bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrophysiology and 3D‐imaging reveal properties of human intracardiac neurons and increased excitability with atrial fibrillation
Authors: Ashton J. L. , Prince B. , Sands G. , Argent L. , Anderson M. , Smith J. E. G. , Tedoldi A. , Ahmad A. , Baddeley D. , Pereira A. G. , Lever N. , Ramanathan T. , Smaill B. H. , Montgomery Johanna M. 
Published: April 2024

AbstractAltered autonomic input to the heart plays a major role in atrial fibrillation (AF). Autonomic neurons termed ganglionated plexi (GP) are clustered on the heart surface to provide the last point of neural control of cardiac function. To date the properties of GP neurons in humans are unknown. Here we have addressed this knowledge gap in human GP neuron structure and physiology in patients with and without AF. Human right atrial GP neurons embedded in epicardial adipose tissue were excised during open heart surgery performed on both non‐AF and AF patients and then characterised physiologically by whole cell patch clamp techniques. Structural analysis was also performed after fixation at both the single cell and at the entire GP levels via three‐dimensional confocal imaging. Human GP neurons were found to exhibit unique properties and structural complexity with branched neurite outgrowth. Significant differences in excitability were revealed between AF and non‐AF GP neurons as measured by lower current to induce action potential firing, a reduced occurrence of low action potential firing rates, decreased accommodation and increased synaptic density. Visualisation of entire GPs showed almost all neurons are cholinergic with a small proportion of noradrenergic and dual phenotype neurons. Phenotypic distribution differences occurred with AF including decreased cholinergic and dual phenotype neurons, and increased noradrenergic neurons. These data show both functional and structural differences occur between GP neurons from patients with and without AF, highlighting that cellular plasticity occurs in neural input to the heart that could alter autonomic influence on atrial function.
imageKey points
The autonomic nervous system plays a critical role in regulating heart rhythm and the initiation of AF; however, the structural and functional properties of human autonomic neurons in the autonomic ganglionated plexi (GP) remain unknown.
Here we perform the first whole cell patch clamp electrophysiological and large tissue confocal imaging analysis of these neurons from patients with and without AF.
Our data show human GP neurons are functionally and structurally complex. Measurements of action potential kinetics show higher excitability in GP neurons from AF patients as measured by lower current to induce action potential firing, reduced low firing action potential rates, and decreased action potential accommodation.
Confocal imaging shows increased synaptic density and noradrenergic phenotypes in patients with AF.
Both functional and structural differences occur in GP neurons from patients with AF that could alter autonomic influence on atrial rhythm.
Becoming More Authentic as an Elite Coach: The Case Study of Erkka Westerlund
Authors: Mallett Clifford J. , Bespomoshchnov Vladislav A. , Arvaja Markus , Rynne Steven , Tiikkaja Jukka 
Published: April 2024

In this empirical case study, we examine one of Finland’s most successful and respected coaches, Erkka Westerlund. Specifically, we adopted a career-focussed approach that traces his growth as an ice hockey coach through an in-depth understanding of his journey, including his early foray into coaching at 12 years of age, his eventual dismissal as a coach at 42 years of age, his hiatus from coaching, and then his return to national and international honours. The case is comprised of multiple data sources such as semistructured interviews and a raft of secondary sources such as media publications about the participant, his autobiography, and video recordings of him speaking at various conferences and events. Data were analysed through indwelling and reflexive thematic analysis. The pivotal turning point in Erkka Westerlund’s coaching journey was a 6-year sabbatical from coaching (1991–1997). This sabbatical was transformative for him as a person and coach. Specifically, this transformation clarified and aligned his coaching and personal identities, who he was as a person (core values), and the subsequent transformation of his coaching practices that led to national and international success.
Targeted deletion of Pf prophages from diverse
Pseudomonas aeruginosa
isolates has differential impacts on quorum sensing and virulence traits
Authors: Schmidt Amelia K. , Schwartzkopf Caleb M. , Pourtois Julie D. , Burgener Elizabeth B. , Faith Dominick R. , Joyce Alex , Lamma Tyrza , Kumar Geetha , Bollyky Paul L. , Secor Patrick R. 
Published: April 2024

ABSTRACT

Pseudomonas aeruginosa
is an opportunistic bacterial pathogen that commonly causes medical hardware, wound, and respiratory infections. Temperate filamentous Pf phages that infect
P. aeruginosa
impact numerous virulence phenotypes. Most work on Pf phages has focused on Pf4 and its host
P. aeruginosa
PAO1. Expanding from Pf4 and PAO1, this study explores diverse Pf phages infecting
P. aeruginosa
clinical isolates. We describe a simple technique targeting the Pf lysogeny maintenance gene,
pflM
(
PA0718
), that enables the effective elimination of Pf prophages from diverse
P. aeruginosa
hosts. The
pflM
gene shows diversity among different Pf phage isolates; however, all examined
pflM
alleles encode the DUF5447 domain. We demonstrate that
pflM
deletion results in prophage excision but not replication, leading to total prophage loss, indicating a role for lysis/lysogeny decisions for the DUF5447 domain. This study also assesses the effects different Pf phages have on host quorum sensing, biofilm formation, pigment production, and virulence against the bacterivorous nematode
Caenorhabditis elegans
. We find that Pf phages have strain-specific impacts on quorum sensing and biofilm formation, but nearly all suppress pigment production and increase
C. elegans
avoidance behavior. Collectively, this research not only introduces a valuable tool for Pf prophage elimination from diverse
P. aeruginosa
isolates but also advances our understanding of the complex relationship between
P. aeruginosa
and filamentous Pf phages.

IMPORTANCE

Pseudomonas aeruginosa
is an opportunistic bacterial pathogen that is frequently infected by filamentous Pf phages (viruses) that integrate into its chromosome, affecting behavior. Although prior work has focused on Pf4 and PAO1, this study investigates diverse Pf in clinical isolates. A simple method targeting the deletion of the Pf lysogeny maintenance gene
pflM
(
PA0718
) effectively eliminates Pf prophages from clinical isolates. The research evaluates the impact Pf prophages have on bacterial quorum sensing, biofilm formation, and virulence phenotypes. This work introduces a valuable tool to eliminate Pf prophages from clinical isolates and advances our understanding of
P. aeruginosa
and filamentous Pf phage interactions.
Validation of a clinical assay for botulinum neurotoxins through mass spectrometric detection
Authors: Hoyt Kaitlin M. , Barr John R. , Hopkins André O. , Dykes Janet K. , Lúquez Carolina , Kalb Suzanne R. 
Published: April 2024

ABSTRACT

Botulism is a paralytic disease due to the inhibition of acetylcholine exocytosis at the neuromuscular junction, which can be lethal if left untreated. Botulinum neurotoxins (BoNTs) are produced by some spore-forming
Clostridium
bacteria. The current confirmatory assay to test for BoNTs in clinical specimens is the gold-standard mouse bioassay. However, an Endopep-MS assay method has been developed to detect BoNTs in clinical samples using benchtop mass spectrometric detection. This work demonstrates the validation of the Endopep-MS method for clinical specimens with the intent of method distribution in public health laboratories. The Endopep-MS assay was validated by assessing the sensitivity, robustness, selectivity, specificity, and reproducibility. The limit of detection was found to be equivalent to or more sensitive than the mouse bioassay. Specificity studies determined no cross-reactivity between the different serotypes and no false positives from an exclusivity panel of culture supernatants of enteric disease organisms and non-toxigenic strains of
Clostridium
. Inter-serotype specificity testing with 19 BoNT subtypes was 100% concordant with the expected results, accurately determining the presence of the correct serotype and the absence of incorrect serotypes. Additionally, a panel of potential interfering substances was used to test selectivity. Finally, clinical studies included clinical specimen stability and reproducibility, which was found to be 99.9% from a multicenter evaluation study. The multicenter validation study also included a clinical validation study, which yielded a 99.4% correct determination rate. Use of the Endopep-MS method will improve the capacity and response time for laboratory confirmation of botulism in public health laboratories.
Cannabinoid hyperemesis syndrome
Authors: Elnagar Ali , Kgomo Mpho , Mokone Modise , Yousif Badreldin 
Published: April 2024

SummaryCannabis use is legalised in many countries. We present a patient in their 40s who complained of recurrent abdominal pain and associated nausea and vomiting. The patient was previously seen in various hospitals, treated symptomatically, and discharged with a diagnosis of non-specific abdominal pain. The patient had a chronic history of smoking cannabis and nicotine and drinking alcohol. Abdominal examination revealed no masses, and abdominal X-ray was normal. Blood tests and gastroduodenoscopy revealed no obvious aetiology. Intravenous fluids, together with antiemetics and proton pump inhibitors, were administered. The patient also received counselling and was advised to stop cannabis use. At discharge, the patient was well and asked to come back for review in 2 weeks, and, thereafter monthly for a period of 6 months after stopping cannabis use. The patient reported no recurrent symptoms despite continued cigarette and alcohol use. A suspected cannabinoid hyperemesis syndrome (CHS) became a consideration. Awareness of cannabis-related disorders such as CHS may assist in avoiding costly hospital workups.
‘It’s not meant to be for life, but it carries on’: a qualitative investigation into the psychosocial needs of young retinoblastoma survivors
Authors: O'Donnell Nicola , Phillips Bob , Morgan Jessica Elizabeth , Howell Debra 
Published: April 2024

Objective and designRetinoblastoma (Rb) is a rare childhood eye cancer, with 45% of individuals impacted by heritable disease and the remainder impacted non-heritably. The condition can leave survivors with life-long psychological and social challenges. This qualitative study examined the psychosocial needs of teenagers and young adults living beyond Rb.SettingA qualitative, exploratory study was conducted using focus groups with teenagers and interviews with young adults. Participants were recruited via the Childhood Eye Cancer Trust and the two national Rb treatment centres in the UK. Reflexive thematic analysis was used to analyse data using exploratory and inductive methods.Participants32 young survivors of Rb (10 heritable, 21 non-heritable, 1 unknown; 23 unilateral, 9 bilateral) aged between 13 and 29 years (12 male, 20 female).ResultsData were rich and spanned the life course: three key themes were generated, containing eight subthemes. Theme 1 describes participants’ experiences of childhood and trauma, including survivor guilt, memories from treatment and impact on personality. Theme 2 focuses on the challenges of adolescence, including the psychological impact of Rb, the impact on identity, and the sense of normality and adaptation to late effects. The third theme considered adulthood and the development of acceptance, a state of being widely considered unachievable during childhood, as well as the ‘work’ needed to feel supported, including seeking out information, peer support and therapeutic strategies.ConclusionsThis study provides in-depth insight into the experiences of life beyond Rb. Findings highlight the need for specific psychosocial interventions informed by codesign.
Risk of cardiovascular diseases among young adults: a cross-sectional study in Malaysia
Authors: Azzani Meram , Muagan Gogilawani A P , Atroosh Wahib M , Ng Ian Zhen 
Published: April 2024

BackgroundCardiovascular disease (CVD) is the major cause of mortality worldwide. Recent studies showed that there is increasing CVD incidence at younger ages. Therefore, this study aimed to estimate the risk of CVD and its associated factors among young adults.MethodsA cross-sectional study was conducted among university students in Selangor, Malaysia, using a self-administered questionnaire along with anthropometric measurements. The sample size was calculated using a single proportion formula. The CVD risk was calculated using the non-laboratory-based Inter-Heart Modifiable Risk Score (IHMRS). Participants aged 18 years and above, with no CVD history, were recruited using a convenience sampling method between February and May 2022. CVD risk was classified as low (scores between 0 and 9 points), moderate (scores between 10 and 15 points) and high (scores between 16 and 48 points). The factors associated with the CVD risk were identified using χ2analysis.ResultsA total of 241 participants were included in this study. The median age was 28 years and the majority were females (75.1%). The IHMRS revealed that 46.5%, 44.4% and 9% of the respondents have low, moderate and high CVD risk, respectively. The CVD risk associated factors were education, the history of heart attacks among parents, feeling sad or depressed for 2 weeks or more in a row, having several episodes/permanent stress, expose to secondhand smoke and consuming meat and poultry more than two times daily.ConclusionsThis study found that more than 50% of study participants had moderate to high risk of CVD. Family history and lifestyle factors are the most likely determinants of CVD risk among the young age group. These findings support the development and implementation of targeted prevention programmes as well as provide useful information for action planning and policymaking to curb the disease in the future.
Regional versus general anesthesia for total hip and knee arthroplasty: a nationwide retrospective cohort study
Authors: Oh Tak Kyu , Song In-Ae 
Published: April 2024

IntroductionWe aimed to determine whether regional anesthesia (RA) has any advantages over general anesthesia (GA) in total joint arthroplasty (TJA) in terms of mortality and postoperative complications.MethodsThis population-based retrospective cohort study included data of adults who underwent total knee or hip arthroplasty under RA or GA between 2016 and 2021 from the National Health Insurance Service of South Korea. RA included spinal or epidural anesthesia or a combination of both. Endpoints were 30-day mortality, 90-day mortality, and postoperative complications. Propensity score (PS) matching was used for statistical analysis.ResultsWe included 517 960 patients (RA, n=380 698; GA, n=137 262) who underwent TJA. After PS matching, 186 590 patients (93 295 in each group) were included in the final analysis. In the logistic regression analyses using the PS-matched cohort, the RA group compared with the GA group showed 31% (OR: 0.69; 95% CI, 0.60 to 0.80; p<0.001) and 22% (OR: 0.78; 95% CI, 0.72 to 0.85; p<0.001) lower 30-day and 90-day mortality rates, respectively. However, the total postoperative complication rate did not differ significantly between the two groups (p=0.105).ConclusionRA compared with GA was associated with improved 30-day and 90-day survival outcomes in patients who underwent TJA. However, the postoperative complication rate did not differ significantly. Therefore, our results should be interpreted with caution, and more well-designed future studies are needed to clarify the most appropriate type of anesthesia for TJA.
Analysis of water migration in an earthen landfill cover with recycled construction waste
Authors: Guo Haowen , Ng Charles Wang Wai , Zhang Qi , Wei Wei 
Published: April 2024

In this study, numerical analysis was conducted to investigate the effects of particle sizes on water migration in a three-layer landfill cover system using recycled concrete aggregates (RCAs). This cover system consists of a top fine recycled concrete (FRC) aggregate layer and a middle coarse recycled concrete aggregate layer overlying a bottom silty refuse soil layer. Numerical simulations were performed to back analyse a flume model test data and further evaluate the particle size effects of RCAs on the effectiveness of the cover system. With the increase in rainfall duration, surface runoff reduced, while the lateral diversion increased pronouncedly. Nonetheless, no significant percolation is observed through the cover system using RCAs during 100-year extreme rainfall with different durations. Based on the results, the d10 of FRC is recommended to be from 0.2 to 0.5 mm.
Constraining on the non-standard cosmological models combining the observations of high-redshift quasars and BAO
Authors: Liu Ziqiang , Liu Tonghua , Zhong Xinyi , Xu Yifei , Zheng Xiaogang 
Published: April 2024

AbstractIn this work, we studied four types of cosmological models with different mechanisms driving the accelerated expansion of the universe, include Braneworld models, Chaplygin Gas models, Emergent Dark Energy models, and cosmological torsion models. Considering that the dynamics of these models at low redshifts are very similar and difficult to distinguish, we used the latest and largest UV and X-ray measurements of quasars (QSOs) observations covering the range of redshift $$0.009<z<7.5$$

0.009
<
z
<
7.5

. However, the high intrinsic dispersion of this sample and the degeneracy between cosmological model parameters, we added 2D-BAO and 3D-BAO datasets to help us constrain the parameters of these cosmological models. Our results suggest that standard cold dark matter scenario may not be the best cosmological model preferred by the high-redshift observations. The Generalized Chaplygin Gas (GCG) and cosmological constant plus torsion (named Case II) models perform best by Akaike Information Criterion (AIC), but the $$\Lambda $$
Λ
CDM is the best cosmological model preferred by Bayesian Information Criterion (BIC). Our work also supports that the Phenomenologically Emergent Dark Energy and cosmological torsion models may alleviate the Hubble tension, the reported value of the Hubble constant obtained from QSO+BAO datasets combination lies between Planck 2018 observations and local measurements from the SH0ES collaboration, while other cosmological models all support that the Hubble constant tends to be closer to recent Planck 2018 results, but these model are penalized by information criterion.
Impaired Sensitivity to Thyroid Hormones Is Associated With the Change of Abdominal Fat in Euthyroid Type 2 Diabetes Patients: A Retrospective Cohort Study
Authors: Cao Bin , Li Kun , Ke Jing , Zhao Dong 
Published: April 2024

Background and Aims: This study is aimed at investigating the potential correlation of thyroid hormone sensitivity with visceral fat area (VFA), subcutaneous fat area (SFA), and body mass index (BMI) among euthyroid type 2 diabetes mellitus (T2DM) subjects.Methods: Thyroid hormone sensitivity indices were calculated by thyroid feedback quantile–based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free thyroxine (fT4)/free triiodothyronine (fT3) ratio. These indices were then categorized into quartiles for analysis. The outcomes were the change rates in VFA, SFA, and BMI among the participants.Result: The present study included 921 patients, with a median follow‐up of 2.2 years. In multivariate linear regression, when compared to the first quartile, SFA demonstrated a notable decline in the fourth quartile of TFQI, TSHI, and TT4RI (β coefficient = −5.78, −7.83, and − 6.84 cm2 per year), while it significantly increased in the fourth quartile of fT4/fT3 ratio (β coefficient = 6.13 cm2 per year). Similarly, in the fourth quartile of TFQI, TSHI, and TT4RI, VFA decreased significantly, evidenced by β coefficients of −5.14, −4.80, and −4.08 cm2 per year. Yet, among the quartiles of the fT4/fT3 ratio, no discernible trend in VFA was observed. There was no significant association between indices of thyroid hormone sensitivity and change in BMI.Conclusion: Impaired central sensitivity to thyroid hormones was significantly associated with the reduction of VFA and SFA, while impaired peripheral sensitivity was associated with an increase of SFA in euthyroid individuals with T2DM.
T-Cell Characteristics Impact Response and Resistance to T-Cell–Redirecting Bispecific Antibodies in Multiple Myeloma
Authors: Verkleij Christie P.M. , O’Neill Chloe A. , Broekmans Marloes E.C. , Frerichs Kristine A. , Bruins Wassilis S.C. , Duetz Carolien , Kruyswijk Sandy , Baglio Serena R. , Skerget Sheri , Montes de Oca Rocio , Zweegman Sonja , Verona Raluca I. , Mutis Tuna , van de Donk Niels W.C.J. 
Published: April 2024

Abstract

Purpose:
Bispecific antibodies (BsAb) directed against B-cell maturation antigen (teclistamab) or the orphan G protein-coupled receptor GPRC5D (talquetamab) induce deep and durable responses in heavily pretreated patients with multiple myeloma. However, mechanisms underlying primary and acquired resistance remain poorly understood.

Experimental Design:
The anti–multiple myeloma activity of teclistamab and talquetamab was evaluated in bone marrow (BM) samples from patients with multiple myeloma. T-cell phenotype and function were assessed in BM/peripheral blood samples obtained from patients with multiple myeloma who were treated with these BsAb.

Results:
In ex vivo killing assays with 41 BM samples from BsAb-naive patients with multiple myeloma, teclistamab- and talquetamab-mediated multiple myeloma lysis was strongly correlated (r = 0.73, P &lt; 0.0001). Both BsAb exhibited poor activity in samples with high regulatory T-cell (Treg) numbers and a low T-cell/multiple myeloma cell ratio. Furthermore, comprehensive phenotyping of BM samples derived from patients treated with teclistamab or talquetamab revealed that high frequencies of PD-1+ CD4+ T cells, CTLA4+ CD4+ T cells, and CD38+ CD4+ T cells were associated with primary resistance. Although this lack of response was linked to a modest increase in the expression of inhibitory receptors, increasing T-cell/multiple myeloma cell ratios by adding extra T cells enhanced sensitivity to BsAb. Further, treatment with BsAb resulted in an increased proportion of T cells expressing exhaustion markers (PD-1, TIGIT, and TIM-3), which was accompanied by reduced T-cell proliferative potential and cytokine secretion, as well as impaired antitumor efficacy in ex vivo experiments.

Conclusions:
Primary resistance is characterized by a low T-cell/multiple myeloma cell ratio and Treg-driven immunosuppression, whereas reduced T-cell fitness due to continuous BsAb-mediated T-cell activation may contribute to the development of acquired resistance.