bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Learning Estimation of Small Airways Disease from Inspiratory Chest CT is Associated with FEV1Decline in COPD
Authors: Chaudhary Muhammad F. A. , Awan Hira A. , Gerard Sarah E. , Bodduluri Sandeep , Comellas Alejandro P. , Barjaktarevic Igor Z. , Barr R. Graham , Cooper Christopher B. , Galban Craig J. , Han MeiLan K. , Curtis Jeffrey L. , Hansel Nadia N. , Krishnan Jerry A. , Menchaca Martha G. , Martinez Fernando J. , Ohar Jill , Vargas Buonfiglio Luis G. , Paine Robert , Bhatt Surya P. , Hoffman Eric A. , Reinhardt Joseph M. 
Published: September 2024

ABSTRACTRationaleQuantifying functional small airways disease (fSAD) requires additional expiratory computed tomography (CT) scan, limiting clinical applicability. Artificial intelligence (AI) could enable fSAD quantification from chest CT scan at total lung capacity (TLC) alone (fSADTLC).ObjectivesTo evaluate an AI model for estimating fSADTLCand study its clinical associations in chronic obstructive pulmonary disease (COPD).MethodsWe analyzed 2513 participants from the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS). Using a subset (n= 1055), we developed a generative model to produce virtual expiratory CTs for estimating fSADTLCin the remaining 1458 SPIROMICS participants. We compared fSADTLCwith dual volume, parametric response mapping fSADPRM. We investigated univariate and multivariable associations of fSADTLCwith FEV1, FEV1/FVC, six-minute walk distance (6MWD), St. George’s Respiratory Questionnaire (SGRQ), and FEV1decline. The results were validated in a subset (n= 458) from COPDGene study. Multivariable models were adjusted for age, race, sex, BMI, baseline FEV1, smoking pack years, smoking status, and percent emphysema.Measurements and Main ResultsInspiratory fSADTLCwas highly correlated with fSADPRMin SPIROMICS (Pearson’s R = 0.895) and COPDGene (R = 0.897) cohorts. In SPIROMICS, fSADTLCwas associated with FEV1(L) (adj.β = −0.034,P< 0.001), FEV1/FVC (adj.β = −0.008,P< 0.001), SGRQ (adj.β = 0.243,P< 0.001), and FEV1decline (mL / year) (adj.β = −1.156,P< 0.001). fSADTLCwas also associated with FEV1(L) (adj.β = −0.032,P< 0.001), FEV1/FVC (adj.β = −0.007,P< 0.001), SGRQ (adj.β = 0.190,P= 0.02), and FEV1decline (mL / year) (adj.β = - 0.866,P= 0.001) in COPDGene. We found fSADTLCto be more repeatable than fSADPRMwith intraclass correlation of 0.99 (95% CI: 0.98, 0.99) vs. 0.83 (95% CI: 0.76, 0.88).ConclusionsInspiratory fSADTLCcaptures small airways disease as reliably as fSADPRMand is associated with FEV1decline.Funding SourceThis work was supported by NHLBI grants R01 HL142625, U01 HL089897 and U01 HL089856, by NIH contract 75N92023D00011, and by a grant from The Roy J. Carver Charitable Trust (19-5154). The COPDGene study (NCT00608764) has also been supported by the COPD Foundation through contributions made to an Industry Advisory Committee that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion.
Rapid Decline of Mpox Antibody Responses Following MVA-BN Vaccination
Authors: Collier Ai-ris Y. , McMahan Katherine , Jacob-Dolan Catherine , Liu Jinyan , Borducchi Erica N , Moss Bernard , Barouch Dan H. 
Published: September 2024

AbstractThe replication-incompetent modified vaccinia Ankara-Bavarian Nordic vaccine (MVA-BN; Jynneos) was deployed during the 2022 clade IIb mpox outbreak. On August 14, 2024, the World Health Organization declared the mpox clade Ib outbreak in the Democratic Republic of the Congo a public health emergency of international concern, which has raised the question about the durability of vaccine immunity after MVA-BN vaccination. In this study, we show that the MVA-BN vaccine generated mpox serum antibody responses that largely waned after 6-12 months.
The Practice of Gender and Protection Mainstreaming in Health Response in Humanitarian Crisis - A Case Study from the Refugee Camps in Cox’s Bazar, Bangladesh
Authors: Halder Charls Erik 
Published: September 2024

AbstractBackgroundThe health system is required to be safe, equitable, and accessible to all ages, gender, and vulnerable groups, including older persons and persons with disability, and address their specific needs and concerns. However, limited evidence is available on the effectiveness and practicality of gender and protection mainstreaming interventions in health response in humanitarian crises.ObjectiveThe overall objective of the research was to explore practices, gaps, and challenges and generate recommendations regarding gender and protection mainstreaming in health response to the Rohingya refugee crisis in Cox’s Bazar, Bangladesh.MethodologyThe research employed a qualitative case study design to explore the practice of gender and protection mainstreaming in health response in Cox’s Bazar. Data collection methods include an extensive literature review and in-depth interviews with professionals.ResultThe study found a range of good practices on gender and protection mainstreaming in health response, e.g. placement of a gender action plan, monitoring system for gender and disability inclusion, emergency preparedness and response system, availability of sex-segregated toilets and waiting spaces, availability of gender-based violence service and engagement of female community health workers. The study also revealed some best practices which have the potential to scale up, e,g. psycho-social spaces at health facilities for children, palliative care for terminally ill patients, integrated medical and protection services, and facilitation of community health facility support groups. Critical gaps were found in the areas of women’s leadership, coordination, capacity building, targeted interventions for vulnerable groups, infrastructural adaptation and consultation with the community on their concerns.ConclusionWe urge policymakers, sector coordinators, health program management, healthcare workers, and global stakeholders to address the gaps and challenges, learn and scale up the best practices, and take action to implement the study’s recommendations to maximise gender and protection mainstreaming in health response.
Eye Movements in Silent Visual Speech track Unheard Acoustic Signals and Relate to Hearing Experience
Authors: Benz Kaja Rosa , Hauswald Anne , Suess Nina , Gehmacher Quirin , Demarchi Gianpaolo , Schmidt Fabian , Herzog Gudrun , Rösch Sebastian , Weisz Nathan 
Published: September 2024

AbstractBehavioral and neuroscientific studies have shown that watching a speaker’s lip movements aids speech comprehension. Intriguingly, even when videos of speakers are presented silently, various cortical regions track auditory features, such as the envelope. Recently, we demonstrated that eye movements track low-level acoustic information when attentively listening to speech. In this study we investigated whether ocular speech tracking occurs during visual speech and how it influences cortical silent speech tracking. Furthermore, we compared the data of hearing individuals with congenitally deaf individuals, and those with acquired deafness or hearing loss (DHH; Deaf or hard of hearing) to assess how auditory deprivation (early vs. late onset) affects neural and ocular speech tracking during silent lip-reading. Using magnetoencephalography (MEG), we examined ocular and neural speech tracking of 75 participants observing silent videos of a speaker played forward and backward. Our main finding is a clear ocular unheard speech tracking effect with a dominance <1 Hz, which was not present for the lip movements. Similarly, we observed a <=1.3 Hz effect of neural unheard speech tracking in temporal regions for hearing participants. Importantly, neural tracking was not directly linked to ocular tracking in this study. Strikingly, across different listening groups, deaf participants with auditory listening experience showed higher ocular speech tracking than hearing participants, while no ocular speech tracking effect was revealed for congenitally deaf participants in a very small sample. This study extends our previous work by demonstrating the involvement of eye movements in speech processing, even in the absence of acoustic input.
Smooth muscle Cxcl12 activation is associated with vascular remodeling in flow-induced pulmonary hypertension
Authors: Klouda Timothy , Tsikis Savas T. , Hirsch Thomas I. , Kim Yunhye , Liu Tiffany , Friehs Ingeborg , Shyy John Y.-J. , Visner Gary , Raby Benjamin A , Puder Mark , Yuan Ke 
Published: September 2024

AbstractPatients with congenital heart disease (CHD) resulting in significant left-to-right shunting of blood are at risk for the development of pulmonary arterial hypertension (PAH). The underlying mechanism by which pulmonary overcirculation and shear stress lead to vascular remodeling remains unclear. Our study established a new “two-hit” murine model of severe pulmonary hypertension (PH) by combining left pneumonectomy and exposure to hypoxia (LP/Hx). Utilizing transgenic reporter lines, immunofluorescence staining, and advanced microscopy, we conducted cell-lineage tracing experiments for endothelial cells (ECs), smooth muscle cells (SMCs), and pericytes. We identified that SMCs is a primary contributor to distal arteriolar remodeling after LP/Hx. Subsequent qPCR analysis on isolated cells demonstrated thatCxcl12was upregulated in both ECs and SMCs from LP/Hx animals. Likewise, CXCL12 was overexpressed in the SMC layer of arterioles in patients with acyanotic PAH-CHD. These findings provide novel insights into the contribution of SMCs and Cxcl12 to pulmonary flow-induced vascular remodeling. This newly established murine model of PH will serve as a new tool for research and targeted therapeutics for patients with PAH.
Cancer-immune coevolution dictated by antigenic mutation accumulation
Authors: Wang Long , Morison Christo , Huang Weini 
Published: September 2024

AbstractThe immune system is one of the first lines of defence against the emergence of cancer. When effector cells attempt to suppress the tumour, the cancer cells can respond in kind by evolving methods of escape or inhibition. Knowledge of this coevolutionary system and the selection taking place within it can help us understand tumour-immune dynamics both during tumorigenesis but also when treatments such as immunotherapies are applied. Here, we present an individual-based branching process model of mutation accumulation, where random mutations arising in cancer cells trigger corresponding specialised immune responses. Different from previous research, we explicitly model interactions between cancer and effector cells, while incorporating stochastic effects, which are especially important for the expansion and extinction of small populations. We find that the parameters governing interactions between the cancer and effector cells induce different outcomes of tumour progress, such as suppression and evasion. While it is hard to measure the cancer-immune dynamics directly in patients, genetic information of the cancer may indicate the presence of such interactions. Our model demonstrates signatures of selection in sequencing-derived summary statistics, such as the single-cell mutational burden. Thus, bulk and single-cell sequencing of a tumour may give information about the coevolutionary dynamics.
Eukaryotic initiation factors eIF4F and eIF4B promote translation termination upon closed-loop formation
Authors: Shuvalova Ekaterina , Shuvalov Alexey , Sheikh Walaa Al , Ivanov Alexander V. , Biziaev Nikita , Egorova Tatiana V. , Dmitriev Sergey E. , Terenin Ilya M. , Alkalaeva Elena 
Published: September 2024

ABSTRACTEukaryotic translation initiation factor eIF4F, comprising subunits eIF4G, eIF4E, and eIF4A, plays a pivotal role in the 48S preinitiation complex assembly and ribosomal scanning. Additionally, eIF4B enhances the helicase activity of eIF4A. eIF4F also interacts with PABP bound to the poly(A) tail of mRNA, thereby forming a closed-loop structure. PABP, in turn, interacts with eRF3, stimulating translation termination. Here, we employed a reconstituted mammalian system to directly demonstrate that eIF4F potently enhances translation termination. Specifically, eIF4A and eIF4B promote the loading of eRF1 into the A site of the ribosome, while eIF4G1 stimulates the GTPase activity of eRF3 and facilitates the dissociation of release factors following peptide release. We also identified MIF4G as the minimal domain required for this activity and show that eIF4G2/DAP5 can also promote termination. Our findings provide compelling evidence that the closed-loop mRNA structure facilitates translation termination, with PABP and eIF4F directly involved in this process.
Acute dietary methionine restriction highlights sensitivity of neocortex development to metabolic variations
Authors: Saha Sulov , Debacq Clémence , Audouard Christophe , Jungas Thomas , Dupre Pierrick , Fawal Mohamad-Ali , Chapat Clément , Michaud Henri-Alexandre , Le Cam Laurent , Lacroix Matthieu , Ohayon David , Davy Alice 
Published: September 2024

ABSTRACTMethionine -an essential amino acid that has to be provided by nutrition- and its metabolite S-Adenosyl methionine (SAM) are indispensable for cell proliferation, stem cell maintenance and epigenetic regulation1–5, three processes that are central to embryonic development6. Previous studies using chronic dietary restriction of methyl donors prior to and during gestation indicated that methionine restriction (MR) is detrimental to the development or growth of the neocortex7,8, however, the consequences of acute MR have not been extensively studied. Here, we designed a dietary MR regime coinciding with the neurogenic phases of neocortex development in the mouse. Our results indicate that dietary MR for 5 days leads to a severe reduction in neocortex growth and neuronal production. In comparison, growth of the liver and heart was unaffected, highlighting an organ-specific response to MR which was also observed at the cellular and molecular levels. Progenitor cohort labeling revealed a time-dependent sensitivity to MR and cell cycle analyses indicated that after 5 days of MR, progenitors are stalled in the S/G2 phases. Unexpectedly, neocortex growth reduction induced after 5 days of MR is completely rescued at birth when switching the dam back to control diet for the remaining of gestation, uncovering a mechanism of catch-up growth. Using multiplexed imaging we probed metabolic and epigenetic markers following MR and during catch-up growth and show that pyruvate metabolism is rewired in progenitors. Altogether, our data uncover a transient state of quiescence in G2/S which is metabolically distinct from G0 quiescence and associated with efficient catch-up growth. More globally, our study highlights both the extreme sensitivity of the developing neocortex to acute dietary changes and its remarkable plasticity.
Structural and biochemical characterization of the ALX4 dimer reveals novel insights into how disease alleles impact ALX4 function
Authors: Cain Brittany , Yuan Zhenyu , Thoman Evelyn , Kovall Rhett A. , Gebelein Brian 
Published: September 2024

1.AbstractHow homeodomain proteins gain sufficient DNA binding specificity to regulate diverse processes has been a long-standing question. Here, we determine how the ALX4 Paired-like protein achieves DNA binding specificity for a TAAT – NNN – ATTA dimer site. We first show that ALX4 binds this motif independently of its co-factor, TWIST1, in cranial neural crest cells. Structural analysis identified seven ALX4 residues that participate in dimer binding, many of which are conserved across the Paired-like family, but not other homeodomain proteins. Unexpectedly, the two ALX4 proteins within the dimer use distinct residues to form asymmetric protein-protein and protein-DNA interactions to mediate cooperativity. Moreover, we found that ALX4 cooperativity is required for transcriptional activation and that ALX4 disease variants cause distinct molecular defects that include loss of cooperativity. These findings provide new insights into how Paired-like factors gain DNA specificity and show how disease variants can be stratified based on their molecular defects.
Hypoxia and loss ofGCM1expression prevents differentiation and contact inhibition in human trophoblast stem cells
Authors: Cinkornpumin Jessica K. , Kwon Sin Young , Prandstetter Anna-Maria , Maxian Theresa , Sirois Jacinthe , Goldberg James , Zhang Joy , Saini Deepak , Dasgupta Purbasa , Jeyarajah Mariyan J. , Renaud Stephen J. , Paul Soumen , Haider Sandra , Pastor William A. 
Published: September 2024

AbstractThe placenta develops alongside the embryo and nurtures fetal development to term. During the first stages of embryonic development, due to low blood circulation, the blood and ambient oxygen supply is very low (∼1-2% O2) and gradually increases upon placental invasion. While a hypoxic environment is associated with stem cell self-renewal and proliferation, persistent hypoxia may have severe effects on differentiating cells and could be the underlying cause of placental disorders. We find that human trophoblast stem cells (hTSC) thrive in low oxygen, whereas differentiation of hTSC to trophoblast to syncytiotrophoblast (STB) and extravillous trophoblast (EVT) is negatively affected by hypoxic conditions. The pro-differentiation factor GCM1 (human Glial Cell Missing-1) is downregulated in low oxygen, and concordantly there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knockout of GCM1 in hTSC caused impaired EVT and STB formation and function, reduced expression of differentiation-responsive genes, and resulted in maintenance of self-renewal genes. Treatment with a PI3K inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation. Additionally, chromatin immunoprecipitation of GCM1 showed enrichment of GCM1-specific binding near key transcription factors upregulated upon differentiation including the contact inhibition factorCDKN1C.Loss ofGCM1resulted in downregulation ofCDKN1Cand corresponding loss of contact inhibition, implicating GCM1 in regulation of this critical process.
Neuroendocrine Control of Intestinal Regeneration Through the Vascular Niche inDrosophila
Authors: Medina André B. , Perochon Jessica , Johnson Cai , Polcowñuk Sofia , Tian Yuanliangzi , Yu Yachuan , Cordero Julia B. 
Published: September 2024

AbstractRobust and controlled intestinal regeneration is essential for the preservation of organismal health and wellbeing and involves reciprocal interactions between the intestinal epithelium and its microenvironment. While knowledge of regulatory roles of the microenvironment on the intestine is vast, how distinct perturbations within the intestinal epithelium may influence tailored responses from the microenvironment, remains understudied. Here, we present previously unknown signaling between enteroendocrine cells (EE), vasculature-like trachea (TTCs), and neurons, which drives regional and global stem cell proliferation during adult intestinal regeneration inDrosophila.Injury-induced ROS from midgut epithelial cells promotes the production and secretion of Dh31, the homolog of mammalian Calcitonin Gene-Related Peptide (CGRP), from anterior midgut EE cells. Dh31 from EE cells and neurons signal to Dh31 receptor within TTCs leading to cell autonomous production of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)-like Pvf1. Tracheal derived Pvf1 induces remodeling of the tracheal stem cell niche and regenerative ISC proliferation through autocrine and paracrine Pvr/MAPK signalling, respectively. Interestingly, while EE Dh31 exerts broad control of ISC proliferation throughout the midgut, functions of the neuronal source of the ligand appear restricted to the posterior midgut. Altogether, our work has led to the discovery of a novel enteroendocrine/neuronal/vascular signaling network controlling global and domain specific ISC proliferation during adult intestinal regeneration.
Optimized expansion microscopy reveals species-specific spindle microtubule organization inXenopusegg extracts
Authors: Guilloux Gabriel , Kitaoka Maiko , Mocaer Karel , Heichette Claire , Duchesne Laurence , Heald Rebecca , Pecot Thierry , Gibeaux Romain 
Published: September 2024

ABSTRACTThe spindle is a key structure in cell division as it orchestrates the accurate segregation of genetic material. While its assembly and function are well-studied, the mechanisms regulating spindle architecture remain elusive. In this study, we investigate the differences in spindle organization betweenXenopus laevisandXenopus tropicalis, leveraging expansion microscopy (ExM) to overcome the limitations of conventional imaging techniques. We optimized an ExM protocol tailored forXenopusegg extract spindles, improving upon fixation, denaturation and gelation methods to achieve higher resolution imaging of spindles. Our protocol preserves spindle integrity and allows effective pre-expansion immunofluorescence. This method enabled detailed analysis of the differences in microtubule organization between the two species.X. laevisspindles overall exhibited a broader range of bundle sizes, whileX. tropicalisspindles contained mostly smaller bundles. Moreover, while both species exhibited larger bundle sizes near and at the spindle center,X. tropicalisspindles otherwise consisted of very small bundles, andX. laevisspindles medium-sized bundles. By enhancing resolution and minimizing distortions and fixation artifacts, our optimized ExM approach offers new insights into spindle morphology and provides a robust tool for studying the structural intricacies of these large cellular assemblies. This work advances our understanding of spindle architecture and opens up new avenues for exploring underlying mechanisms.SIGNIFICANCE STATEMENTCorrect spindle morphology is key to its function; however, traditional microscopy methods limit our view of spindle architecture. This study addresses the gap in resolving detailed spindle microtubule organization by using advanced imaging.The research utilizes Expansion Microscopy (ExM) to reveal previously unobservable details of spindle morphology in egg extracts of twoXenopusspecies (X. laevisandX. tropicalis). This approach provides unprecedented clarity on microtubule arrangement and variations in spindle architecture.This work establishes a new protocol for high-resolution imaging of spindle structures, offering insights into how spindle architecture is adapted in differently-sized spindles to ensure proper function.