bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunologic Benefits of 0-antigen Mismatched Transplants: No Added Boost for Racial and Ethnic Minorities
Authors: Caldwell Jillian S. , Parvathinathan Gomathy , Stedman Margaret R. , Ahearn Patrick , Tan Jane C. , Cheng Xingxing S. 
Published: June 2024

Background.
Systemic barriers to posttransplant care, including access to immunosuppressant medications, contribute to higher rates of kidney transplant failure in racial minorities. Matching donor and recipient HLA alleles reduce allorecognition, easing reliance on immunosuppression. We hypothesize that 0-antigen mismatch transplants may provide stronger protection against graft loss in racial minorities.

Methods.
We compared adult, single-organ, deceased-donor kidney transplants in the United States from 2007 to 2016 by degree of HLA mismatch (0- versus ≥1-antigen mismatch). We examined time-to-allograft failure, with death as a competing event, using multivariable Weibull models, stratified by recipient race (White versus non-White), and evaluated the interaction between mismatch and recipient race. We used Kaplan-Meier imputation to account for competing risk of death.

Results.
We analyzed 102 114 transplants (median follow-up, 5.6 y; 16 862 graft losses, 18 994 deaths). Zero-antigen mismatch was associated with improved allograft survival (adjusted subdistribution hazard ratio [sHR] 0.80; 95% confidence interval [CI], 0.75-0.85). When stratified by recipient race, the effect of 0-antigen mismatch was more pronounced in White (unadjusted sHR 0.78; 95% CI, 0.72-0.83) versus non-White recipients (sHR 0.88; 95% CI, 0.79-0.99; interaction P = 0.04). The differential effect was attenuated after adjusting for covariates (sHR 0.78; 95% CI, 0.73-0.84 versus sHR 0.87; 95% CI, 0.77-0.98; interaction P = 0.10).

Conclusions.
Zero-antigen mismatch transplants conferred a 20% risk reduction in allograft loss, which was similar between non-White and White recipients. This may reflect an increased degree of mismatch at other HLA alleles and non-HLA alleles in non-White recipients or because of the extent of systemic barriers to healthcare borne by minority recipients.
Exploring Preservation Modalities in a Split Human Pancreas Model to Investigate the Effect on the Islet Isolation Outcomes
Authors: Buemi Antoine , Mourad Nizar I. , Bouzin Caroline , Devresse Arnaud , Hoton Delphine , Daumerie Aurelie , Zech Francis , Darius Tom , Kanaan Nada , Gianello Pierre , Mourad Michel 
Published: June 2024

Background.
In islet transplantation, the use of dynamic hypothermic preservation techniques is a current challenge. This study compares the efficacy of 3 pancreas preservation methods: static cold storage, hypothermic machine perfusion (HMP), and oxygenated HMP.

Methods.
A standardized human pancreas split model was employed using discarded organs from both donation after brain death (n = 15) and donation after circulatory death (DCD) (n = 9) donors. The pancreas head was preserved using static cold storage (control group), whereas the tail was preserved using the 3 different methods (study group). Data on donor characteristics, pancreas histology, isolation outcomes, and functional tests of isolated islets were collected.

Results.
Insulin secretory function evaluated by calculating stimulation indices and total amount of secreted insulin during high glucose stimulation (area under the curve) through dynamic perifusion experiments was similar across all paired groups from both DCD and donation after brain death donors. In our hands, islet yield (IEQ/g) from the pancreas tails used as study groups was higher than that of the pancreas heads as expected although this difference did not always reach statistical significance because of great variability probably due to suboptimal quality of organs released for research purposes. Moreover, islets from DCD organs had greater purity than controls (P ≤ 0.01) in the HMP study group. Furthermore, our investigation revealed no significant differences in pancreas histology, oxidative stress markers, and apoptosis indicators.

Conclusions.
For the first time, a comparative analysis was conducted, using a split model, to assess the effects of various preservation methods on islets derived from pancreas donors. Nevertheless, no discernible variances were observed in terms of islet functionality, histological attributes, or isolation efficacy. Further investigations are needed to validate these findings for clinical application.
Roseateles subflavus sp. nov. and Roseateles aquae sp. nov., isolated from artificial pond water and Roseateles violae sp. nov., isolated from a Viola mandshurica root
Authors: Woo Haejin , Chhetri Geeta , Kim Inhyup , So Yoonseop , Park Sunho , Jung Yonghee , Seo Taegun 
Published: June 2024

Two novel strains, designated APW6T and APW11T, were isolated from artificial pond water, and one novel strain, designated PFR6T, was isolated from a Viola mandshurica root. These strains were found to be Gram-negative, rod-shaped, motile by means of flagella, and oxidase-positive. Growth conditions of the type strains were as follows: APW6T, 15–43 °C (optimum, 28 °C), pH 6.0–12.0 (optimum, pH 7.0), with no salinity; APW11T, 4–35 °C (optimum, 25 °C), pH 6.0–11.0 (optimum, pH 9.0), with 0–1 % NaCl (w/v, optimum 0 %); PFR6T, 10–38 °C (optimum 28 °C), pH 6.0–12.0 (optimum, pH 7.0), with 0–2 % NaCl (w/v; optimum, 0 %). Strains APW6T, APW11T, and PFR6T belonged to the genus Roseateles, having the most 16S rRNA gene sequence similarity to Roseateles saccharophilus DSM 654T (98.1 %), Roseateles oligotrophus CHU3T (98.7 %), and Roseateles puraquae CCUG 52769T (98.1 %). The estimated genome sizes of APW6T, APW11T, and PFR6T were 50 50 473, 56 70 008, and 52 16 869 bp, respectively and the G+C contents were 69.5, 66, and 68.5 mol%. The digital DNA–DNA hybridization, average amino acid identity, and average nucleotide identity values among the novel strains and related taxa were all lower than 22.4, 74.7, and 78.9 %, respectively. The predominant cellular fatty acids (>10 %) of all strains were summed feature 3 (comprising C16 : 1
ω6c and/or C16 : 1
ω7c) and C16 : 0. PFR6T also had summed feature 8 (comprising C18 :  1 ω7c and/or C18 :  1 ω6c) as a major fatty acid. The polar lipid profile of all strains contained phosphatidylethanolamine, phosphoaminoglycolipid, and phosphoglycolipid. The distinct phylogenetic, physiological, and chemotaxonomic features reported in this study indicate that strains APW6T, APW11T, and PFR6T represent novel species within the genus Roseateles, for which the names Roseateles subflavus sp. nov., with the type strain APW6T (=KACC 22877T=TBRC 16606T), Roseateles aquae sp. nov., with the type strain APW11T (=KACC 22878T=TBRC 16607T), and Roseateles violae sp. nov (=KACC 23257T=TBRC 17653T) are respectively proposed.
Hand motor recovery from post-stroke chronic severe hemiplegia with brain-computer interface based neurofeedback exercise: A randomized controlled trial
Authors: Mizuno Katsuhiro , Hayashi Masaaki , Iwama Seitaro , Nishida Daisuke , Honaga Kaoru , Fuseya Hiroshi , Hirose Ryotaro , Okuyama Kohei , Ogura-Hiramoto Miho , Kawakami Michiyuki , Ushiba Junichi , Liu Meigen 
Published: June 2024

AbstractBackgroundPost-stroke hemiplegia is a common neurological condition with a significant impact on the daily lives of patients, their families, and society. Since motor imagery and execution are supposed to share common neural networks, repeated motor imagery has been used as a common exercise for motor recovery. However, recent meta-analysis has reported inconsistent results. In the present study, we investigated whether real-time feedback of cortical activities estimated from scalp electroencephalogram (EEG) could enhance the efficacy of motor imagery-based rehabilitation in post-stroke hemiplegic patients.MethodsForty post-stroke chronic hemiplegic patients received 10 days of 40-minute mental practice with motor imagery of the paralyzed hand in addition to 40-minute standard occupational therapy. Patients were randomly allocated to REAL and CTRL groups. In the REAL group, the EEG sensorimotor rhythm recorded over the ipsilesional sensorimotor area were fed back during motor imagery though combination of visual cursor movement, neuromuscular electrical stimulation, and robotic movement support. The patients in the CTRL group wore the same EEG headset as the REAL group, but no feedback was provided. The primary outcome was the upper-extremity subscales of the Fugl-Meyer assessment (FMA). Primary outcomes were tested after 28 days of intervention using analysis of covariance models. This trial is registered with UMIN Clinical Trial Registry, UMIN000026372.FindingsFMA scores showed a significant main effect of time (p = 0·027) with an ANCOVA model considering baseline but not a significant between-group difference. However a significant interaction between time and group (p = 0•037) and greater functional gain in the REAL group (p < 0•001) were found with another model considering patient heterogeneity. The improvement was accompanied with the significant changes in the modulation index of finger extensor muscles in the affected hand in the REAL group. Moreover, imagery-related cortical activation in the sensorimotor area was significantly greater in the REAL group than in the CTRL group. No moderate or serious adverse events were confirmed in both groups.InterpretationEEG-based brain-computer interface neurofeedback may enhance the efficacy of mental practice with motor imagery and augment motor recovery in poststroke patients with chronic and severe hemiplegia.FundingSponsored by AMED under Grant Number JP18hk0102032 and JSPS KAKENHI Grant Number 20H05923.
Genetic analysis ofMycobacterium abscessusreveals genomic diversity linked to global plasmid distribution
Authors: Ohse Kensuke , Yoshida Atsushi , Kamada Keisuke , Kitazawa Hironobu , Ito Yusuke , Shoji Takayo , Watanabe Kenichiro , Koganemaru Hiroshi , Kikuchi Ken , Toyoda Masashi 
Published: June 2024

SUMMARYGenetic epidemiological analysis of mobile genetic elements, such as plasmids, has rarely been carried out inMycobacterium abscessus,regardless of its usefulness in speculating the past contact between bacteria. In this study, through whole genome sequencing analysis of clinical isolates ofM. abscessussequentially collected from the same patient, we identified a single nucleotide variant that could cause antibiotic resistance, and three plasmids (pMAB625-1, pMAB625-2 and pMAB625-3) not found in the type strain. We investigated the distribution of plasmids previously identified inM. abscessus,including pMAB625 plasmids, in 462 clinical isolates worldwidein silico. pMAB625-3 was detected in the largest number of isolates. Furthermore, phylogenetic tree analysis revealed that these plasmids transferred beyond regions and subspecies and acquired unique mutations. These results indicate that transmission of plasmids increases the genomic diversity inM. abscessus,and plasmid epidemiology is useful for estimating the past contact between bacteria.
Deciphering the regulatory pathways in skeletal muscle lineage organized by the YAP1/TAZ-TEAD transcriptional network
Authors: Gessler Lea , Siudzińska Anna , Prószyński Tomasz J. , Sandri Marco , von Eyss Björn , Hashemolhosseini Said 
Published: June 2024

ABSTRACTRecently, we reported that YAP1/TAZ-TEAD1/TEAD4 signaling regulates synaptic gene expression and acetylcholine receptor clustering at neuromuscular junctions (NMJs). Here, we looked for further impairments in skeletal muscle of Yap1 and/or Wwtr1 (protein called TAZ) conditional knockout mice. Single knockout muscles have an increased number of central nuclei and Wwtr1-deficient muscles possess more type I and less type IIa fibers. Fiber cross sectional areas were larger in Wwtr1-deficient muscles. However, adult Yap1-, but not Wwtr1-, deficient muscles showed reduced transcript levels of Axin2; Ctnnb1 was lower in both mutants. Both adult single knockout muscles transcribed less Myod and Myog. It was reported that double knockout mice do not survive past birth, likely due to the absence of NMJs. On further inspection, double knockout neonates had severely reduced muscle diameters, consistent with the impaired myogenic proliferation and sarcomere disorganization. Transcriptomic analysis demonstrates severely impaired myogenic transcription of several sarcomere genes in double knockout muscles; particularly Myh genes. Comparisons with available ChIP-seq data identified myogenic targets of YAP1/TAZ-TEAD signaling. ChIP-seq fragments of representative targets, like Myh3, Myl1, Myl2, and Ttn, overlapped with evolutionarily conserved regions and possess M-CAT motifs. Our data identified a role for YAP1/TAZ-TEAD signaling in muscle development and sarcomere structure.
Cathartocytosis: Jettisoning of Unwanted Material during Cellular Reprogramming
Authors: Brown Jeffrey W. , Lin Xiaobo , Nicolazzi Gabriel Anthony , Liu Xuemei , Nguyen Thanh , Radyk Megan D. , Burclaff Joseph , Mills Jason C. 
Published: June 2024

ABSTRACTInjury can cause differentiated cells to undergo massive reprogramming to become proliferative to repair tissue via a cellular program called paligenosis. Gastric digestive-enzyme-secreting chief cells use paligenosis to reprogram into progenitor-like Spasmolytic-Polypeptide Expressing Metaplasia (SPEM) cells. Stage 1 of paligenosis is the downscaling of mature cell architecture via a process involving lysosomes. Here, we noticed that sulfated glycoproteins were not only digested during paligenosis but also excreted into the gland lumen. Various genetic and pharmacological approaches showed that endoplasmic reticulum membranes and secretory granule cargo were also excreted and that the process proceeded in parallel with, but was mechanistically independent of autophagy. 3-dimensional light and electron-microscopy demonstrated that excretion occurred via unique, complex, multi-chambered invaginations of the apical plasma membrane. As this lysosome-independent cell cleansing process does not seem to have been priorly described, we termed it “cathartocytosis”. Cathartocytosis allows a cell to rapidly eject excess material without waiting for autophagic and lysosomal digestion. We speculate the ejection of sulfated glycoproteins would aid in downscaling and might also help bind and flush pathogens away from tissue.
Mechanism of an animal toxin-antidote system
Authors: Caro Lews , Wei Aguan D. , Thomas Christopher A. , Posch Galen , Uremis Ahmet , Franzi Michaela C. , Abell Sarah J. , Laszlo Andrew H. , Gundlach Jens H. , Ramirez Jan-Marino , Ailion Michael 
Published: June 2024

AbstractToxin-antidote systems are selfish genetic elements composed of a linked toxin and antidote. Thepeel-1 zeel-1toxin-antidote system inC. elegansconsists of a transmembrane toxin protein PEEL-1 which acts cell autonomously to kill cells. Here we investigate the molecular mechanism of PEEL-1 toxicity. We find that PEEL-1 requires a small membrane protein, PMPL-1, for toxicity. Together, PEEL-1 and PMPL-1 are sufficient for toxicity in a heterologous system, HEK293T cells, and cause cell swelling and increased cell permeability to monovalent cations. Using purified proteins, we show that PEEL-1 and PMPL-1 allow ion flux through lipid bilayers and generate currents which resemble ion channel gating. Our work suggests that PEEL-1 kills cells by co-opting PMPL-1 and creating a cation channel.
Metabolic remodelling in hiPSC-derived myofibres carrying the m.3243A>G mutation
Authors: Valdebenito Gabriel E. , Chacko Anitta R. , Chung Chih-Yao , Sheshadri Preethi , Chi Haoyu , O’Callaghan Benjamin , Houlden Henry , Rouse Hannah , Morales Valle , Bianchi Katiuscia , Tedesco Francesco Saverio , Pitceathly Robert D. S. , Duchen Michael R. 
Published: June 2024

SummaryMutations in mitochondrial DNA cause severe multisystem disease, frequently associated with muscle weakness. The m.3243A>G mutation is the major cause of Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke Like episodes (MELAS). Experimental models that recapitulate the disease phenotypein vitrofor disease modelling or drug screening are very limited. We have therefore generated hiPSC-derived muscle fibres with variable heteroplasmic mtDNA mutation load without significantly affecting muscle differentiation potential. The cells are excitable and show physiological characteristics of muscle fibres and show well organised myofibrillar structure. In cells carrying the m.3243A>G, the mitochondrial membrane potential and oxygen consumption were reduced in relation to the mutant load. We have shown through proteomic, phosphoproteomic, and metabolomic analyses that the m.3243A>G mutation variably affects the cell phenotype in relation to the mutant load. This variation is reflected by an increase in the NADH/NAD+ratio, which in turns influences key nutrient-sensing pathways in the myofibres. This model enables detailed study of the impact of the mutation on cellular bioenergetics and on muscle physiology with the potential to provide a platform for drug screening.
Diet-wide analyses for risk of colorectal cancer: prospective study of 12,250 incident cases among 543,000 women in the UK
Authors: Papier Keren , Bradbury Kathryn E , Balkwill Angela , Barnes Isobel , Smith-Byrne Karl , Gunter Marc J. , Berndt Sonja I , Le Marchand Loic , Wu Anna H , Peters Ulrike , Beral Valerie , Key Timothy J , Reeves Gillian K ,   the Million Women Study Collaborators
Published: June 2024

AbstractBackgroundApart from alcohol and processed meat, uncertainty remains regarding the role of diet in the aetiology of colorectal cancer. We conducted a large diet-wide association study of colorectal cancer risk, together with a targeted genetic analysis.MethodsWe examined associations of 97 foods and nutrients with risk of colorectal cancer in 542,778 women enrolled in the Million Women Study using multivariable-adjusted Cox regression models. We also assessed the association between genetically predicted milk intake (as a proxy of dairy and/or calcium intake) and colorectal cancer risk in the ColoRectal Transdisciplinary Study, the Colon Cancer Family Registry, and the Genetics and Epidemiology of Colorectal Cancer consortium (GECCO) using a two-sample Mendelian randomisation (MR) analysis.ResultsDuring a mean (SD) 16.6 (4.8) years of follow-up, 12,251 women were diagnosed with colorectal cancer. Seventeen dietary factors were associated with risk of colorectal cancer (False Discovery Rate <0.05). Of these associations, alcohol and calcium intakes had the strongest associations with colorectal cancer risk; a positive association for alcohol (relative risk [RR] per 20 g/day=1.15, 95% confidence interval [CI] 1.09-1.20, p<0.0000001) and an inverse association for calcium (RR per 300 mg/day=0.83, 95% CI 0.77-0.89, p<0.000001). Other dairy-related factors including dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium were also inversely associated with colorectal cancer risk, though further analysis showed that calcium intake was likely to account for these associations. Of the remaining dietary factors that were associated with colorectal cancer risk, only red and processed meat intake was associated with increased risk. Breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C were inversely associated with risk, though these associations may have been influenced by residual confounding by lifestyle and other dietary factors. In MR analyses, genetically predicted milk consumption was inversely associated with risk of colorectal cancer (RR per 200 g/day=0.60, 95% CI 0.46-0.74), colon cancer (RR per 200 g/day=0.60, 95% CI 0.43-0.77), and rectal cancer (RR per 200 g/day=0.49, 95% CI 0.31-0.67).DiscussionThis comprehensive diet-wide study provides robust evidence for the protective role of dairy milk and dairy products in colorectal cancer incidence, which is likely to be driven largely if not wholly by calcium. More research is needed to understand the potential health impacts of increasing calcium intake in some populations.
The murine lung microbiome is dysbalanced by the human pathogenic fungusAspergillus fumigatusresulting in enrichment of anaerobic bacteria
Authors: Nikitashina Liubov , Chen Xiuqiang , Radosa Lukas , Li Kexin , Straßburger Maria , Seelbinder Bastian , Böhnke Wibke , Vielreicher Sarah , Nietzsche Sandor , Heinekamp Thorsten , Jacobsen Ilse D. , Panagiotou Gianni , Brakhage Axel A. 
Published: June 2024

SummaryHere, we report significant changes in the composition of the lung microbiome and metabolome of mice under immune suppression, infection of immunosuppressed mice with virulent and avirulent strains of the clinically important human-pathogenic fungusAspergillus fumigatus, and treatment with the clinically used antifungal drug voriconazole. Our data also indicate the important role of the gut microbiome for the lung homeostasis mediated by the plasma metabolome. In the lung microbiome, infection byA. fumigatusled to a significant increase of anaerobic bacteria, most prominently ofLigilactobacillus murinus,which was confirmed by the isolation of live bacteria from the murine lower respiratory tract.In vitro,L. murinusis tolerated and even internalized by alveolar epithelial cells. Co-cultivation ofL. murinusandA. fumigatusled to a reduction in oxygen concentration accompanied by an increase ofL. murinuscells suggesting thatA. fumigatusestablishes a microaerophilic niche, thereby promoting growth of anaerobic bacteria.
Development of SYK NanoBRET Cellular Target Engagement Assays for Gain–of–Function Variants
Authors: Capener Jacob L. , Vasta James D. , Katis Vittorio L. , Michaud Ani , Beck Michael T. , Daglish Sabrina C. D. , Cohen-Kedar Sarit , Barda Efrat Shaham , Howell Stefanie , Dotan Iris , Robers Matthew B. , Axtman Alison D. , Bashore Frances M. 
Published: June 2024

AbstractSpleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that is activated by phosphorylation events downstream of FcR, B-cell and T-cell receptors, integrins, and C-type lectin receptors. When the tandem Src homology 2 (SH2) domains of SYK bind to phosphorylated immunoreceptor tyrosine-based activation motifs (pITAMs) contained within these immunoreceptors, or when SYK is phosphorylated in interdomain regions A and B, SYK is activated. SYK gain-of-function (GoF) variants were previously identified in six patients that had higher levels of phosphorylated SYK and phosphorylated downstream proteins JNK and ERK. Furthermore, the increased SYK activation resulted in the clinical manifestation of immune dysregulation, organ inflammation, and a predisposition for lymphoma. The knowledge that the SYK GoF variants have enhanced activity was leveraged to develop a SYK NanoBRET cellular target engagement assay in intact live cells with constructs for the SYK GoF variants. Herein, we developed a potent SYK-targeted NanoBRET tracer using a SYK donated chemical probe, MRL-SYKi, that enabled a NanoBRET cellular target engagement assay for SYK GoF variants, SYK(S550Y), SYK(S550F), and SYK(P342T). We determined that ATP-competitive SYK inhibitors bind potently to these SYK variants in intact live cells. Additionally, we demonstrated that MRL-SYKi can effectively reduce the catalytic activity of SYK variants, and the phosphorylation levels of SYK(S550Y) in an epithelial cell line (SW480) stably expressing SYK(S550Y).