bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐Term Safety and Efficacy of Transcatheter Microwave and Radiofrequency Denervation in a Chronic Ovine Model
Authors: Balaji Poornima , Barry Michael A. , Tran Vu Toan , Marschner Simone , Lu Juntang , Nguyen Duc Minh , Mina Ashraf , Bandodkar Sushil , Alvarez Shirley , James Virginia , Ronquillo John , Varikatt Winny , Kovoor Pramesh , McEwan Alistair , Thiagalingam Aravinda , Thomas Stuart P. , Qian Pierre C. 
Published: April 2024

Background
Transcatheter renal denervation (RDN) has had inconsistent efficacy and concerns for durability of denervation. We aimed to investigate long‐term safety and efficacy of transcatheter microwave RDN in vivo in normotensive sheep in comparison to conventional radiofrequency ablation.

Methods and Results

Sheep underwent bilateral RDN, receiving 1 to 2 microwave ablations (maximum power of 80–120 W for 240 s–480 s) and 12 to 16 radiofrequency ablations (180 s–240 s) in the main renal artery in a paired fashion, alternating the side of treatment, euthanized at 2 weeks (acute N=15) or 5.5 months (chronic N=15), and compared with undenervated controls (N=4). Microwave RDN produced substantial circumferential perivascular injury compared with radiofrequency at both 2 weeks [area 239.8 (interquartile range [IQR] 152.0–343.4) mm
2
versus 50.1 (IQR, 32.0–74.6) mm
2
,
P
<0.001; depth 16.4 (IQR, 13.9–18.9) mm versus 7.5 (IQR, 6.0–8.9) mm
P
<0.001] and 5.5 months [area 20.0 (IQR, 3.4–31.8) mm
2
versus 5.0 (IQR, 1.4–7.3) mm
2
,
P
=0.025; depth 5.9 (IQR, 1.9–8.8) mm versus 3.1 (IQR, 1.2–4.1) mm,
P
=0.005] using mixed models. Renal denervation resulted in significant long‐term reductions in viability of renal sympathetic nerves [58.9% reduction with microwave (
P
=0.01) and 45% reduction with radiofrequency (
P
=0.017)] and median cortical norepinephrine levels [71% reduction with microwave (
P
<0.001) and 72.9% reduction with radiofrequency (
P
<0.001)] at 5.5 months compared with undenervated controls.

Conclusions
Transcatheter microwave RDN produces deep circumferential perivascular ablations without significant arterial injury to provide effective and durable RDN at 5.5 months compared with radiofrequency RDN.
Finding Pattern in the Noise: Persistent Implicit Statistical Knowledge Impacts the Processing of Unpredictable Stimuli
Authors: Kóbor Andrea , Janacsek Karolina , Hermann Petra , Zavecz Zsófia , Varga Vera , Csépe Valéria , Vidnyánszky Zoltán , Kovács Gyula , Nemeth Dezso 
Published: April 2024

Abstract
Humans can extract statistical regularities of the environment to predict upcoming events. Previous research recognized that implicitly acquired statistical knowledge remained persistent and continued to influence behavior even when the regularities were no longer present in the environment. Here, in an fMRI experiment, we investigated how the persistence of statistical knowledge is represented in the brain. Participants (n = 32) completed a visual, four-choice, RT task consisting of statistical regularities. Two types of blocks constantly alternated with one another throughout the task: predictable statistical regularities in one block type and unpredictable ones in the other. Participants were unaware of the statistical regularities and their changing distribution across the blocks. Yet, they acquired the statistical regularities and showed significant statistical knowledge at the behavioral level not only in the predictable blocks but also in the unpredictable ones, albeit to a smaller extent. Brain activity in a range of cortical and subcortical areas, including early visual cortex, the insula, the right inferior frontal gyrus, and the right globus pallidus/putamen contributed to the acquisition of statistical regularities. The right insula, inferior frontal gyrus, and hippocampus as well as the bilateral angular gyrus seemed to play a role in maintaining this statistical knowledge. The results altogether suggest that statistical knowledge could be exploited in a relevant, predictable context as well as transmitted to and retrieved in an irrelevant context without a predictable structure.
T-bet suppresses proliferation of malignant B cells in chronic lymphocytic leukemia
Authors: Roessner Philipp M. , Seufert Isabelle , Chapaprieta Vicente , Jayabalan Ruparoshni , Briesch Hannah , Massoni-Badosa Ramon , Boskovic Pavle , Benckendorff Julian , Roider Tobias , Arseni Lavinia , Coelho Mariana , Chakraborty Supriya , Vaca Alicia M. , Sivina Mariela , Muckenhuber Markus , Rodriguez-Rodriguez Sonia , Bonato Alice , Herbst Sophie A. , Zapatka Marc , Sun Clare , Kretzmer Helene , Naake Thomas , Bruch Peter-Martin , Czernilofsky Felix , ten Hacken Elisa , Schneider Martin , Helm Dominic , Yosifov Deyan Y. , Kauer Joseph , Danilov Alexey V. , Bewarder Moritz , Heyne Kristina , Schneider Christof , Stilgenbauer Stephan , Wiestner Adrian , Mallm Jan-Philipp , Burger Jan A. , Efremov Dimitar G. , Lichter Peter , Dietrich Sascha , Martin-Subero José I. , Rippe Karsten , Seiffert Martina 
Published: April 2024

Abstract
The T-box transcription factor T-bet is known as a master regulator of the T-cell response but its role in malignant B cells has not been sufficiently explored. Here, we conducted single-cell resolved multi-omics analyses of malignant B cells from patients with chronic lymphocytic leukemia (CLL) and studied a CLL mouse model with a genetic knockout of Tbx21. We found that T-bet acts as a tumor suppressor in malignant B cells by decreasing their proliferation rate. NF-κB activity, induced by inflammatory signals provided by the microenvironment, triggered T-bet expression, which affected promoter-proximal and distal chromatin coaccessibility and controlled a specific gene signature by mainly suppressing transcription. Gene set enrichment analysis identified a positive regulation of interferon signaling and negative control of proliferation by T-bet. In line, we showed that T-bet represses cell cycling and is associated with longer overall survival of patients with CLL. Our study uncovered a novel tumor suppressive role of T-bet in malignant B cells via its regulation of inflammatory processes and cell cycling, which has implications for the stratification and therapy of patients with CLL. Linking T-bet activity to inflammation explains the good prognostic role of genetic alterations in the inflammatory signaling pathways in CLL.
HA-1–targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell transplantation
Authors: Krakow Elizabeth F. , Brault Michelle , Summers Corinne , Cunningham Tanya M. , Biernacki Melinda A. , Black R. Graeme , Woodward Kyle B. , Vartanian Nicole , Kanaan Sami B. , Yeh Albert C. , Dossa Robson G. , Bar Merav , Cassaday Ryan D. , Dahlberg Ann , Till Brian G. , Denker Andrew E. , Yeung Cecilia C. S. , Gooley Ted A. , Maloney David G. , Riddell Stanley R. , Greenberg Philip D. , Chapuis Aude G. , Newell Evan W. , Furlan Scott N. , Bleakley Marie 
Published: April 2024

Abstract
Relapse is the leading cause of death after allogeneic hematopoietic stem cell transplantation (HCT) for leukemia. T cells engineered by gene transfer to express T cell receptors (TCR; TCR-T) specific for hematopoietic-restricted minor histocompatibility (H) antigens may provide a potent selective antileukemic effect post-HCT. We conducted a phase 1 clinical trial using a novel TCR-T product targeting the minor H antigen, HA-1, to treat or consolidate treatment of persistent or recurrent leukemia and myeloid neoplasms. The primary objective was to evaluate the feasibility and safety of administration of HA-1 TCR-T after HCT. CD8+ and CD4+ T cells expressing the HA-1 TCR and a CD8 coreceptor were successfully manufactured from HA-1–disparate HCT donors. One or more infusions of HA-1 TCR-T following lymphodepleting chemotherapy were administered to 9 HCT recipients who had developed disease recurrence after HCT. TCR-T cells expanded and persisted in vivo after adoptive transfer. No dose-limiting toxicities occurred. Although the study was not designed to assess efficacy, 4 patients achieved or maintained complete remissions following lymphodepletion and HA-1 TCR-T, with 1 patient still in remission at &gt;2 years. Single-cell RNA sequencing of relapsing/progressive leukemia after TCR-T therapy identified upregulated molecules associated with T-cell dysfunction or cancer cell survival. HA-1 TCR-T therapy appears feasible and safe and shows preliminary signals of efficacy. This clinical trial was registered at ClinicalTrials.gov as #NCT03326921.
High-dose alemtuzumab and cyclosporine vs tacrolimus, methotrexate, and sirolimus for chronic graft-versus-host disease prevention
Authors: Holtzman Noa G. , Curtis Lauren M. , Salit Rachel B. , Shaffer Brian C. , Pirsl Filip , Ostojic Alen , Steinberg Seth M. , Schulz Eduard , Wilder Jennifer S. , Hughes Thomas E. , Rose Jeremy , Memon Sarfraz , Korngold Robert , Gea-Banacloche Juan C. , Fowler Daniel H. , Hakim Frances T. , Gress Ronald E. , Bishop Michael R. , Pavletic Steven Z. 
Published: April 2024

Abstract
Chronic graft-versus-host disease (cGVHD) remains a significant problem for patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although in vivo lymphodepletion for cGVHD prophylaxis has been explored in the myeloablative setting, its effects after reduced-intensity conditioning (RIC) are not well described. Patients (N = 83) with hematologic malignancies underwent targeted lymphodepletion chemotherapy followed by a RIC allo-HSCT using peripheral blood stem cells from unrelated donors. Patients were randomized to 2 GVHD prophylaxis arms: alemtuzumab and cyclosporine (AC; n = 44) or tacrolimus, methotrexate, and sirolimus (TMS; n = 39), with the primary end point of cumulative incidence of severe cGVHD. The incidence of severe cGVHD was lower with AC vs TMS prophylaxis at 1- and 5-years (0% vs 10.3% and 4.5% vs 28.5%; overall, P = .0002), as well as any grade (P = .003) and moderate-severe (P &lt; .0001) cGVHD. AC was associated with higher rates of grade 3 to 4 infections (P = .02) and relapse (52% vs 21%; P = .003) with no difference in 5-year GVHD-free-, relapse-free-, or overall survival. AC severely depleted naïve T-cell reconstitution, resulting in reduced T-cell receptor repertoire diversity, smaller populations of CD4Treg and CD8Tscm, but a higher ratio of Treg to naïve T-cells at 6 months. In summary, an alemtuzumab-based regimen successfully reduced the rate and severity of cGVHD after RIC allo-HSCT and resulted in a distinct immunomodulatory profile, which may have reduced cGVHD incidence and severity. However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. This trial was registered at www.ClinicalTrials.gov as #NCT00520130.
Lack of detectable sex differences in the mitochondrial function of Caenorhabditis elegans
Authors: King Dillon E. , Sparling A. Clare , Joyce Abigail S. , Ryde Ian T. , DeSouza Beverly , Ferguson P. Lee , Murphy Susan K. , Meyer Joel N. 
Published: April 2024

Abstract
Background
Sex differences in mitochondrial function have been reported in multiple tissue and cell types. Additionally, sex-variable responses to stressors including environmental pollutants and drugs that cause mitochondrial toxicity have been observed. The mechanisms that establish these differences are thought to include hormonal modulation, epigenetic regulation, double dosing of X-linked genes, and the maternal inheritance of mtDNA. Understanding the drivers of sex differences in mitochondrial function and being able to model them in vitro is important for identifying toxic compounds with sex-variable effects. Additionally, understanding how sex differences in mitochondrial function compare across species may permit insight into the drivers of these differences, which is important for basic biology research. This study explored whether Caenorhabditis elegans, a model organism commonly used to study stress biology and toxicology, exhibits sex differences in mitochondrial function and toxicant susceptibility. To assess sex differences in mitochondrial function, we utilized four male enriched populations (N2 wild-type male enriched, fog-2(q71), him-5(e1490), and him-8(e1498)). We performed whole worm respirometry and determined whole worm ATP levels and mtDNA copy number. To probe whether sex differences manifest only after stress and inform the growing use of C. elegans as a mitochondrial health and toxicologic model, we also assessed susceptibility to a classic mitochondrial toxicant, rotenone.

Results
We detected few to no large differences in mitochondrial function between C. elegans sexes. Though we saw no sex differences in vulnerability to rotenone, we did observe sex differences in the uptake of this lipophilic compound, which may be of interest to those utilizing C. elegans as a model organism for toxicologic studies. Additionally, we observed altered non-mitochondrial respiration in two him strains, which may be of interest to other researchers utilizing these strains.

Conclusions
Basal mitochondrial parameters in male and hermaphrodite C. elegans are similar, at least at the whole-organism level, as is toxicity associated with a mitochondrial Complex I inhibitor, rotenone. Our data highlights the limitation of using C. elegans as a model to study sex-variable mitochondrial function and toxicological responses.
Machine learning assists prediction of genes responsible for plant specialized metabolite biosynthesis by integrating multi-omics data
Authors: Bai Wenhui , Li Cheng , Li Wei , Wang Hai , Han Xiaohong , Wang Peipei , Wang Li 
Published: April 2024

Abstract
Background
Plant specialized (or secondary) metabolites (PSM), also known as phytochemicals, natural products, or plant constituents, play essential roles in interactions between plants and environment. Although many research efforts have focused on discovering novel metabolites and their biosynthetic genes, the resolution of metabolic pathways and identified biosynthetic genes was limited by rudimentary analysis approaches and enormous number of candidate genes.

Results
Here we integrated state-of-the-art automated machine learning (ML) frame AutoGluon-Tabular and multi-omics data from Arabidopsis to predict genes encoding enzymes involved in biosynthesis of plant specialized metabolite (PSM), focusing on the three main PSM categories: terpenoids, alkaloids, and phenolics. We found that the related features of genomics and proteomics were the top two crucial categories of features contributing to the model performance. Using only these key features, we built a new model in Arabidopsis, which performed better than models built with more features including those related with transcriptomics and epigenomics. Finally, the built models were validated in maize and tomato, and models tested for maize and trained with data from two other species exhibited either equivalent or superior performance to intraspecies predictions.

Conclusions
Our external validation results in grape and poppy on the one hand implied the applicability of our model to the other species, and on the other hand showed enormous potential to improve the prediction of enzymes synthesizing PSM with the inclusion of valid data from a wider range of species.
Crosstalk of disulfidptosis-related subtypes identifying a prognostic signature to improve prognosis and immunotherapy responses of clear cell renal cell carcinoma patients
Authors: Ren Lei , Liu Jinwen , Lin Qingyuan , He Tianyi , Huang Guankai , Wang Weifeng , Zhan Xunhao , He Yu , Huang Bin , Mao Xiaopeng 
Published: April 2024

Abstract
Background
Disulfidptosis is a novel form of programmed cell death induced by high SLC7A11 expression under glucose starvation conditions, unlike other known forms of cell death. However, the roles of disulfidptosis in cancers have yet to be comprehensively well-studied, particularly in ccRCC.

Methods
The expression profiles and somatic mutation of DGs from the TCGA database were investigated. Two DGs clusters were identified by unsupervised consensus clustering analysis, and a disulfidptosis-related prognostic signature (DR score) was constructed. Furthermore, the predictive capacity of the DR score in prognosis was validated by several clinical cohorts. We also developed a nomogram based on the DR score and clinical features. Then, we investigated the differences in the clinicopathological information, TMB, tumor immune landscapes, and biological characteristics between the high- and low-risk groups. We evaluated whether the DR score is a robust tool for predicting immunotherapy response by the TIDE algorithm, immune checkpoint genes, submap analysis, and CheckMate immunotherapy cohort.

Results
We identified two DGs clusters with significant differences in prognosis, tumor immune landscapes, and clinical features. The DR score has been demonstrated as an independent risk factor by several clinical cohorts. The high-risk group patients had a more complicated tumor immune microenvironment and suffered from more tumor immune evasion in immunotherapy. Moreover, patients in the low-risk group had better prognosis and response to immunotherapy, particularly in anti-PD1 and anti-CTLA-4 inhibitors, which were verified in the CheckMate immunotherapy cohort.

Conclusion
The DR score can accurately predict the prognosis and immunotherapy response and assist clinicians in providing a personalized treatment regime for ccRCC patients.
Selection signatures and landscape genomics analysis to reveal climate adaptation of goat breeds
Authors: Peng Weifeng , Zhang Yiyuan , Gao Lei , Shi Wanlu , Liu Zi , Guo Xinyu , Zhang Yunxia , Li Bing , Li Guoyin , Cao Jingya , Yang Mingsheng 
Published: April 2024

AbstractGoats have achieved global prominence as essential livestock since their initial domestication, primarily owing to their remarkable adaptability to diverse environmental and production systems. Differential selection pressures influenced by climate have led to variations in their physical attributes, leaving genetic imprints within the genomes of goat breeds raised in diverse agroecological settings. In light of this, our study pursued a comprehensive analysis, merging environmental data with single nucleotide polymorphism (SNP) variations, to unearth indications of selection shaped by climate-mediated forces in goats. Through the examination of 43,300 SNPs from 51 indigenous goat breeds adapting to different climatic conditions using four analytical methods: latent factor mixed models (LFMM), F-statistics (Fst), Extended haplotype homozygosity across populations (XPEHH), and spatial analysis method (SAM), A total of 74 genes were revealed to display clear signs of selection, which are believed to be influenced by climatic conditions. Among these genes, 32 were consistently identified by at least two of the applied methods, and three genes (DENND1A, PLCB1, and ITPR2) were confirmed by all four approaches. Moreover, our investigation yielded 148 Gene Ontology (GO) terms based on these 74 genes, underlining pivotal biological pathways crucial for environmental adaptation. These pathways encompass functions like vascular smooth muscle contraction, cellular response to heat, GTPase regulator activity, rhythmic processes, and responses to temperature stimuli. Of significance, GO terms about endocrine regulation and energy metabolic responses, key for local adaptation were also uncovered, including biological processes, such as cell differentiation, regulation of peptide hormone secretion, and lipid metabolism. These findings contribute to our knowledge of the genetic structure of climate-triggered adaptation across the goat genome and have practical implications for marker-assisted breeding in goats.
Epidemiological and Genomic analysis of Vibrio parahaemolyticus isolated from imported travelers at the port of Shanghai, China (2017-2019)
Authors: Liu Danlei , Zhou Lei , Zhang Zilei , Zhang Ying , Wang Zhiyi , Li Shenwei , Zhu Yongqiang , Zheng Huajun , Zhang Zilong , Tian Zhengan 
Published: April 2024

Abstract
Background
Vibrio parahaemolyticus is the predominant etiological agent of seafood-associated foodborne illnesses on a global scale. It is essential to elucidate the mechanisms by which this pathogen disseminates. Given the existing research predominantly concentrates on localized outbreaks, there is a pressing necessity for a comprehensive investigation to capture strains of V. parahaemolyticus cross borders.

Results
This study examined the frequency and genetic attributes of imported V. parahaemolyticus strains among travelers entering Shanghai Port, China, between 2017 and 2019.Through the collection of 21 strains from diverse countries and regions, Southeast Asia was pinpointed as a significant source for the emergence of V. parahaemolyticus. Phylogenetic analysis revealed clear delineation between strains originating from human and environmental sources, emphasizing that underlying genome data of foodborne pathogens is essential for environmental monitoring, food safety and early diagnosis of diseases. Furthermore, our study identified the presence of virulence genes (tdh and tlh) and approximately 120 antibiotic resistance-related genes in the majority of isolates, highlighting their crucial involvement in the pathogenesis of V. parahaemolyticus.

Conclusions
This research enhanced our comprehension of the worldwide transmission of V. parahaemolyticus and its antimicrobial resistance patterns. The findings have important implications for public health interventions and antimicrobial stewardship strategies, underscoring the necessity for epidemiological surveillance of pathogen at international travel hubs.
Factors affecting hospitalization and mortality in a retrospective study of elderly patients with heart failure
Authors: Björklund Johan , Pettersson Louise , Agvall Björn 
Published: April 2024

Abstract
Background
Heart failure (HF) has a high prevalence in an elderly population and leads to a substantial hospitalization and mortality. The objective of this study was to investigate factors that affect hospitalization and mortality in an elderly population.

Methods
A retrospective observational study was conducted of HF patients aged 76–95 years residing in Region Halland, Sweden. Between 2013 and 2019, a total of 3134 patients received a novel diagnosis of HF and were subsequently monitored for one year using data from a healthcare database. The patients were categorized into HF-phenotypes according to ejection fraction (EF) and those with HF diagnose solely based on clinical criteria with no defined EF. Cox regression analysis for hospital admissions and mortality was evaluated adjusted for pharmacotherapies, healthcare utilization and clinical characteristics.

Results
Echocardiogram was performed in 56% of the patients and 51% were treated with recommended HF pharmacotherapy with betablockers combined with renin-angiotensin-aldosterone-system inhibition. The average number of inpatient days was 10.7 while the average number of visits to primary care physician was 5.4 and 8.7 to primary care nurse respectively. A Cox regression analysis for hospital admissions and mortality revealed that an eGFR < 30 ml/min was associated with a hazard ratio (HR) of 1.88 (confidence interval [CI] 1.56–2.28), elevated NT-proBNP with an HR of 2.09 (CI 1.59–2.76), diabetes with an HR of 1.31 (CI 1.13–1.52), and chronic obstructive pulmonary disease with an HR of 1.51 (CI 1.29–1.77). Having a primary care physician visit was associated to an HR of 0.16 (CI 0.14–0.19), and the use of recommended heart failure pharmacotherapy was associated with an HR of 0.52 (CI 0.44–0.61).

Conclusions
In a Swedish elderly population with HF, factors such as advancing age, kidney dysfunction, elevated NT-proBNP levels, diabetes, and COPD were associated with an increased risk of both mortality and hospitalization. Conversely, patients who received recommended heart failure treatment and made regular visits to their primary care physician were associated with a decreased risk. This indicates that elderly patients with HF benefit from recommended HF treatment and highlights that follow-ups in primary care could be advantageous.