bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current research insights into the role of CTLA‐4 in hepatitis B virus (HBV) infection
Authors: Gu Qi , Yin Shengxia , Tong Xin , Rui Fajuan , Zhu Yixuan , Ma Xiaoyan , Huang Rui , Wu Chao , Li Jie 
Published: May 2024

AbstractChronic hepatitis B virus (HBV) infection is a significant global public health concern, and the clearance of HBV is closely linked to the activity of HBV‐specific T cells, which is regulated by various co‐suppressor molecules. Cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) is among these co‐suppressor molecules which induces T cell exhaustion by competitively inhibiting CD28 and dampening the function of HBV‐specific T cells. CTLA‐4 also plays a role in the regulation of T helper (Th) cell differentiation and influences cytokine release. In addition, CTLA‐4 can impact glucose metabolism in hepatocellular carcinoma through its interaction with T regulatory (Treg) cells. This review aims to provide a comprehensive overview of the existing literature related to the role of CTLA‐4 in HBV patients across different subsets of T cells. Additionally, we propose a discussion on the possible mechanisms through which CTLA‐4 may contribute to HBV infection, as well as the development of HBV‐induced cirrhosis and hepatocellular carcinoma.
Exploring interspecific hybridization dynamics in artificial forests of Pinus brutia and P. halepensis: Implications for sustainable afforestation
Authors: Houminer Naomi , Osem Yagil , Riov Joseph , Sherman Amir , Rozen Ada , Sela Hanan , David‐Schwartz Rakefet 
Published: May 2024

AbstractInterspecific hybridization increases genetic diversity, which is essential for coping with changing environments. Hybrid zones, occurring naturally in overlapping habitats of closely related species, can be artificially established during afforestation. The resulting interspecific hybridization may promote sustainability in artificial forests, particularly in regions facing degradation due to climate change. Currently, there is limited evidence of hybridization during regeneration of artificial forests. Here, we studied the frequency of Pinus brutia Ten. × P. halepensis Mill. hybridization in five planted forests in Israel in three stages of forest regeneration: seeds before dispersal, emerged seedlings and recruited seedlings at the end of the dry season. We found hybrids on P. brutia, but not on P. halepensis trees due to asynchronous cone production phenology. Using 94 single‐nucleotide polymorphism (SNP) markers, we found hybrids at all stages, most of which were hybrids of advanced generations. The hybrid proportions increased from 4.7 ± 2.1 to 8.2 ± 1.4 and 21.6 ± 6.4 per cent, from seeds to emerged seedlings and to recruited seedlings stages, respectively. The increased hybrid ratio implies an advantage of hybrids over P. brutia during forest regeneration. To test this hypothesis, we measured seedling growth rate and morphological traits under controlled conditions and found that the hybrid seedlings exhibited selected traits of the two parental species, which likely contributed to the fitness and survival of the hybrids during the dry season. This study highlights the potential contribution of hybrids to sustainable‐planted forests and contributes to the understanding of genetic changes that occur during the regeneration of artificial forests.
Multiple regulatory inputs including cell envelope stress orchestrate expression of the Escherichia coli rpoN operon
Authors: Sikora Florian , Budja Lara Veronika Perko , Milojevic Olja , Ziemniewicz Amelia , Dudys Przemyslaw , Görke Boris 
Published: May 2024

AbstractThe rpoN operon, an important regulatory hub in Enterobacteriaceae, includes rpoN encoding sigma factor σ54, hpf involved in ribosome hibernation, rapZ regulating glucosamine‐6‐phosphate levels, and two genes encoding proteins of the nitrogen‐related phosphotransferase system. Little is known about regulatory mechanisms controlling the abundance of these proteins. This study employs transposon mutagenesis and chemical screens to dissect the complex expression of the rpoN operon. We find that envelope stress conditions trigger read‐through transcription into the rpoN operon from a promoter located upstream of the preceding lptA‐lptB locus. This promoter is controlled by the envelope stress sigma factor E and response regulator PhoP is required for its full response to a subset of stress signals. σE also stimulates ptsN‐rapZ‐npr expression using an element downstream of rpoN, presumably by interfering with mRNA processing by RNase E. Additionally, we identify a novel promoter in the 3′ end of rpoN that directs transcription of the distal genes in response to ethanol. Finally, we show that translation of hpf and ptsN is individually regulated by the RNA chaperone Hfq, perhaps involving small RNAs. Collectively, our work demonstrates that the rpoN operon is subject to complex regulation, integrating signals related to envelope stress and carbon source quality.
Surgical Treatment Outcomes of Anterior‐Only Correction and Reconstruction for Severe Cervical Kyphotic Deformity with Neurofibromatosis‐1: A Retrospective Study with a 5‐Year Follow‐Up
Authors: Li Qiujiang , Wang Liang , Yang Huiliang , Yang Xi , Liu Limin , Wang Lei , Song Yueming 
Published: May 2024

ObjectivesCurrently, anterior‐only (AO), posterior‐only, and combined anterior–posterior spinal fusions are common strategies for treating cervical kyphosis in patients with neurofibromatosis‐1 NF‐1. Nevertheless, the choice of surgical strategy remains a topic of controversy. The aim of our study is to evaluate the safety and effectiveness of anterior decompression and spinal reconstruction for the treatment of cervical kyphosis in patients with NF‐1.MethodsTwelve patients with NF‐1‐associated cervical kyphotic deformity were reviewed retrospectively between January 2010 and April 2020. All patients underwent AO correction and reconstruction. The X‐ray was followed up in all these patients to assess the preoperative and postoperative local kyphosis angle (LKA), the global kyphosis angle (GKA), the sagittal vertical axis, and the T1 slope. The visual analog scale score, Japanese Orthopedic Association (JOA) score, and neck disability index (NDI) score were used to evaluate the improvement inclinical symptoms. The results of the difference in improvement from preoperatively to the final follow‐up assessment were assessed using a paired t‐test or Mann–Whitney U‐test.ResultsThe LKA and GKA decreased from the preoperative average of 64.42 (range, 38–86) and 35.50 (range, 10–81) to an average of 16.83 (range, −2 to 46) and 4.25 (range, −22 to 39) postoperatively, respectively. The average correction rates of the LKA and GKA were 76.11% and 111.97%, respectively. All patients had achieved satisfactory relief of neurological symptoms (p < 0.01). JOA scores were improved from 10.42 (range, 8–16) preoperatively to 15.25 (range, 11–18) at final follow‐up (p < 0.01). NDI scores were decreased from an average of 23.25 (range, 16–34) preoperatively to an average of 7.08 (range, 3–15) at the final follow‐up (p < 0.01).ConclusionAnterior‐only correction and reconstruction is a safe and effective method for correcting cervical kyphosis in NF‐1 patients. In fixed cervical kyphosis cases, preoperative skull traction should also be considered.
Population pharmacokinetics and pharmacodynamic target attainment analysis of cefazolin using total and unbound serum concentration in patients with prostatectomy or nephrectomy
Authors: Komatsu Toshiaki , Kawai Yuka , Takayama Yoko , Akamada Yuto , Kusume Eri , Ikeda Masaomi , Tsumura Hideyasu , Ishii Daisuke , Iwamura Masatsugu , Okamoto Hirotsugu , Hanaki Hideaki , Otori Katsuya 
Published: May 2024

ABSTRACT

The aim of this study was to analyze the population pharmacokinetics of total and unbound concentrations of prophylactic cefazolin (CFZ) in patients with prostatectomy or nephrectomy. We also aimed to calculate a pharmacodynamics target unbound concentration that exceeded the minimum inhibitory concentration (MIC), to design an effective dosing regimen. Briefly, 614 total concentration and 610 unbound concentration samples from 152 individuals were evaluated, using a nonlinear mixed-effects model. The obtained pharmacodynamics index target value reflected the probability of maintaining CFZ unbound trough concentrations exceeding MIC
90
, 0.5 mg/L, and MIC
50
, and 1.0 mg/L, to account for methicillin-susceptible
Staphylococcus aureus
(MSSA) or
Escherichia coli
. Population pharmacokinetics were estimated using a two-compartment model with nonlinear protein binding. Unbound systemic clearance (CL) was significantly associated with creatinine clearance, while the maximum protein-binding constant was significantly associated with albumin levels. The probability of achieving an unbound concentration exceeding the MIC
50
for
E. coli
or MIC
90
for MSSA in a patient with normal renal function following a 1 g CFZ infusion over 15 min was above 90% at 3 h after the initial dose. Our findings indicated that population pharmacokinetic parameters are useful for determining unbound CFZ pharmacokinetics and evaluating intraoperative CFZ redosing intervals.
Cryptic environmental conjugative plasmid recruits a novel hybrid transposon resulting in a new plasmid with higher dispersion potential
Authors: Muñoz-Gutiérrez Iván , Cantu Luis , Shanahan Jack , Girguis Miray , de la Cruz Marlene , Mota-Bravo Luis 
Published: May 2024

ABSTRACT

Cryptic conjugative plasmids lack antibiotic-resistance genes (ARGs). These plasmids can capture ARGs from the vast pool of the environmental metagenome, but the mechanism to recruit ARGs remains to be elucidated. To investigate the recruitment of ARGs by a cryptic plasmid, we sequenced and conducted mating experiments with
Escherichia coli
SW4848 (collected from a lake) that has a cryptic IncX (IncX4) plasmid and an IncF (IncFII/IncFIIB) plasmid with five genes that confer resistance to aminoglycosides (
strA
and
strB
), sulfonamides (
sul2
), tetracycline [
tet
(
A
)], and trimethoprim (
dfrA5
). In a conjugation experiment, a novel hybrid Tn21/Tn1721 transposon of 22,570 bp (designated Tn7714) carrying the five ARG mobilized spontaneously from the IncF plasmid to the cryptic IncX plasmid. The IncF plasmid was found to be conjugative when it was electroporated into
E. coli
DH10B (without the IncX plasmid). Two parallel conjugations with the IncF and the new IncX (carrying the novel Tn7714 transposon) plasmids in two separate
E. coli
DH10B as donors and
E. coli
J53 as the recipient revealed that the conjugation rate of the new IncX plasmid (with the novel Tn7714 transposon and five ARGs) is more than two orders of magnitude larger than the IncF plasmid. For the first time, this study shows experimental evidence that cryptic environmental plasmids can capture and transfer transposons with ARGs to other bacteria, creating novel multidrug-resistant conjugative plasmids with higher dispersion potential.

IMPORTANCE
Cryptic conjugative plasmids are extrachromosomal DNA molecules without antibiotic-resistance genes (ARGs). Environmental bacteria carrying cryptic plasmids with a high conjugation rate threaten public health because they can capture clinically relevant ARGs and rapidly spread them to pathogenic bacteria. However, the mechanism to recruit ARG by cryptic conjugative plasmids in environmental bacteria has not been observed experimentally. Here, we document the first translocation of a transposon with multiple clinically relevant ARGs to a cryptic environmental conjugative plasmid. The new multidrug-resistant conjugative plasmid has a conjugation rate that is two orders of magnitude higher than the original plasmid that carries the ARG (i.e., the new plasmid from the environment can spread ARG more than two orders of magnitude faster). Our work illustrates the importance of studying the mobilization of ARGs in environmental bacteria. It sheds light on how cryptic conjugative plasmids recruit ARGs, a phenomenon at the root of the antibiotic crisis.
Human plasma-like medium (HPLM) induces
Cryptococcus neoformans in vivo
cell morphologies
Authors: G. Mozo Eduardo , Ross Orlando , Yuecel Raif , Dambuza Ivy M. , Mukaremera Liliane 
Published: May 2024

ABSTRACT

The fungal pathogen
Cryptococcus neoformans (C. neoformans
) forms yeast cells of different sizes and morphological characteristics during infection. These features are usually not seen in standard laboratory
in vitro
conditions. Here, we describe
in vivo
cell morphologies when
C. neoformans
is grown in human plasma-like medium at 37°C, 5% CO
2
. We observed mixed-size populations of cells less than 1 µm up to 16.8 µm in cell diameter, increased capsule size, high chitin, and DNA content in larger cells. Our findings show that serum is not required for human plasma-like medium (HPLM)-induced
C. neoformans
cellular heterogeneity. Thus, this new method offers an opportunity to investigate factors of
C. neoformans
that mediate pathogenesis or host–pathogen interactions in a physiologically relevant setting.

IMPORTANCE

We provide a description of new
in vitro
culture condition using the human plasma-like medium that supports the formation of the full range of
in vivo
cell morphologies of
C. neoformans
.
Evaluating a novel online behavioural intervention to encourage cost-conscious strategies among US adults with chronic conditions who are enrolled in a high-deductible health plan: a proof-of-concept pilot study
Authors: Peirce Alexandra , Lin Ying-Jen , Fagerlin Angela , Heisler Michele , Levy Helen , Kullgren Jeffrey 
Published: May 2024

ObjectivesPatients with chronic conditions enrolled in high-deductible health plans (HDHPs) face cost-related access barriers and high out-of-pocket spending. Our objectives were to develop a novel behavioural intervention to help HDHP enrollees with chronic conditions use cost-conscious strategies and evaluate the intervention’s preliminary effectiveness, acceptability and feasibility.DesignProspective.SettingOnline (USA).Participants36 US adults enrolled in an HDHP through their employer or an exchange with diabetes, hypertension, asthma, coronary artery disease and/or chronic obstructive pulmonary disease. 31/36 participants completed the study.InterventionWe developed a 5-week intervention consisting of a website with educational modules on discussing costs with clinicians, saving for future healthcare costs, comparing healthcare prices and quality, preparing for appointments, following up after appointments and planning for future healthcare needs; and emails encouraging participants to access each module.OutcomesWe conducted a single-arm proof-of-concept pilot study of the intervention. Baseline and postintervention surveys measured primary outcomes of health insurance literacy and confidence in using cost-conscious strategies. 10 participants completed postintervention interviews.Results31 (86%) participants completed a baseline and postintervention survey. Mean health insurance literacy scores (20–80 scale) improved from 56.5 to 67.1 (p<0.001). Mean confidence scores (0–10 scale) improved for talking to a healthcare provider about cost (6.1–7.6, p=0.0094), saving for healthcare (5.8–6.6, p=0.068), comparing prices (5.4–6.9, p=0.005) and comparing quality (6.1 to 7.6, p=0.0034). Participants found the website easy to use and helpful for learning about cost-conscious strategies on postintervention interviews.ConclusionsOur novel behavioural intervention was acceptable to HDHP enrollees with chronic conditions, feasible to deliver and associated with increased health insurance literacy and confidence in using cost-conscious strategies. This intervention should be tested in a definitive randomised controlled trial that is fully powered to evaluate its effects on cost-related access barriers, out-of-pocket spending and health outcomes in this growing patient population.
Protocol for a pragmatic randomised controlled feasibility study ofMS WorkSmart: an online intervention for Australians with MS who are employed
Authors: van der Mei Ingrid , Thomas Sarah , Shapland Sue , Laslett Laura L , Taylor Bruce V , Huglo Alisée , Honan Cynthia 
Published: May 2024

IntroductionMultiple sclerosis (MS) causes a wide variety of symptoms. Loss of income due to sickness and early retirement comprise one-third of the total cost of MS in Australia. An intervention that maximises work productivity and keeps people with MS in the workforce for longer could provide a large societal cost saving and improve quality of life. The aim is to test the feasibility of delivering and evaluating a 10-week digitally delivered intervention called ‘MS WorkSmart’. Findings will provide insights into participant profiles and address key methodological and procedural uncertainties (recruitment, retention, intervention adherence and engagement, and selection of primary outcome) in preparation for a subsequent definitive trial.Methods and analysisA parallel-arm randomised controlled feasibility study, comparing those randomised to receive the MS WorkSmart package plus usual care (n=20) to those receiving usual care only (n=20). Australians with MS, aged 18–60 years, who are employed, and self-report work instability will be recruited from the Australian MS Longitudinal Study. Online surveys, at baseline and 1-month postintervention, will include MS-related work productivity loss and risk of job loss, MS work behaviour self-efficacy, health-related quality of life, fatigue severity, MS symptom impact on work, intention to retire due to MS, MS-related work difficulties, and awareness and readiness for change at work. Qualitative feedback will be obtained via a semistructured survey following the intervention (for participants) and via interviews (coaches). Analyses will be primarily descriptive and focus on the feasibility and acceptability of the intervention and study procedures. Progression criteria will guide decisions around whether to progress to a full trial.Ethics and disseminationThe study has been approved by the University of Tasmania Human Research Ethics Committee (H0024544). Findings will be disseminated via publication in peer-reviewed journals, conference presentations and community presentations.Trial registration numberACTRN12622000826741.
Protocol for process evaluation of ARTEMIS cluster randomised controlled trial: an intervention for management of depression and suicide among adolescents living in slums in India
Authors: Mukherjee Ankita , Yatirajula Sandhya Kanaka , Kallakuri Sudha , Paslawar Srilatha , Lempp Heidi , Raman Usha , Kumar Ashok , Essue Beverley M , Sagar Rajesh , Singh Renu , Peiris David , Norton Robyn , Thornicroft Graham , Maulik Pallab Kumar 
Published: May 2024

IntroductionThere are around 250 million adolescents (10–19 years) in India. The prevalence of mental health-related morbidity among adolescents in India is approximately 7.3%. Vulnerable subpopulations among adolescents such as those living in slum communities are particularly at risk due to poor living conditions, financial difficulty and limited access to support services. Adolescents’ Resilience and Treatment nEeds for Mental Health in Indian Slums (ARTEMIS) is a cluster randomised controlled trial of an intervention that intends to improve the mental health of adolescents living in slum communities in India. The aim of this paper is to describe the process evaluation protocol for ARTEMIS trial. The process evaluation will help to explain the intervention outcomes and understand how and why the intervention worked or did not work. It will identify contextual factors, intervention barriers and facilitators and the adaptations required for optimising implementation.MethodsCase study method will be used and the data will include a mix of quantitative metrics and qualitative data. The UK Medical Research Council’s guidance on evaluating complex interventions, the Reach, Efficacy, Adoption, Implementation and Maintenance Framework and the Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Safety/Side Effects and, Equity criteria will be used to develop a conceptual framework and a priori codes for qualitative data analysis. Quantitative data will be analysed using descriptive statistics. Implementation fidelity will also be measured.DiscussionThe process evaluation will provide an understanding of outcomes and causal mechanisms that influenced any change in trial outcomes.Ethics and disseminationEthics Committee of the George Institute for Global Health India (project number 17/2020) and the Research Governance and Integrity Team, Imperial College, London (ICREC reference number: 22IC7718) have provided ethics approval. The Health Ministry’s Screening Committee has approved to the study (ID 2020-9770).Trial registration numberCTRI/2022/02/040307.
Who dies from venous thromboembolism after hospitalisation for other reasons in England?: a national retrospective cohort study
Authors: Healey Frances , Gower Janine , Roberts Lara , Arya Roopen , Beresford Matthew , Fowler Aidan , Kirkpatrick Graeme , Oldfield Ethel , Weaver Rachel 
Published: May 2024

ObjectivesVenous thromboembolism (VTE) is a major cause of morbidity and mortality globally, with hospital-associated thrombosis (HAT) accounting for at least half of VTE. We set out to understand more about deaths from HAT in England, to focus improvement efforts where they are needed most.DesignA retrospective cohort combining death certification and hospital activity data to identify people with an inpatient or day case hospitalisation where no VTE diagnosis was recorded, and who died from VTE in a hospital or within 90 days of discharge, between April 2017 and March 2020.SettingAll deaths occurring in England and all National Health Service-funded hospital care in England.ParticipantsAfter 0.1% of cases were excluded due to duplicate but conflicting records, a cohort of 13 995 deaths remained; 54% were women, and 26% were aged under 70 years.Outcome measuresAnalysis of age, gender, primary diagnosis, type of admission, specialties and (for day cases) procedure types were preplanned.ResultsOnly 5% of these deaths followed planned inpatient admissions. Day case admissions preceded 7% of VTE deaths. Emergency inpatient admissions, medical specialties and infection-related primary diagnoses predominated in people who died from VTE after hospitalisation where no VTE diagnosis was recorded. Most deaths occurred in a hospital or within 30 days of discharge.ConclusionsInternational efforts to reduce HAT historically focused on planned inpatient admissions. Further initiatives and research to prevent deaths from VTE after hospitalisation should focus on the emergency care pathway where most deaths occurred, with people undergoing day case procedures an important additional focus.