60 years) as for other families.MethodsBefore-and-after observation study is designed to estimate how much difference the Scheme made to probabilities of catastrophic payment and financial impoverishment for the two family types. As in recent assessments, two national socioeconomic surveys were used (2013, 2021). Two level observations came from 622,125 families residing in 514 districts across the archipelago. Financial protection indicators against catastrophic payment and impoverishment were constructed following recent works. I estimated two level probit models, then plotted marginal probabilities of financial protection. A sensitivity analysis was conducted with the standard financial protection indicator.FindingAfter the Scheme, financial hardship for all family types has reduced by 19%. But families with older members (compared to other families) have an additional 0.7% risk of incurring catastrophic payment or financial impoverishment. And social and spatial inequalities in health persist.DiscussionWhile the Scheme has markedly improved financial protection for all, families with older members remain at higher risk of being unprotected. The global south can prepare for an ageing world by monitoring financial protection and its social determinants and systematically distinguishing families with older members.
Uterine Fibroids and Hypertensive Disorders in Pregnancy: A Systematic Review and Meta-Analysis
Authors: Nasab Susan , Gough Ethan K , Nylander Elisabeth , Borahay Mostafa , Segars James , Baker Valerie , Wang Xiaobin , Cameron Katherine 
Published: March 2024

CapsuleIn this study the presence of uterine fibroids was significantly associated with an increased risk of development of hypertensive disorders of pregnancy even when accounting for age and BMI in meta-regression. This finding has potential implications for risk stratification and monitoring for hypertension during pregnancy in this population.ObjectiveTo examine the association between uterine fibroids and the development of hypertensive disorders in pregnancy.Data sourcesCochrane, Embase, PubMed, MEDLINE, Scopus, and Web of Science databases were searched from inception through April 2023.Study Selection and SynthesisCohort, case-control, or case series studies including uterine fibroid status and hypertensive disorders of pregnancy status were included. The comparison group was pregnant women without uterine fibroids. Inverse-variance weighted random effects models were used to pool RR and OR estimates separately. Age and BMI were explored as potential sources of heterogeneity using inverse-variance weighted meta-regression.Main OutcomesHypertensive disorders of pregnancy (HDP) defined as gestational hypertension, pre-eclampsia, eclampsia, superimposed preeclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome.ResultsA total of 17 studies were included (Total N=1,374,395 participants, N=64,968 with uterine fibroids). Thirteen studies were retrospective cohorts and four were case-control studies. Women with uterine fibroids had a significantly higher risk of hypertensive disorders in pregnancy compared to women without uterine fibroids with RR 1.74 (95% CI 1.33-2.27, p<0.01), and OR 2.87 (95% CI 1.38-5.97, p<0.01), in cohort studies and case-control studies, respectively. In meta-regression analyses, age did not significantly change the positive association between uterine fibroids and hypertensive disorders in pregnancy.ConclusionUterine fibroids were associated with an increased risk of hypertensive disorders of pregnancy when all available literature was synthesized, including when shared risk factors are examined in meta-regression analyses.RelevanceIf confirmed in future studies, investigations into the mechanisms of this association are needed as this finding potentially has implications for risk stratification and monitoring for hypertensive disorders of pregnancy in this population.Trial RegistrationPROSPERO, ID # 331528
Sortase A-based post-translational modifications on encapsulin nanocompartments
Authors: Helalat Seyed Hossein , Sun Yi , Tellez Rodrigo 
Published: March 2024

AbstractProtein-based encapsulin nanocompartments, known for their well-defined structures and versatile functionalities, present promising opportunities in the biotechnology and nanomedicine area. In this investigation, we effectively developed a sortase A-mediated protein ligation system inE. colito site-specifically attach target proteins to encapsulin, both internally and on its surfaces without any furtherin vitrosteps. We explored the potential applications of fusing sortase enzyme and a protease for post-translational ligation of encapsulin to a green fluorescent protein (GFP) and anti-CD3 scFv. Our results demonstrated that this system could attach other proteins to the nanoparticles’ exterior surfaces without adversely affecting their folding and assembly processes. Additionally, this system enabled the attachment of proteins inside encapsulins which varied shapes and sizes of the nanoparticles due to cargo overload. This research opens up avenues for further exploration of the applications and engineering possibilities of encapsulins in the rapidly advancing field of nanotechnology.
Developmental trajectory of cortical somatostatin interneuron function
Authors: Wang Alex , Ferguson Katie A. , Gupta Jyoti , Higley Michael J. , Cardin Jessica A. 
Published: March 2024

SummaryGABAergic inhibition is critical to the proper development of neocortical circuits. However, GABAergic interneurons are highly diverse and the developmental roles of distinct inhibitory subpopulations remain largely unclear. Dendrite-targeting, somatostatin-expressing interneurons (SST-INs) in the mature cortex regulate synaptic integration and plasticity in excitatory pyramidal neurons (PNs) and exhibit unique feature selectivity. Relatively little is known about early postnatal SST-IN activity or impact on surrounding local circuits. We examined juvenile SST-INs and PNs in mouse primary visual cortex. PNs exhibited stable visual responses and feature selectivity from eye opening onwards. In contrast, SST-INs developed visual responses and feature selectivity during the third postnatal week in parallel with a rapid increase in excitatory synaptic innervation. SST-INs largely exerted a multiplicative effect on nearby PN visual responses at all ages, but this impact increased over time. Our results identify a developmental window for the emergence of an inhibitory circuit mechanism for normalization.