bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial and Ethnic Differences in White Matter Hyperintensity Burden: The Role of Vascular Risk Factors
Authors: Kamal Farooq , Moqadam Roqaie , Morrison Cassandra , Dadar Mahsa 
Published: December 2024

AbstractINTRODUCTIONWhite matter hyperintensities (WMHs) are markers of cerebrovascular pathology associated with cognitive decline. Reports of racial and ethnic differences in WMH have been inconsistent across studies. This study examined whether race and ethnicity influence WMH burden and whether vascular risk factors explain these differences.METHODSData from the National Alzheimer’s Coordinating Center included 7,132 Whites, 892 Blacks, 283 Asians, and 661 Hispanics. Baseline and longitudinal WMHs were examined using linear regression and mixed-effects models across racial and ethnic groups, controlling for demographics and vascular risk factors.RESULTSAdjusting for vascular risk factors reduced WMH burden differences and eliminated differences in temporal regions in Black vs White older adults. For Hispanics, differences became significant after adjusting for vascular risk factors.DISCUSSIONWhile some racial and ethnic WMH disparities are influenced by vascular risk factors, others persist, highlighting the need for multidimensional approaches when targeting WMHs in diverse populations.HighlightsCurrent research is inconsistent as to whether there are racial differences in WMHsBlacks exhibit higher WMH burden than Whites, mediated by vascular factorsIn Hispanics, WMH differences emerged only after adjusting for vascular risk factors
The economic value of vertebrate pollination in India
Authors: Kallivalappil Ratheesh , Cotter Sheena C. 
Published: December 2024

AbstractThe increasing urgency to understand the role and value of pollination in agriculture and plant conservation has elevated pollinators to a critical focus of research. While most crops—excluding cereals—are partially or entirely dependent on pollinators for fruit and seed production or benefit from improved yields due to their activities, the economic valuation of pollination services has primarily concentrated on insect pollinators globally and within India. However, comprehensive studies on the economic contributions of vertebrate pollinators in India remain absent. To address this gap, we evaluated the economic value of vertebrate pollination services for eight plant species by analyzing economic and production data from a published study. Using the methodologies of Klein et al. (2007), Gallai et al. (2009), and Gallai and Vaissiere (2009), we applied a contribution separation criterion to distinguish vertebrate pollination contributions from those of invertebrates. Our findings estimate the value of vertebrate pollination services at £2.86 million (D28.2 crore rupees), with bird pollinators contributing more than mammal pollinators. This study underscores the significant role of bat pollinators in supporting India’s economy and biodiversity through vital ecosystem services, highlighting their importance for conservation and policy initiatives.
Processes essential forPhyscomitrium patensprotonemal development require distinct levels of total activity provided by functionally redundant PpROP GTPases
Authors: Le Bail Aude , Kost Benedikt , Nüssel Janina , Lolis Tamara Isabeau , Koch David , Voll Hildegard , Schulmeister Sylwia , Ljung Karin , Ntefidou Maria 
Published: December 2024

AbstractRHO GTPases are key regulators of cellular and developmental processes in most eukaryotic organisms. ROPs (RHO of plants) constitute a plant-specific RHO subfamily. ROP families expanded and functionally diversified during the evolution of structurally complex vascular plants, but generally contain few members in non-vascular plants with ancient features. In vascular and non-vascular plants, ROP proteins are required for cell polarization, directional cell expansion, and mitotic cell plate positioning. All these processes are impaired by the disruption of PpROP activity in the non-vascular mossPhyscomitrium patens. The aim of the study presented here was to further characterize PpROP functions duringP. patensprotonemal development by a) knocking out individually or in all possible combinations each of the four RpROPgenes, which encode nearly identical proteins, b) complementing knock-out mutants with WT or mutant PpROP isoforms, or with heterologous homologs, and c) performing overexpression experiments. PpROPs were found to have additional previously unknown functions in the regulation of cell proliferation, caulonema differentiation, and gametophore formation. Furthermore, different cellular and developmental processes were shown to require distinct levels of total PpROP activity, rather than individual PpROP isoforms. Implications of the remarkable sequence conservation and functional integration within the PpROP protein family are discussed.One-sentence summaryKnock-out, complementation, and overexpression experiments further defined PpROP functions inP. patensdevelopment, and demonstrated their dependence on distinct levels of total PpROP activity.
Diagnostic accuracy of the STANDING algorithm in patients with isolated vertigo/dizziness, a multicentre prospective study (STANDING-M)
Authors: Ronchetti Mattia , Bartalucci Paola , Pepe Giuseppe , Canaroli Giulia , Magazzini Simone , de Curtis Ersilia , Di Sacco Federico , Bartolucci Maurizio , Pecci Rudi , Casula Claudia , Pelagatti Lorenzo , Fabiani Ginevra , Pavellini Andrea , Caviglioli Cosimo , Nazerian Peiman , Vannucchi Paolo , Vanni Simone 
Published: December 2024

ABSTRACTAimTo evaluate the diagnostic accuracy of the STANDING algorithm across different emergency departments (ED)s. As secondary outcomes we compared the STANDING and the local usual care (LUC), in term of accuracy, use of diagnostic resources and length of stay (LOS).MethodsWe prospectively enrolled adult patients presenting with vertigo/dizziness at one ‘hub’ and three ‘spoke’ EDs in Tuscany, evaluated using either STANDING or LUC depending on the availability of a trained emergency physician (EP). Imaging tests, consultations and discharge/admission decisions were made independently of the study. The reference standard was a diffusion-weighted MRI of the brain and 30-days follow-up.ResultsWe included 456 patients, 242 (53%) assessed by STANDING. No difference in age, gender and prevalence of cardiovascular risk factors were present between STANDING and LUC groups. The prevalence of central vertigo was 8.6%, with ischemic stroke (4.2%) as the leading cause, without differences between the two groups. The sensitivity, specificity, positive and negative predictive values (95% CI) of STANDING for central disease were 88.2% (63.6-98.5), 91.6% (87.1-94.8), 44.1% (33.2-55.7), 99% (96.5-99.7), without differences between the ‘hub’ and the ‘spoke’ centres and when only ischemic stroke was considered. STANDING demonstrated higher specificity and positive predictive values than that of LUC (36.5% and 14.7%, p<0.05 for both). Additionally, requests for head CT were lower (48.3% vs. 66.8%) and LOS shorter (289 vs. 351 minutes) in the STANDING group (p<0.05 for both).ConclusionsThe STANDING algorithm showed a good accuracy and a very high negative predictive value for excluding central disease and stroke, across different EDs. Compared to LUC, STANDING showed increased specificity, reduced utilisation of head CT and a shorter LOS.
Effects and dynamics of D-alanine in diabetes
Authors: Sakai Shinsuke , Okushima Hiroki , Iwata Yukimasa , Hayashi Terumasa , Takahara Shiro , Horio Masaru , Mita Masashi , Nakane Maiko , Kimura-Ohba Shihoko , Imamura Ryoichi , Kakuta Yoichi , Mizui Masayuki , Isaka Yoshitaka , Kimura Tomonori 
Published: December 2024

AbstractBackgroundD-alanine, a rare enantiomer of alanine, mediates renal gluconeogenesis and protects against viral infections by regulating the circadian clock’s transcriptional network. These features of D-alanine are associated with the diabetes, which disrupts circadian rhythm and worsens Covid-19 outcomes. This study examined the effects and dynamics of D-alanine in diabetic conditions.MethodsBlood and urine levels of D-alanine were measured in diabetic model mice and patients with diabetic kidney disease using a two-dimensional high-performance liquid chromatography system. Gluconeogenic activity of D-alanine was assessed by glucose production assay inex vivo-cultured kidney cells. Glucose tolerance test was performed in mice treated with D-alanine.ResultsThe circadian rhythm of D-alanine, present in healthy mice, was disrupted in diabetic model mice. Patients with diabetic kidney disease showed abnormal urinary excretion of D-alanine. In diabetic mice, D-alanine stimulated gluconeogenesis in kidneys. Although D-alanine treatment temporarily raised blood glucose levels, repetitive treatment of D-alanine did not worsen glucose tolerance in the tested conditions.ConclusionsAn abnormal circadian rhythm of D-alanine is a hallmark of diabetes. In diabetic mice, D-alanine affects kidney function without worsening the diabetic conditions. D-Alanine may provide a therapeutic option for diabetes by correcting circadian rhythms and treating viral infections.
Functional Ultrasound Imaging of Auditory Responses in Comatose Patients
Authors: Chen Zihao , Li Na , Xi Caihua , Zhu Jiejun , Wu Gang , Xia Jinzhao , Fei Chunlong , Sun Lei , Xu Hongzhi , Qiu Zhihai 
Published: December 2024

AbstractBedside monitoring of brain function in severely brain-injured patients remains a critical clinical challenge. We demonstrate the translational potential of functional ultrasound (fUS) imaging for this purpose. In two comatose patients (Glasgow Coma Scale ≤8) with cranial windows post-decompressive craniectomy, we used a 7.8 MHz transducer optimized for cortical depths of 1.5–4 cm to perform real-time fUS during auditory stimulation. We observed task-related increases in regional cerebral blood flow (rCBF) in relevant brain regions (P < 10^-3, t-test), which correlated with subsequent neurological recovery at nine-month follow-up. These findings establish fUS as a sensitive and portable tool for bedside brain function assessment, offering potential for improved prognostication, treatment guidance, and development of targeted rehabilitative strategies.
Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases
Authors: Stenton Sarah L. , Laricchia Kristen , Lake Nicole J. , Chaluvadi Sushma , Ganesh Vijay , DiTroia Stephanie , Osei-Owusu Ikeoluwa , Pais Lynn , O’Heir Emily , Austin-Tse Christina , O’Leary Melanie , Abu Shanap Mayada , Barrows Chelsea , Berger Seth , Bönnemann Carsten G. , Bujakowska Kinga M. , Campagna Dean R. , Compton Alison G. , Donkervoort Sandra , Fleming Mark D. , Gallacher Lyndon , Gleeson Joseph G. , Haliloglu Goknur , Pierce Eric A. , Place Emily M. , Sankaran Vijay G. , Shimamura Akiko , Stark Zornitza , Yang Tan Tiong , Thorburn David R. , White Susan M. ,   Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium, Vilain Eric , Lek Monkol , Rehm Heidi L. , O’Donnell-Luria Anne 
Published: December 2024

ABSTRACTBackgroundVariants in the mitochondrial genome (mtDNA) cause a diverse collection of mitochondrial diseases and have extensive phenotypic overlap with Mendelian diseases encoded on the nuclear genome. The mtDNA is often not specifically evaluated in patients with suspected Mendelian disease, resulting in overlooked diagnostic variants.MethodsUsing dedicated pipelines to address the technical challenges posed by the mtDNA - circular genome, variant heteroplasmy, and nuclear misalignment - single nucleotide variants, small indels, and large mtDNA deletions were called from exome and genome sequencing data, in addition to RNA-sequencing when available. A cohort of 6,660 rare disease families were analyzed (5,625 genetically undiagnosed, 84%) from the Genomics Research to Elucidate the Genetics of Rare diseases (GREGoR) Consortium as well as other rare disease cohorts.ResultsDiagnostic mtDNA variants were identified in 10 previously genetically undiagnosed families (one large deletion, eight reported pathogenic variants, one novel pathogenic variant). In one additional undiagnosed proband, the detection of >900 heteroplasmic variants provided functional evidence of pathogenicity to a novelde novovariant in the nuclear genePOLG(DNA polymerase gamma), responsible for mtDNA replication and repair.ConclusionmtDNA variant calling from data generated by exome and genome sequencing for nuclear variant analysis resulted in a genetic diagnosis or detection of a candidate variant for 0.4% of undiagnosed families affected by a broad range of rare diseases.
MEANtools: multi-omics integration towards metabolite anticipation and biosynthetic pathway prediction
Authors: Singh Kumar Saurabh , Suarez Duran Hernando , Del Pup Elena , Zafra-Delgado Olga , Van Wees Saskia C.M. , van der Hooft Justin J.J.i , Medema Marnix H. 
Published: December 2024

AbstractDuring evolution, plants have developed the ability to produce a vast array of specialized metabolites, which play crucial roles in helping plants adapt to different environmental niches. However, their biosynthetic pathways remain largely elusive. In the past decades, increasing numbers of plant biosynthetic pathways have been elucidated based on approaches utilizing genomics, transcriptomics, and metabolomics. These efforts, however, are limited by the fact that they typically adopt a target-based approach, requiring prior knowledge. Here, we present MEANtools, a systematic and unsupervised computational integrative omics workflow to predict candidate metabolic pathwaysde novoby leveraging knowledge of general reaction rules and metabolic structures stored in public databases. In our approach, possible connections between metabolites and transcripts that show correlated abundance across samples are identified using reaction rules linked to the transcript-encoded enzyme families. MEANtools thus assesses whether these reactions can connect transcript-correlated mass features within a candidate metabolic pathway. We validate MEANtools using a paired transcriptomic-metabolomic dataset recently generated to reconstruct the falcarindiol biosynthetic pathway in tomato. MEANtools correctly anticipated five out of seven steps of the characterized pathway and also identified other candidate pathways involved in specialized metabolism, which demonstrates its potential for hypothesis generation. Altogether, MEANtools represents a significant advancement to integrate multi-omics data for the elucidation of biochemical pathways in plants and beyond.
Impact of Proximal Tubule-Specific Deletion of Dipeptidyl Peptidase 4 on Blood Pressure, Renal Sodium Handling, and NHE3 Phosphorylation
Authors: Martins Flavia L. , Ribeiro-Silva Joao Carlos , Jesus Erika Fernandes de , Nistala Ravi , Girardi Adriana C. C. 
Published: December 2024

ABSTRACTDipeptidyl peptidase 4 (DPP4) is a transmembrane serine exopeptidase abundantly expressed in the kidneys, predominantly in the proximal tubule (PT); however, its non-enzymatic functions in this nephron segment remain poorly understood. While DPP4 physically associates with the Na+/H+exchanger isoform 3 (NHE3) and its inhibitors exert natriuretic effects, the DPP4 role in blood pressure (BP) regulation remains controversial. This study investigated the effects of PT-specificDpp4deletion (Dpp4ΔPT) and globalDpp4deletion (Dpp4−/−) on systolic blood pressure (SBP), natriuresis, and NHE3 regulation under baseline and angiotensin II (Ang II)-stimulated conditions in both male and female mice. Global and PT-specificDpp4deletion increased diuretic and natriuretic responses to acute saline loading, correlating with enhanced phosphorylation of NHE3 at serine 552 (pS552-NHE3). However, baseline SBP remained unchanged. Ang II stimulation increased DPP4 activity in control mice, with a greater effect in males than in females, reflecting sex-dependent regulation of renal DPP4. InDpp4ΔPTmice, residual kidney DPP4 was unresponsive to Ang II, indicating that PT DPP4, rather than DPP4 in other nephron segments, is regulated by Ang II. Ang II administration increased SBP in all groups; however, the pressor response was significantly attenuated in bothDpp4ΔPTandDpp4−/−mice, coinciding with sustained elevated levels of pS552-NHE3. Collectively, these findings demonstrate that PT DPP4 modulates NHE3 activity through mechanisms that prevent the accumulation of pS552-NHE3, exerting an anti-natriuretic effect. In the absence of DPP4, these mechanisms are disrupted, reducing Ang II sensitivity and maintaining high pS552-NHE3 levels, underscoring the role of DPP4 in PT signaling and function.
Interferon-β induction heterogeneity during KSHV infection is determined by interferon-β enhanceosome transcription factors other than IRF3
Authors: Kaku Machika , Gaglia Marta Maria 
Published: December 2024

AbstractStrict regulation of type I interferons (IFN) is vital for balancing tissue damage and immunity against infections. We previously found that during Kaposi’s sarcoma-associated herpesvirus infection, IFN induction was limited to a small percentage of infected B cells. This heterogeneity was not explained by viral gene expression. Here, we used a fluorescent reporter and fluorescence-activated cell sorting to investigate the source of this heterogeneity. Surprisingly, the canonical IFN induction pathway culminating in the activation of the IRF3 transcription factor was similar between cells that made high vs. low/no IFN-β. In contrast, the activation or expression of two other IFN transcription factors, NF-κB and AP-1, correlated with heterogeneous IFN-β induction. Our results suggest that at the level of individual cells, IRF3 is crucial as a pathogen detection signal, but NF-κB and AP-1 are limiting for IFN-β induction.
Safety and efficacy of bronchus-blocked ultrasound-guided percutaneous transthoracic needle biopsy (BUS-PTNB) for critically ill patients under invasive mechanical ventilation: a prospective, single-arm trial
Authors: Yu He , Liu Yun , Wang Zhen , Sun Peng , Wang Weiya , Xia Wenxi , Qi Wenli , Wu Linfei , Liu Guangdi , Zhou Yaxiong , Yao Rong , Zhao Yuean , Liu Siyu , Lin Xue , He Qian , Liang Zuoyu , Yin Wanhong , Zhou Ran , Mi Yiqun , Luo Jianjiang , Zhou Hui , Long Huaicong , Luo Zhuang , Fan Junping , Powell Charles A. , Liang Zongan , Wang Ye 
Published: December 2024

AbstractObjectivesConventional lung biopsy for critically ill patients who under invasive mechanical ventilation (IMV) is limited due to high risks of procedure-related complications. We developed a novel technique named bronchus-blocked ultrasound-guided percutaneous transthoracic needle biopsy (BUS-PTNB) to mitigate the risks of biopsy under IMV, but its safety and efficacy have not been prospectively evaluated.MethodsIn this prospective, single-arm trial (Chictr.org, ChiCTR2100054047), invasively ventilated patients with undiagnosed lung opacities were screened and underwent BUS-PTNB after enrollment. The peri-operative conditions, severity of complications, pathological findings, and tissue-based metagenomic next-generation sequencing (mNGS) results were systemically evaluated.ResultsA total of 22 critically ill patients (18 men, mean age, 64.2 years [SD 11.7], APACHE II score, 27.0 [SD 5.6], PaO2/FiO2ratio, 120.5 [IQR 91.9–169.1]) under IMV were enrolled in the study. Throughout the procedure, there were no significant changes in respiratory rate or PaO2. Biopsy-related complications occurred in 3 patients (13.6%), including pneumothorax (n=1, 4.5%), intrabronchial hemorrhage (n=2, 9.1%), and hemothorax (n=3, 13.6%). Notably, one patient (P10) required a blood transfusion due to hemothorax, which was classified as a severe complication (1/22, 4.5%). Satisfactory biopsy samples were obtained from 21 patients (95.5%) for pathological study and from all 22 patients (100%) for mNGS.ConclusionsThe novelBUS-PTNB is a promising bedside biopsy technique for ICU patients under IMV with acceptable complication risk. This technique may prove instrumental in advancing pathological studies of severe lung diseases.Key points and Clinical Relevance StatementQuestionWe developed bronchus-blocked ultrasound-guided percutaneous transthoracic needle biopsy (BUS-PTNB) for patients under invasive mechanical ventilation, but its safety and efficacy have not been prospectively evaluated.FindingsPatients’ vital signs showed no significant fluctuations. Biopsy-related complications occurred in 3 patients out of 22. Satisfactory samples were obtained for pathological study and mNGS.Clinical RelevanceBUS-PTNB is a promising bedside biopsy technique for ICU patients under IMV with acceptable complication risk. This technique may prove instrumental in advancing pathological studies of severe lung diseases.
Predictors of glycemic control, quality of life and diabetes self-management of patients with diabetes mellitus at a tertiary hospital in Ghana
Authors: Gyan Kwadwo Faka , Agyenim-Boateng Enoch , Hutton-Mensah Kojo Awotwi , Opare-Addo Priscilla Abrafi , Gyabaah Solomon , Ofori Emmanuel , Asamoah Osei Yaw , Naabo Mohammed Najeeb , Owiredu Michael Asiedu , Tannor Elliot Koranteng 
Published: December 2024

AbstractBackgroundThe burden of diabetes mellitus (DM) in Sub-Saharan Africa is high and continues to increase. Effective DM management focuses on key goals such as glycemic control, prevention of acute and chronic complications and improvement of quality of life (QOL). This study therefore assessed predictors of glycemic control, QOL and diabetes self-management (DSM) of patients with DM in a tertiary hospital in Ghana.MethodsWe conducted a cross-sectional study involving face-to-face interviews of patients with DM attending clinic using structured questionnaires and validated study instruments as well as review of medical records. A multivariable logistics regression analysis was used to identify independent factors associated with good glycemic control, poor QOL and poor DSM practices.ResultsThe study involved 360 patients with mean age of 62.5 ± 11.6 years and a female preponderance, 271 (75.3%). The mean HbA1c among study participants was 7.8 ± 2.7% of which 44.7% had HbA1C <7%. Patients on only oral DM medications (aOR 2.14; 95% CI 1.19-3.88, p=0.012) were more likely to have good glycemic control. Urban residence (aOR 0.24; 95% CI 0.06-0.87, p=0.030) and good DSM (aOR 0.05; 95% CI 0.02-0.13, p<0.001) were protective of having poor QOL however, recent hospitalization (within the past 3 months) (aOR 4.58; 95 % CI 1.58-13.26, p=0.005) had higher odds of poor quality of life. Patients who were divorced (aOR 6.79; 95% CI 1.20-40.42, p=0.030) had higher odds of poor DSM, while having attended the clinic for more than 3 years (aOR 0.32; 95% CI 0.12-0.81, p=0.016) was protective of poor DSM.ConclusionGood social support and sustained DSM interventions result in good DSM and ultimately improves quality of life of patients with DM.