bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline Lung Allograft Dysfunction After Bilateral Lung Transplantation Is Associated With an Increased Risk of Death: Results From a Multicenter Cohort Study
Authors: Keller Michael B. , Sun Junfeng , Alnababteh Muhtadi , Ponor Lucia , D. Shah Pali , Mathew Joby , Kong Hyesik , Charya Ananth , Luikart Helen , Aryal Shambhu , Nathan Steven D. , Orens Jonathan B. , Khush Kiran K. , Kyoo Jang Moon , Agbor-Enoh Sean 
Published: June 2024

Background.
A prior single-center, retrospective cohort study identified baseline lung allograft dysfunction (BLAD) as a risk factor for death in bilateral lung transplant recipients. In this multicenter prospective cohort study, we test the association of BLAD with death in bilateral lung transplant recipients, identify clinical risk factors for BLAD, and assess its association with allograft injury on the molecular level.

Methods.
This multicenter, prospective cohort study included 173 bilateral lung transplant recipients that underwent serial pulmonary function testing and plasma collection for donor-derived cell-free DNA at prespecified time points. BLAD was defined as failure to achieve ≥80% predicted for both forced expiratory volume in 1 s and forced vital capacity after lung transplant, on 2 consecutive measurements at least 3 mo apart.

Results.
BLAD was associated with increased risk of death (hazard ratio, 1.97; 95% confidence interval [CI], 1.05-3.69; P = 0.03) but not chronic lung allograft dysfunction alone (hazard ratio, 1.60; 95% CI, 0.87-2.95; P = 0.13). Recipient obesity (odds ratio, 1.69; 95% CI, 1.15-2.80; P = 0.04) and donor age (odds ratio, 1.03; 95% CI, 1.02-1.05; P = 0.004) increased the risk of developing BLAD. Patients with BLAD did not demonstrate higher log10(donor-derived cell-free DNA) levels compared with no BLAD (slope [SE]: –0.0095 [0.0007] versus –0.0109 [0.0007]; P = 0.15).

Conclusions.
BLAD is associated with an increased risk of death following lung transplantation, representing an important posttransplant outcome with valuable prognostic significance; however, early allograft specific injury on the molecular level does not increase the risk of BLAD, supporting further mechanistic insight into disease pathophysiology.
Actin isovariant ACT2-mediated cellular auxin homeostasis regulates lateral root organogenesis inArabidopsis thaliana
Authors: Hanzawa Aya , Rahman Arifa Ahamed , Rahman Abidur 
Published: June 2024

AbstractLateral root (LR) organogenesis is regulated by cellular flux of auxin within pericycle cells, which depends on the membrane distribution and polar localization of auxin carrier proteins. The correct distribution of auxin carrier proteins relies on the intracellular trafficking of these proteins aided by filamentous actin as a track. However, the precise role of actin in lateral root development is still elusive. Here, using vegetative class actin isovariant mutants, we revealed that loss of actin isovariant ACT8 led to an increase in lateral root formation. The distribution of auxin within pericycle cells was altered inact8mutant, primarily due to the altered distribution of AUX1 and PIN7. Interestingly, incorporation ofact2mutant inact8background (act2act8) effectively nullified the LR phenotype observed inact8mutant, indicating that ACT2 plays an important role in LR development. To explore further, we investigated the possibility that theact8mutant’s LR phenotype and cellular auxin distribution resulted from ACT2 overexpression. Consistent with the idea, enhanced lateral root formation, altered AUX1, PIN7 expression and auxin distribution in pericycle cells were observed in ACT2 overexpression lines. Collectively, these results suggest that actin isovariant ACT2 but not ACT8 plays a pivotal role in regulating source to sink auxin distribution during lateral root organogenesis.
Spectrally Resolved Single Molecule Orientation Imaging Reveals Direct Correspondence between Polarity and Order Experienced by Nile Red in Supported Lipid Bilayer Membrane
Authors: Sarkar Aranyak , Mitra Jyotsna Bhatt , Sharma Veerendra K. , Namboodiri Vinu , Kumbhakar Manoj 
Published: June 2024

ABSTRACTMolecular level interaction among lipids, cholesterol and water dictates nanoscale membrane organization of lipid bilayers into liquid ordered (Lo) and liquid disordered (Ld) phases, characterized by different polarity and order. Generally, solvatochromic dyes easily discriminate polarity difference between Lo and Ld phases, whereas molecular flippers and rotors show distinct photophysics depending on membrane order. In spite of progress in single molecule spectral imaging and single molecule orientation mapping, still direct experimental proof linking polarity with order sensed by the same probe eludes us. Here, we demonstrate spectrally resolved single molecule orientation localization microscopy to connect nanoscopic localization of probe on bilayer membrane with its emission spectra, three-dimensional dipole orientation and rotational constraint offered by the local microenvironment and highlights the beautiful correspondence between polarity and order. This technique has the potential to addres nanoscale heterogeneity and dynamics, especially in biology as well as material sciences.TOC GRAPHICS
Localization of Proteins Involved in the Biogenesis of the Photosynthetic Apparatus to Thylakoid Subdomains in Arabidopsis
Authors: Chotewutmontri Prakitchai , Barkan Alice 
Published: June 2024

AbstractThylakoid membranes in chloroplasts and cyanobacteria harbor the multisubunit protein complexes that catalyze the light reactions of photosynthesis. In plant chloroplasts, the thylakoid membrane system comprises a highly organized network with several subcompartments that differ in composition and morphology: grana stacks, unstacked stromal lamellae, and grana margins at the interface between stacked and unstacked regions. The localization of components of the photosynthetic apparatus among these subcompartments has been well characterized. However, less is known about the localization of proteins involved in the biogenesis and repair of the photosynthetic apparatus, the partitioning of proteins between two recently resolved components of the traditional margin fraction (refined margins and curvature), and the effects of light on these features. In this study, we analyzed the partitioning of numerous thylakoid biogenesis and repair factors among grana, curvature, refined margin, and stromal lamellae fractions of Arabidopsis thylakoid membranes, comparing the results from illuminated and dark-adapted plants. Several proteins previously shown to localize to a margin fraction partitioned in varying ways among the resolved curvature and refined margin fractions. For example, the ALB3 insertase and FtsH protease involved in photosystem II (PSII) repair were concentrated in the refined margin fraction, whereas TAT translocon subunits and proteins involved in early steps in photosystem assembly were concentrated in the curvature fraction. By contrast, two photosystem assembly factors that facilitate late assembly steps were depleted from the curvature fraction. The enrichment of the PSII subunit OE23/PsbP in the curvature fraction set it apart from other PSII subunits, supporting the previous conjecture that OE23/PsbP assists in PSII biogenesis and/or repair. The PSII assembly factor PAM68 partitioned differently among thylakoid fractions from dark-adapted plants and illuminated plants, and was the only analyzed protein to convincingly do so. These results demonstrate an unanticipated spatial heterogeneity of photosystem biogenesis and repair functions in thylakoid membranes, and reveal the curvature fraction to be a focal point of early photosystem biogenesis.
Use of the EsoGuard®Molecular Biomarker Test in Non-Endoscopic Detection of Barrett’s Esophagus among High-Risk Individuals in a Screening Population
Authors: Shaheen Nicholas J. , Othman Mohamed O. , Taunk Jawar , Chang Kenneth J. , Jaganmohan Sathya , Yachimski Patrick S. , Fang John C. , Spataro Joseph S. , Verma Suman , Lee Victoria T. , deGuzman Brian J. , Aklog Lishan 
Published: June 2024

AbstractBackground and AimsBarrett’s Esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). We aimed to assess performance, safety, and tolerability of the EsoGuard (EG) assay on samples collected non-endoscopically with the EsoCheck (EC) device (EG/EC) for BE detection in the intended-use population, meeting American College of Gastroenterology (ACG) guideline criteria (chronic gastroesophageal reflux disease (GERD) and 3+ additional risk factors).MethodsWe performed a prospective, multicenter study (NCT04293458) to assess EG performance (primary endpoint) on cells collected with EC, for detection of BE and EAC using esophagogastroduodenoscopy (EGD) and biopsies as the comparator. Twenty-four sites across the U.S. and Spain participated. EC safety and usability were assessed as secondary endpoints.Results180 male subjects aged >50 years with chronic GERD met eligibility criteria, of which 163 (90.6%) had EGD and successful EC administration. Mean age was 60.5yrs, 34.4% were obese, 56.7% had tobacco history, and 3.9% had a 1stdegree relative with BE or EAC. Of 122 samples analyzed, 93 contributed to the primary endpoint analysis. About 9% of subjects in the Primary Analysis Population had BE on EGD, none with dysplasia. Sensitivity of EG for BE was 87.5% (95% CI 47.4-99.7), specificity was 81.2% (95% CI 71.2-88.8), positive predictive value was 30.4% (95% CI 13.2-52.9), and negative predictive value was 98.6% (95% CI 92.3-99.96). Mild esophageal abrasions were observed in 1.5%; no serious adverse events were reported.ConclusionsEG/EC appears effective for BE screening. This approach provides a safe, accurate, and well-tolerated non-endoscopic alternative in high-risk patients.
Cognitive Outcomes of the At-Home Brain Balance Program
Authors: Jackson Rebecca , Meng Yue 
Published: June 2024

AbstractAccessibility to developmental interventions for children and adolescents could be increased through virtual, at-home delivery of home-based training programs incorporating technology. Virtual childhood training programs and their effects on cognitive outcomes in children and adolescents with developmental delays have not been well studied. To that end, this study examined the effects of the virtual at-home Brain Balance®(BB) program on the cognitive task performance of children and adolescents with baseline developmental and attentional difficulties (aged 4-17 years). The at-home BB program is delivered through: (1) a computer-based format utilizing multimodal program activities previously studied in-center (multisensory stimulation with gross motor, coordination, balance, and timing activities, along with nutritional recommendations); and (2) the BB app (visual motor, auditory and visual processing, and rhythm and timing training) — creating a comprehensive program experience delivered remotely. Cognitive performance was measured by six online cognitive assessments from Creyos Health before and after 3 months of participation in the at-home BB program (N = 316) or in-center BB program (N = 4,232), compared to controls. Results showed that overall cognitive assessment scores (including attention, response inhibition, and working memory) improved after participation in either the at-home or the in-center program, compared to controls. Importantly, significant improvements over the controls were observed for two tasks, Double Trouble and Feature Match, in both programs. Further, two analyses support that the effects on cognitive performance from either delivery format, in-center or at home, are comparable in magnitude. This research: (1) presents new findings demonstrating improved cognitive performance after 3 months of the at-home BB program; (2) replicates previous findings of cognitive improvements after 3 months of the in-center BB program; and (3) suggests that the cognitive effects of virtual at-home BB training are similar to those observed for in-center BB training. Overall, the results demonstrate the effectiveness of the at-home BB program in improving cognitive functioning in pediatric populations with preexisting developmental and attentional difficulties. With virtual delivery and ease of use, at-home programs have the potential to increase access to much-needed developmental and cognitive support, ultimately reaching populations that may otherwise lack easy access to high-quality, evidence-based developmental programs.
Unveiling the Longitudinal Journey: Three-Year Follow-up of Women with MINOCA and INOCA in a Specialized Heart Centre
Authors: Théberge Emilie T. , Burden Elizabeth , Leung Katrina , Parvand Mahraz , Prodan-Bhalla Natasha , Humphries Karin H. , Sedlak Tara L. 
Published: June 2024

AbstractBackgroundMyocardial infarction with no obstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), are female predominant conditions, with a lack of clinical trials guiding medical management for the common underlying vasomotor etiologies. Long-term outcomes of (M)INOCA patients following attendance at a women’s heart center (WHC) are lacking.MethodsWomen diagnosed with MINOCA (n=51) or INOCA (n=112) were prospectively followed for 3 years at the Vancouver WHC. Baseline characteristics, diagnoses, chest pain type, major adverse cardiac events, hospital encounters, medications, and Seattle Angina Questionnaire (SAQ) responses were compared between baseline and 3 years. Chi-squared tests were used to compare categorical variables, with Students’ t-tests for continuous variables.ResultsMINOCA patients had significantly more non-exertional chest pain and diagnoses of vasospasm than INOCA patients, who had more exertional chest pain and diagnoses of coronary microvascular dysfunction. Following baseline, both groups had significant reductions in cardiovascular emergency room visits, with INOCA patients also experiencing fewer cardiovascular hospitalizations. At 3 years, the most commonly prescribed medications were calcium channel blockers, long-acting nitrates and beta blockers, with MINOCA having more acetylsalicylic acid and INOCA more short-acting nitrates and ranolazine prescriptions. Both groups observed significant improvements in SAQ scores, with greater improvements observed in INOCA patients. Patients with depression or prescribed ranolazine at 3 years had worse SAQ scores at baseline.ConclusionsThree-year outcomes of (M)INOCA patients indicate that the WHC’s comprehensive care model effectively improves diagnostic clarity, reduces hospital encounters, optimizes medication management, and improves self-reported patient well-being.
Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans
Authors: Darcey Valerie L. , Guo Juen , Chi Meible , Chung Stephanie T. , Courville Amber B. , Gallagher Isabelle , Herscovitch Peter , Joseph Paule V. , Howard Rebecca , LaNoire Melissa , Milley Lauren , Schick Alex , Stagliano Michael , Turner Sara , Urbanski Nicholas , Yang Shanna , Zhai Nan , Zhou Megan S. , Hall Kevin D. 
Published: June 2024

ABSTRACTUltra-processed foods high in fat and sugar may be addictive, in part, due to their purported ability to induce an exaggerated postingestive brain dopamine response akin to drugs of abuse. Using standard [11C]raclopride positron emission tomography (PET) displacement methods used to measure brain dopamine responses to addictive drugs, we measured postingestive striatal dopamine responses to an ultra-processed milkshake high in fat and sugar in 50 young, healthy adults over a wide body mass index range (BMI 20-45 kg/m2). Surprisingly, milkshake consumption did not result in significant postingestive dopamine response in the striatum (p=0.62) nor any striatal subregion (p>0.33) and the highly variable interindividual responses were not significantly related to adiposity (BMI:r=0.076,p=0.51; %body fat:r=0.16,p=0.28). Thus, postingestive striatal dopamine responses to an ultra-processed milkshake were likely substantially smaller than many addictive drugs and below the limits of detection using standard PET methods.ClinicalTrials.gov Identifier:NCT03648892
Tolerant mothers: aggression does not explain solitary living in the bush Karoo rat
Authors: Makuya L. , Pillay N. , Sangweni S.P. , Schradin C. 
Published: June 2024

AbstractMany mammal species are thought to adopt solitary living due to mothers becoming intolerant of their adult offspring as well as social intolerance between adults. However, field studies on how solitary mammals interact are rare. Here we show that solitary living can occur without social intolerance. Over three years, we recorded interactions between free living bush Karoo rats (Otomys unisulcatus) and conducted dyadic encounter experiments between kin and non-kin female neighbours, both in a neutral test arena and in field intruder experiments. Social interactions were rare (N=230 in N=2062 observations), and, when observed, were aggressive in only 34% of the cases. In dyadic encounters, mothers interacted amicably with young offspring. Aggression between mothers and offspring was almost absent. This mother-offspring relationship remained amicable even after the offspring had dispersed. Aggression between neighbouring adult females was low in neutral arena tests, independent of kinship and season. However, in the field, females reacted more aggressively towards non-kin than kin intruders, especially during the breeding season. Tolerance between mothers and adult offspring indicates that aggression is not the mechanism leading to natal dispersal and solitary living. We found a solitary social system characterised by social tolerance, suggesting that dispersal in combination with a lack of social attraction rather than aggression can lead to solitary living.
Integration of ATAC and RNA-sequencing identifies chromatin and transcriptomic signatures in classical and non-classical zebrafish osteoblasts and indicates mechanisms ofentpd5aregulation
Authors: Petratou Kleio , Stehling Martin , Müller Ferenc , Schulte-Merker Stefan 
Published: June 2024

AbstractTwo types of osteoblasts are required to assemble the zebrafish embryonic skeleton: classical osteoblasts homologous to the mammalian cell, and notochord sheath cells, which serve as non-classical osteoblasts. The geneentpd5ais critically required for ossification via both types of osteoblasts. Despite the indispensability of zebrafish models in vertebrate research, the genetic regulation of bone formation, as well as mechanisms of transcriptional control ofentpd5a, remain largely unknown. Here, using a newly generated transgenic line, we isolate classical and non-classical osteoblasts from zebrafish embryos and performed both ATAC-seq and RNA-seq. We analysed results independently and integratively to understand those chromatin dynamics and accompanying transcriptomic changes that occur in different skeletal cell types. We show that although Dlx family factors are playing important roles in classical osteoblast regulation, Hox family factors are involved in governing spinal ossification via non-classical osteoblasts. We further present a resource-driven analysis of theentpd5apromoter, experimentally validating the ATAC-seq dataset and proposing mechanisms of regulating the complexentpd5aexpression pattern during zebrafish osteogenesis. Our results thus provide a necessary comprehensive resource for the field of bone development and indicate spatio-temporally regulated promoter/enhancer interactions taking place in theentpd5alocus.
Sex-steroid hormones relate to cerebellar structure and functional connectivity across adulthood
Authors: Magalhães Thamires N. C. , Hicks Tracey H. , Jackson T. Bryan , Ballard Hannah K. , Herrejon Ivan A. , Bernard Jessica A. 
Published: June 2024

AbstractAging involves complex biological changes that affect disease susceptibility and aging trajectories. Although females typically live longer than males, they have a higher susceptibility to diseases like Alzheimer’s, speculated to be influenced by menopause, and reduced ovarian hormone production. Understanding sex-specific differences is crucial for personalized medical interventions and gender equality in health. Our study aims to elucidate sex differences in regional cerebellar structure and connectivity during normal aging by investigating both structural and functional connectivity variations, with a focus on investigating these differences in the context of sex-steroid hormones. The study included 138 participants (mean age = 57(13.3) years, age range = 35-86 years, 54% women). The cohort was divided into three groups: 38 early middle-aged individuals (EMA) (mean age = 41(4.7) years), 48 late middle-aged individuals (LMA) (mean age = 58(4) years), and 42 older adults (OA) (mean age = 72(6.3) years). All participants underwent MRI scans, and saliva samples were collected for sex-steroid hormone quantification (17β-estradiol (E), progesterone (P), and testosterone (T)). We found less connectivity in females between Lobule I-IV and the cuneus, and greater connectivity in females between Crus I, Crus II, and the precuneus with increased age. Higher 17β-estradiol levels were linked to greater connectivity in Crus I and Crus II cerebellar subregions. Analyzing all participants together, testosterone was associated with both higher and lower connectivity in Lobule I-IV and Crus I, respectively, while higher progesterone levels were linked to lower connectivity in females. Structural differences were observed, with EMA males having larger volumes compared to LMA and OA groups, particularly in the right I-IV, right Crus I, right V, and right VI. EMA females showed higher volumes in the right lobules V and VI. These results highlight the significant role of sex hormones in modulating cerebellar connectivity and structure across adulthood, emphasizing the need to consider sex and hormonal status in neuroimaging studies to better understand age-related cognitive decline and neurological disorders.
Single-nucleus RNA sequencing reveals enduring signatures of acute stress and chronic exercise in striatal microglia
Authors: Connolly Meghan G. , Johnson Zachary V. , Chu Lynna , Johnson Nicholas D. , Buhr Trevor J. , McNeill Elizabeth M. , Clark Peter J. , Rhodes Justin S. 
Published: June 2024

AbstractAcute stress has enduring effects on the brain and motivated behavior across species. For example, acute stress produces persisting decreases in voluntary physical activity as well as molecular changes in the striatum, a brain region that regulates voluntary physical activity and other motivated behaviors. Microglia, the primary immune cells of the central nervous system, are positioned at the interface between neural responses to stress and neural coordination of voluntary activity in that they respond to stress, sense molecular changes in the striatum, and modulate neuronal activity. However, the role of striatal microglia in stress-induced long-term suppression of voluntary activity is unknown. Here we employ single nucleus RNA-sequencing to investigate how stress and exercise impact the biology of microglia in the striatum. We find that striatal microglia display altered activation profiles six weeks after an acute stressor. Furthermore, we show that access to a running wheel is associated with an additional and distinct microglial activation profile characterized by upregulation of genes related to complement components and phagocytosis pathways. Lastly, we find that distinct gene sets show expression changes associated with general access to a running wheel versus variation in running levels. Taken together, our results deepen our understanding of the diverse molecular states that striatal microglia assume in response to stress and exercise and suggest that microglia exhibit a broader range of functional states than previously thought.