bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative single‐cell RNA‐seq and ATAC‐seq analysis of the evolutionary trajectory features of adipose‐derived stem cells induced into astrocytes
Authors: Long Qingxi , Yuan Yi , Ou Ya , Li Wen , Yan Qi , Zhang Pingshu , Yuan Xiaodong 
Published: December 2024

AbstractThis study employs single‐cell RNA sequencing (scRNA‐seq) and assay for transposase‐accessible chromatin with high‐throughput sequencing technologies (scATAC‐seq) to perform joint sequencing on cells at various time points during the induction of adipose‐derived stem cells (ADSCs) into astrocytes. We applied bioinformatics approaches to investigate the differentiation trajectories of ADSCs during their induced differentiation into astrocytes. Pseudotemporal analysis was used to infer differentiation trajectories. Additionally, we assessed chromatin accessibility patterns during the differentiation process. Key transcription factors driving the differentiation of ADSCs into astrocytes were identified using motif and footprint methods. Our analysis revealed significant shifts in gene expression during the induction process, with astrocyte‐related genes upregulated and stem cell‐related genes downregulated. ADSCs first differentiated into neural stem cell‐like cells with high plasticity, which further matured into astrocytes via two distinct pathways. Marked changes in chromatin accessibility were observed during ADSC‐induced differentiation, affecting transcription regulation and cell function. Transcription factors analysis identified NFIA/B/C/X and CEBPA/B/D as key regulators in ADSCs differentiation into astrocytes. We observed a correlation between chromatin accessibility and gene expression, with ADSCs exhibiting broad chromatin accessibility prior to lineage commitment, where chromatin opening precedes transcription initiation. In summary, we found that ADSCs first enter a neural stem cell‐like state before differentiating into astrocytes. ADSCs also display extensive chromatin accessibility prior to astrocyte differentiation, although transcription has not yet been initiated. These findings offer a theoretical framework for understanding the molecular mechanisms underlying this process.image
On Time‐Inconsistency in Mean‐Field Games
Authors: Bayraktar Erhan , Wang Zhenhua 
Published: December 2024

ABSTRACTWe investigate an infinite‐horizon time‐inconsistent mean‐field game (MFG) in a discrete time setting. We first present a classic equilibrium for the MFG and its associated existence result. This classic equilibrium aligns with the conventional equilibrium concept studied in MFG literature when the context is time‐consistent. Then we demonstrate that while this equilibrium produces an approximate optimal strategy when applied to the related ‐agent games, it does so solely in a precommitment sense. Therefore, it cannot function as a genuinely approximate equilibrium strategy from the perspective of a sophisticated agent within the ‐agent game. To address this limitation, we propose a new consistent equilibrium concept in both the MFG and the ‐agent game. We show that a consistent equilibrium in the MFG can indeed function as an approximate consistent equilibrium in the ‐agent game. Additionally, we analyze the convergence of consistent equilibria for ‐agent games toward a consistent MFG equilibrium as tends to infinity.
Knockdown of OsPHP1 Leads to Improved Yield Under Salinity and Drought in Rice via Regulating the Complex Set of TCS Members and Cytokinin Signalling
Authors: Yadav Chhaya , Rawat Nishtha , Singla‐Pareek Sneh L. , Pareek Ashwani 
Published: December 2024

ABSTRACTPlant two‐component system (TCS) is crucial for phytohormone signalling, stress response, and circadian rhythms, yet the precise role of most of the family members in rice remain poorly understood. In this study, we investigated the function of OsPHP1, a pseudo‐histidine phosphotransfer protein in rice, using a functional genomics approach. OsPHP1 is localised in the nucleus and cytosol, and it exhibits strong interactions with all sensory histidine kinase proteins (OsHK1‐6) and cytokinin catabolism genes. Our results demonstrate that OsPHP1 functions as a negative regulator of cytokinin signalling. Knockdown of OsPHP1 enhanced the expression of positive cytokinin signalling regulators, such as OsHKs and OsAHPs (authentic phosphotransfer proteins), while downregulating negative regulators, such as type‐A response regulators (OsRRs) and cytokinin catabolism genes (CKXs). Furthermore, OsPHP1 negatively influences abiotic stress tolerance, as evidenced by the increased sensitivity of OsPHP1‐OE (overexpression) lines to salinity and drought. In contrast, OsPHP1‐KD (knockdown) lines showed enhanced stress resilience, with better photosynthesis, increased tiller and panicle production, higher spikelet fertility, and grain filling. The study demonstrates that OsPHP1 suppresses antioxidant and stress‐responsive genes, exacerbating ion toxicity and reducing osmolyte accumulation, thereby impairing plant growth and yield under stress conditions. These findings highlight OsPHP1 as a critical modulator of plant responses to abiotic stress and suggest potential genetic targets for enhancing crop stress tolerance.
Suicide prevention inpatient group treatment—A treatment development and feasibility study
Authors: Holoshitz Yael , Mehta Haitisha , Itzhaky Liat , Cid Ariana , DeSilva Ravi , Gilbert Sarah , Kaufmann Cassie , Labouliere Christa D. , Brodsky Beth , Stanley Barbara 
Published: December 2024

AbstractBackgroundOne mainstay of psychiatric treatment for suicidal crises is inpatient psychiatric hospitalization. Despite the need to secure immediate safety and stabilization, inpatient treatment for acutely suicidal patients remains diagnosis‐specific, which may fail to directly target and adequately manage suicidal behavior as a symptom and reason for admission or treatment. The post‐discharge period is a high‐risk period for repeat suicide attempts or death by suicide, but overburdened workforce and high patient turnover make it difficult to provide suicide‐specific treatment.MethodsIn response to this need, we developed the Suicide Prevention Inpatient Group Treatment (SPIGT), a four‐module, group‐based intervention, which provides evidence‐supported concrete tools and psychoeducation to directly address suicidality. To assess feasibility and acceptability of implementation, the SPIGT was piloted on an inpatient psychiatric unit starting in 2016. Group participants were given optional, anonymous surveys after each module. Unit clinicians also completed optional, anonymous surveys to assess their attitudes towards the intervention.ResultsResults indicate that participants responded very favorably to each module, and that unit clinicians felt that the implementation of this intervention was feasible and acceptable.ConclusionThe SPIGT shows promise as a scalable suicide‐specific, brief intervention, which addresses an unmet and critical need in suicide prevention.
Flexible Tooling Enabled by the Electromagnetics With Discrete Blank Holding Force: Short-Time Pulse Control and Forming Validation
Authors: Li Lei , Hu Guozeng , Jin Rui , Du Hai , Huang Haihong 
Published: December 2024

Abstract
The increasing demand for higher precision in complex surface forming has highlighted the significance of utilizing variable blank holding force (VBHF) in segmented blank holding. However, applying electromagnetic blank holding in such segmented systems remains unexplored, presenting a critical challenge in continuous forming processes. This study proposed an innovative, flexible tooling system driven by an electrically controlled permanent magnet, enabling discrete control of blank holders. An equivalent magnetic circuit for a single magnetic pole was developed alongside a model to characterize variations in electromagnetic force. The discrete VBHF control with a short-time pulse leverages the operating point migration law of the magnet, elucidating the control mechanism of discrete electromagnetic forces. An electrical-magnetic-mechanical coupling simulation model was established using Simulink, Simplorer, and Maxwell. The simulation results reveal that the control error of electromagnetic force across different blank holding areas under varying currents ranges from 0.1% to 1.7%, with a steady-state control error under any electromagnetic force curve remaining within 5%. Electromagnetic blank holding experiments on a car-door prototype demonstrated that the control error of discrete electromagnetic forces is between −50 N and 20 N. Applying short-time pulse current in VBHF loading also ensures forming quality while reducing continuous current consumption by 14.03% and decreasing hydraulic press tonnage demand by 14%. This study provides theoretical and methodological support for designing equipment that enables low-tonnage, high-precision continuous forming of complex surfaces.
Population pharmacokinetics of piperacillin-tazobactam in the plasma and cerebrospinal fluid of critically ill patients
Authors: Kumta Nilesh , Heffernan Aaron J. , Cotta Menino Osbert , Liu Xin , Parker Suzanne , Wallis Steven , Livermore Amelia , Starr Therese , Wong Wai Tat , Joynt Gavin M. , Lipman Jeffrey , Roberts Jason A. 
Published: December 2024

ABSTRACT

Ventriculitis in neurocritical care patients leads to significant morbidity and mortality. Antibiotic dose optimization targeting pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with improved bacterial killing may improve therapeutic outcomes. We sought to develop and apply a population PK model in infected critically ill patients to determine optimal piperacillin-tazobactam (PTZ) dosing regimens to achieve target cerebrospinal fluid (CSF) exposures. Neurosurgical patients with external ventricular drains and receiving PTZ treatment were recruited and had plasma and CSF samples collected and assayed. A population PK model was developed using plasma and CSF piperacillin and tazobactam concentrations. Eight patients were recruited. Median age was 59 years, median weight was 70 kg, and five patients were female. The median creatinine clearance was 84 mL/min/1.73 m
2
(range 52–163). Substantial inter-individual PK variability was apparent, particularly in CSF. Piperacillin penetration into CSF had a median of 3.73% (range 0.73%–7.66%), and tazobactam CSF penetration was not predictable. Dosing recommendations to optimize CSF exposures for the treatment of ventriculitis were not possible due to substantial PK variability and very low drug penetration. High plasma PTZ exposures may not translate to effective exposures in CSF.
SARS-CoV-2 resistance analyses from the Phase 3 PINETREE study of remdesivir treatment in nonhospitalized participants
Authors: Rodriguez Lauren , Lee Hery W. , Li Jiani , Martin Ross , Han Dong , Xu Simin , Moshiri Jasmine , Peinovich Nadine , Camus Gregory , Perry Jason K. , Hyland Robert H. , Porter Danielle P. , Abdelghany Mazin , Götte Matthias , Hedskog Charlotte 
Published: December 2024

ABSTRACT

Remdesivir inhibits the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp; Nsp12). Here, we conducted viral resistance analyses from the Phase 3 PINETREE trial of remdesivir in nonhospitalized participants at risk of severe COVID-19. Nasopharyngeal swabs (collected at baseline [Day 1], Days 2, 3, 7, and 14) were eligible for analysis if their viral load was above the lower limit of quantification for the RT-qPCR assay (2228 copies/mL). The SARS-CoV-2 genome was sequenced for all remdesivir participants and 50% of placebo participants (baseline, Days 3, 7, and 14) and for participants who progressed to COVID-19-related hospitalization or all-cause death (all time points). Emergent substitutions in Nsp12 and other replication complex proteins were phenotyped using site-directed mutagenesis in a SARS-CoV-2 subgenomic replicon system. Overall, emergent Nsp12 substitutions were detected in 8/115 (7.0%) remdesivir participants and 7/129 (5.4%) placebo participants (1 substitution overlap between groups). Based on a structural analysis, none of the emergent Nsp12 substitutions were in direct contact with the incoming nucleoside triphosphate substrate, the RNA, or the RNA template 5′ overhang. One substitution (A376V) showed reduced susceptibility to remdesivir (12.6-fold change in remdesivir half-maximal concentration [EC
50
]); it also showed reduced fitness when introduced in the SARS-CoV-2 replicon and virus
in vitro
. Other substitutions had <1.1-fold change in remdesivir EC
50
. None of the emergent substitutions in Nsp8, Nsp10, Nsp13, or Nsp14 (remdesivir, 10/115 [8.7%]; placebo, 10/129 [7.8%]) showed reduced remdesivir susceptibility. In conclusion, emergent substitutions in the SARS-CoV-2 RdRp complex with reduced remdesivir susceptibility were uncommon, indicating a high barrier to remdesivir resistance.

CLINICAL TRIALS

This study is registered with

ClinicalTrials.gov
as
NCT04501952

.
Impact of the inoculum size on the
in vivo
activity of the aztreonam-avibactam combination in a murine model of peritonitis due to
Escherichia coli
expressing CTX-M-15 and NDM-1
Authors: Amoura Ariane , Benchetrit Laura , Magréault Sophie , Chosidow Samuel , Le Menestrel Alice , Jullien Vincent , de Lastours Victoire , Chau Françoise , Dion Sara , Massias Laurent , Fantin Bruno , Lefort Agnès 
Published: December 2024

ABSTRACT

The combination of aztreonam (ATM) and avibactam (AVI) is an attractive option to treat infections caused by extended spectrum β-lactamase plus NDM-1-producing
Enterobacteriaceae
. Since ATM activity was shown to be severely impacted by an increase in the inoculum size
in vitro
, we wondered whether ATM-AVI activity could be impaired in high-inoculum infections. We analyzed the impact of the inoculum size on ATM-AVI activity
in vitro
and in a murine model of peritonitis due to susceptible
Escherichia coli
CFT073-pTOPO and its isogenic derivatives producing NDM-1 (
E. coli
CFT073-NDM1) and CTX-M-15 plus NDM-1 (
E. coli
CFT073-CTXM15-NDM1). The impact of the inoculum size on bacterial morphology was studied by microscopic examination.
In vitro
, at standard (10
5
) inoculum,
E. coli
CFT073-CTXM15-NDM1 was resistant to ATM but susceptible to the ATM-AVI combination. At high (10
7
) inoculum, MICs of ATM alone and of the ATM-AVI combination reached >512 and 64 mg/L, respectively, against all tested strains. ATM led to bacterial filamentation when active against the bacteria, i.e., in monotherapy or in combination with AVI against susceptible
E. coli
CFT073-pTOPO and only in combination with AVI against
E. coli
CFT073-CTXM15-NDM1.
In vivo
, increase in the inoculum led to a drastic decrease in the activity of ATM alone against
E. coli
CFT073-pTOPO and ATM-AVI against
E. coli
CFT073-CTXM15-NDM1. Our results suggest a high
in vivo
impact of the inoculum increase on the activity of ATM alone against ATM-susceptible
E. coli
and of ATM-AVI against CTX-M-15 plus NDM-1 producing
E. coli
. Clinicians must be aware of the risk of failures when using ATM-AVI in high-inoculum infections.
Antibiotic resistance genes profile of selected drinking water treatment plants in South Africa as impacted by different treatment stages
Authors: Kalu Chimdi Mang , Mudau Khuthadzo L. , Ntobeng Lesoka Reneiloe , Masindi Vhahangwele , Tekere Memory 
Published: December 2024

ABSTRACT

Water treatment plants treat raw water making it suitable for consumption. Treatment stages are linked to the quality status of the treatment. The classes of antibiotic resistance genes as impacted by treatment stages remain under explored. We report the classes of antibiotic resistance genes (ARGs) from shotgun metagenomes as influenced by treatment stages.
Complete genome sequence of
Salmonella enterica
bacteriophage SeKF_80, isolated from wastewater in British Columbia
Authors: Guy Thomas , Harlton Colleen , Wang Siyun , Fong Karen 
Published: December 2024

ABSTRACT

Salmonella enterica
is a Gram-negative inhabitant of the gastrointestinal tract of warm-blooded animals and commonly implicated in foodborne illness. Here, we describe the isolation of
Salmonella enterica
phage SeKF_80. The 89,965 bp genome contains 174 predicted coding sequences with 44 predicted functions. Phage SeKF_80 shares species-level similarity with
Salmonella
phages 7–11.
Initial Experience of Contact Laser Vaporization of the Prostate (CVP) for Benign Prostate Hyperplasia Patients With Hemorrhagic Risk
Authors: Araki Yushi , Kawahara Takashi , Takeshima Teppei , Makiyama Kazuhide , Uemura Hiroji 
Published: December 2024

Introduction: Since contact laser vaporization of the prostate (CVP) was approved by the Japanese insurance system in 2016, the use of a 980 nm diode laser system for CVP has become widespread for treating benign prostate hyperplasia (BPH) patients. Our institute has been implementing CVP for BPH since 2018, treating a total of 93 patients, including 28 with a risk of hemorrhage. This study examines the safety and efficacy of CVP treatment for BPH patients with a hemorrhagic risk.Patient and Methods: A total of 93 BPH patients with lower urinary tract symptoms (LUTS) underwent CVP between February 2018 and September 2022. All patients were on medications for BPH and were refractory to these medications. The median (mean ± SD) age was 72 (72.9±6.27), and the prostate volume was 64 (68.9±32.5). IPSS, QOL index, and OABSS scores for patients not requiring catheterization were 22 (22.1±6.38), 5 (5.24±0.74), and 6 (7±3.29), respectively. The CVP treatment was performed using a 980 nm diode laser. Of the 93 patients, 28 (30.1%) had a hemorrhage risk. This group included 13 (14.0%) who were continuously receiving anticoagulant and/or antiplatelet agents, 13 (14.0%) who temporarily stopped these medications, and 2 (2.1%) who had a hemorrhage risk due to low platelet counts (< 5.0 × 104/μL).Results: Postoperatively, 15 (16.1%) patients, including 11 who were catheterized preoperatively, needed temporary catheterization after CVP treatment. Of these, 14 had their catheters successfully removed. The IPSS score significantly decreased from 22 (22.1±6.38) to 8 (9.02±6.07) (p < 0.0001). In patients with hemorrhagic risk on anticoagulant and/or antiplatelet agents, the change in hemoglobin level before and after surgery was 0.6 g/dL, a difference that was not significant. Two of the 15 patients with hemorrhagic risk experienced hemorrhage 23 and 26 days postoperatively and underwent transurethral coagulation. Other perioperative complications classified as Clavien–Dindo Grade 2 or higher occurred in 4 (4.3%) patients.Conclusion: CVP treatment appears to be acceptable for BPH patients with hemorrhagic risk. In this study, late‐onset hemorrhage occurred approximately 1 month postoperatively. Close postoperative follow‐up is required.
Angiotensin (1–7) Improves Pancreatic Islet Function via Upregulating PDX‐1 and GCK: A Dose‐Dependent Study in Mice
Authors: Lin Ziwei , Lin Jiaqi , Huang Anqi , Zhang Zixu , Wu Xinyi , Yin Guoshu , Wei Chiju , Xu Wencan 
Published: December 2024

Purpose: This study aimed to verify the effect of angiotensin (1–7) on improving islet function and further explore the signaling pathway that may be involved in this improvement. It also aimed to explore the effects of angiotensin (1–7) on blood glucose levels, islet function, and morphological changes in db/db mice and its potential signal pathway.Methods: Forty‐five db/db mice were divided randomly into a model control group and different doses of angiotensin (1–7) intervention groups (0, 150, 300, and 600 μg/kg/d), while seven db/m mice were assigned as the normal control group. The angiotensin (1–7) intervention groups received daily intraperitoneal administration for 8 weeks, whereas the normal control group was injected intraperitoneally with an equal volume of normal saline every day for 8 weeks. Changes in weight and food intake of mice were detected. Effect of angiotensin (1–7) on lipid metabolism, islet function, the morphology of pancreatic islets, and β‐cell mass on mice were evaluated. The expression of PDX‐1 and GCK in pancreatic tissue was verified.Results: The group receiving angiotensin (1–7) at a dosage of 600 μg/kg/d showed a significant decrease in body weight, triglyceride levels, and fasting blood glucose, along with an improvement in glucose tolerance. In the 300 μg/kg/d group, angiotensin (1–7) tended to increase the total volume of islets. Moreover, the intervention groups exhibited a significant increase in the ratio of β cells, small islets (30–80 μm in diameter), as well as the expression levels of PDX‐1 and GCK in pancreatic tissue.Conclusion: Angiotensin (1–7) could improve glucose and lipid metabolism and islet function by promoting the expression of PDX‐1 and GCK genes in the pancreas of db/db mice.
Patient Safety Culture and Teamwork in Hospital Wards: Registered Nurses’ and Nursing Assistants’ Perceptions and Attitudes
Authors: Hall-Lord Marie Louise , Bååth Carina , Nordin Anna 
Published: December 2024

Background: Strong patient safety culture and effective teamwork are necessary for patient safety. Registered nurses (RNs) and nursing assistants (NAs) work closely with patients, and effective teamwork and communication skills are essential.Aim: To describe and compare the perceptions of patient safety culture, teamwork, and attitudes toward teamwork among RNs and NAs in hospital wards (medical and intensive care), and to explore the potential associations between teamwork and patient safety culture.Methods: A cross‐sectional study was conducted in two hospitals in a single region of Sweden. In one hospital, RNs (n = 103) and NAs (n = 59) in medical care, and RNs (n = 41) and NAs (n = 28) in intensive care were invited to participate. In the other hospital, RNs (n = 67) and NAs (n = 66) involved in medical care were invited. The survey included the Swedish version of Hospital Survey on Patient Safety Culture (S‐HSOPS), the TeamSTEPPS Teamwork Perceptions Questionnaire (T‐TPQ), and the TeamSTEPPS Teamwork Attitudes Questionnaire (T‐TAQ).Results: In total, 155 nurses responded to the survey (response rate = 43%). Overall and in medical care, NAs had a significantly higher score than RNs in “handoffs and transitions” and in intensive care in “information and support to patients and family who have suffered an adverse event” (S‐HSOPS). RNs and NAs in intensive care reported higher scores in “communication” (T‐TPQ) than RNs and NAs in medical care. Overall and in medical care, RNs had more positive attitudes than NAs in total T‐TAQ, “mutual support,” and “communication.” T‐TPQ were associated with “overall perceptions of patient safety” and T‐TAQ were associated with “frequency of error reported.”Conclusion: This study shows differences between RNs and NAs working in medical and intensive care in their perceptions of patient safety culture, teamwork, and attitudes toward teamwork. Teamwork perceptions are important for overall patient safety.