bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can compassionate leadership of senior hospital leaders help retain trainee doctors?
Authors: Wang Wen , Creese Jennifer , Karanika-Murray Maria , Harris Kevin , McCarthy Mark , Leng Christopher , King Christopher 
Published: June 2024

BackgroundHigh burnout and low retention rates among trainee doctors threaten the future viability of the UK medical workforce. This study empirically examined factors that can sustain trainee doctors.MethodA total of 323 trainee doctors from 25 National Health Service (NHS) Trusts in England and Wales completed an online survey on their training and employment experiences. A mixed method approach was employed.ResultsStructural equation modelling revealed that perceived compassionate leadership of hospital senior leaders (CLSL) (i.e., doctors in senior clinical and management positions, and senior managers) is directly and negatively associated with trainee doctors’ burnout and intention to quit. We propose the associations may be indirectly strengthened through two mediating pathways: increased psychological contract fulfilment (PCF) of training/organisational support and reduced worry about the state of the NHS; however, only the former is supported. The model can explain a substantial 37% of the variance in reported burnout and 28% of intention to quit among trainee doctors. Being a Foundation Year (FY) trainee was significantly associated with poor PCF and burnout. Rich qualitative data further elaborated on their experiences in terms of senior leaders’ awareness of their training/working experiences, listening to and acting on.ConclusionsActive and demonstrable CLSL plays a vital role in trainee doctors’ retention. It has both direct (through support) and indirect effects through improving trainee doctors’ PCF to reduce burnout and intention to quit. This seems particularly valuable among FY doctors. Implications for the development and management of the medical workforce are discussed.
Gabapentinoids for chemotherapy-induced peripheral neuropathy: systematic review and meta-analysis
Authors: Chang Tsung Wei , Yang Fu-Yu , Liu Yu-Chang , Hung Cheng-Hsien 
Published: June 2024

IntroductionChemotherapy-induced peripheral neuropathy (CIPN) affects patients’ quality of life and treatment effectiveness. Gabapentinoids, like gabapentin and pregabalin, are often used for CIPN treatment, but their efficacy and safety remain uncertain. This study reviews and analyses randomised controlled trial data on this topic.Materials/methodsWe searched PubMed, Embase and Cochrane CENTRAL until 29 August 2022 for studies on gabapentinoid use in CIPN. Meta-analysis was performed using RevMan V.5.4 and the Metafor package in R. Outcomes included pain scores, quality of life and adverse drug events.ResultsFor the prevention setting, our meta-analysis shows that pregabalin did not significantly improve average pain (standardised mean difference (SMD) −0.14, 95% CI −0.51 to 0.23; I2=26% (95% CI 0% to >98%)) or quality of life (mean difference (MD) 2.5, 95% CI −4.67 to 9.67; p=0.49) in preventing CIPN compared with placebo. However, it showed a potential trend towards reducing the worst pain (SMD −0.28, 95% CI −0.57 to 0.01; I2=0% (95% CI 0% to 98%; p=0.06)). For the treatment setting, some studies have shown a potential therapeutic effect of gabapentinoids. However, the results are not consistent between studies. Given the studies’ heterogeneity, a meta-analysis in treatment setting was not performed.ConclusionThere is limited evidence to support the use of gabapentinoids in CIPN. In prevention setting, gabapentinoids do not significantly prevent CIPN. In treatment setting, studies have been inconsistent in their conclusions, lacking definitive benefits over placebo. More comprehensive and higher quality research is needed in the future.PROSPERO registration numberCRD42022361193.
Regional hospice and palliative care networks worldwide: scoping review
Authors: Röwer Hanna A A , Herbst Franziska A , Schwabe Sven 
Published: June 2024

BackgroundRegional hospice and palliative care networks (RHPCNs) are increasingly being established to improve integrative care for patients with life-limiting illnesses. This scoping review aimed at identifying and synthesising international literature on RHPCNs, focusing on structures, outcomes, benefits, success factors and good practices.MethodFollowing Arksey and O’Malley’s (2005) framework, a search of four electronic databases (CINAHL, Google Scholar, PubMed, Web of Science Core Collection) was conducted on 7 July 2023. Additionally, a manual search of reference lists of the identified articles was performed. Original research, qualification theses and descriptive reports on RHPCNs at a structural level were included.FindingsTwo researchers analysed 777 article abstracts, screened 104 full texts and selected 24 articles. The included studies predominantly used qualitative designs. RHPCNs self-identify as local stakeholders, employ coordination offices and steering committees, and actively recruit network partners. Outcomes included improved professional practices, enhanced quality of care, increased patient utilisation of regional care offerings and improved patient transitions between care providers. Success factors included clear coordination, transparent communication, strategic planning and resource-securing strategies.ConclusionsThe analysis identified key RHPCN success factors such as effective communication and adaptive leadership. Despite the need for further research, the findings emphasise RHPCNs’ potential to improve palliative care and encourage policymaker support.OtherThis scoping review is part of the research project HOPAN, which aims at assessing and analysing RHPCNs in Germany. The project is funded by the German Innovation Fund of the Federal Joint Committee (G-BA) (Grant N° 01VSF22042; funding period: 01/2023–12/2024).
Generative models for simulation of KamLAND-Zen
Authors: Fu Zhenghao , Grant Christopher , Krawiec Dominika M. , Li Aobo , Winslow Lindley A. 
Published: June 2024

AbstractThe next generation of searches for neutrinoless double beta decay ($$0 \nu \beta \beta $$

0
ν
β
β

) are poised to answer deep questions on the nature of neutrinos and the source of the Universe’s matter–antimatter asymmetry. They will be looking for event rates of less than one event per ton of instrumented isotope per year. To claim discovery, accurate and efficient simulations of detector events that mimic $$0 \nu \beta \beta $$

0
ν
β
β

is critical. Traditional Monte Carlo (MC) simulations can be supplemented by machine-learning-based generative models. This work describes the performance of generative models that we designed for monolithic liquid scintillator detectors like KamLAND to produce accurate simulation data without a predefined physics model. We present their current ability to recover low-level features and perform interpolation. In the future, the results of these generative models can be used to improve event classification and background rejection by providing high-quality abundant generated data.
FRENA: India’s first nuclear astrophysics accelerator center
Authors: Banerjee Akashrup , Basu Chinmay 
Published: June 2024

AbstractTo address several outstanding problems in nuclear astrophysics, an accelerator centre has been developed in India. The Facility for Research in Experimental Nuclear Astrophysics (FRENA) will serve as a laboratory dedicated to nuclear astrophysics measurements. The 3 MV high current, low energy two-stage accelerator housed at FRENA is capable of delivering different types of beams—protons, alphas, carbon, silicon, among others. The accelerator can provide direct, as well as, pulsed beams of protons and alphas. A set of dedicated high efficiency detector arrays composed of solid state detectors, scintillation detectors and other particle detectors will be used at different end-stations to perform different experiments in the coming years.
Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma
Authors: Gonzalez-Kozlova Edgar , Huang Hsin-Hui , Jagede Opeyemi A. , Tuballes Kevin , Del Valle Diane M. , Kelly Geoffrey , Patel Manishkumar , Xie Hui , Harris Jocelyn , Argueta Kimberly , Nie Kai , Barcessat Vanessa , Moravec Radim , Altreuter Jennifer , Duose Dzifa Y. , Kahl Brad S. , Ansell Stephen M. , Yu Joyce , Cerami Ethan , Lindsay James R. , Wistuba Ignacio I. , Kim-Schulze Seunghee , Diefenbach Catherine S. , Gnjatic Sacha 
Published: June 2024

Abstract

To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (&gt;75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a durable increase in soluble PD1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV + N and BV + I + N) compared with BV + I (P &lt; 0.05). Nonresponders and patients with short progression-free survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine–deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (P &lt; 0.05). The results suggest a circulating tumor-immune-derived signature of BV ± I ± N treatment resistance that may be useful for patient stratification in combination checkpoint therapy.

Significance:
Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody–drug conjugate combinations with potential implications for treatment decisions in relapsed HL.
Loss of Smooth Muscle Tenascin-X Inhibits Vascular Remodeling Through Increased TGF-β Signaling
Authors: Liang Guozheng , Lv Xiao-Fei , Huang Wei , Jin Young-June , Roquid Kenneth Anthony , Kawase Haruya , Offermanns Stefan 
Published: June 2024

BACKGROUND:
Vascular smooth muscle cells (VSMCs) are highly plastic. Vessel injury induces a phenotypic transformation from differentiated to dedifferentiated VSMCs, which involves reduced expression of contractile proteins and increased production of extracellular matrix and inflammatory cytokines. This transition plays an important role in several cardiovascular diseases such as atherosclerosis, hypertension, and aortic aneurysm. TGF-β (transforming growth factor-β) is critical for VSMC differentiation and to counterbalance the effect of dedifferentiating factors. However, the mechanisms controlling TGF-β activity and VSMC phenotypic regulation under in vivo conditions are poorly understood. The extracellular matrix protein TN-X (tenascin-X) has recently been shown to bind TGF-β and to prevent it from activating its receptor.

METHODS:
We studied the role of TN-X in VSMCs in various murine disease models using tamoxifen-inducible SMC-specific knockout and adeno-associated virus–mediated knockdown.

RESULTS:

In hypertensive and high-fat diet–fed mice, after carotid artery ligation as well as in human aneurysmal aortae, expression of
Tnxb
, the gene encoding TN-X, was increased in VSMCs. Mice with smooth muscle cell–specific loss of TN-X (SMC-Tnxb-KO) showed increased TGF-β signaling in VSMCs, as well as upregulated expression of VSMC differentiation marker genes during vascular remodeling compared with controls. SMC-specific TN-X deficiency decreased neointima formation after carotid artery ligation and reduced vessel wall thickening during Ang II (angiotensin II)–induced hypertension. SMC-Tnxb-KO mice lacking ApoE showed reduced atherosclerosis and Ang II–induced aneurysm formation under high-fat diet. Adeno-associated virus–mediated SMC-specific expression of short hairpin RNA against
Tnxb
showed similar beneficial effects. Treatment with an anti-TGF-β antibody or additional SMC-specific loss of the TGF-β receptor reverted the effects of SMC-specific TN-X deficiency.

CONCLUSIONS:
In summary, TN-X critically regulates VSMC plasticity during vascular injury by inhibiting TGF-β signaling. Our data indicate that inhibition of vascular smooth muscle TN-X may represent a strategy to prevent and treat pathological vascular remodeling.
In Vivo Computed Tomography Sizing for Redo–Transcatheter Aortic Valve Replacement in Evolut Valves: Impact on Sizing, Feasibility, and Prosthesis-Patient Mismatch
Authors: Okada Atsushi , Fukui Miho , Zaid Syed , Thao Kiahltone R. , Walser-Kuntz Evan , Stanberry Larissa I. , Burns Marcus R. , Koike Hideki , Wang Cheng , Phichaphop Asa , Lesser John R. , Cavalcante João L. , Sorajja Paul , Bapat Vinayak N. 
Published: June 2024

BACKGROUND:
SAPIEN3 (S3) is a ubiquitous redo–transcatheter aortic valve (TAV) replacement alternative for degenerated Evolut valves, but S3 sizing for S3-in-Evolut remains unclear. We sought to compare the impact of in vivo computed tomography (CT)-sizing on redo-TAV feasibility for S3-in-Evolut with traditional bench-sizing.

METHODS:
CT scans of 290 patients treated using Evolut R/PRO/PRO+ between July 2015 and December 2021 were analyzed. S3-in-Evolut was simulated using S3 outflow/neoskirt plane (NSP) at node-6, -5, and -4. CT-sizing for S3 was determined by averaging 4 areas of the Evolut stent frame at NSP level and 3 nodes below. Redo-TAV was deemed feasible if the NSP was below the coronaries, or the narrowest valve (virtual S3)-to-aorta distance was >4 mm. Risk of prosthesis-patient mismatch was estimated using predicted indexed-effective orifice area.

RESULTS:

Compared with bench-sizing, CT-sizing yielded smaller S3 size in 82% at node-6, 81% at node-5, and 84% at node-4. Factors associated with CT-sizing less than bench-sizing were larger index Evolut size, underexpansion of index Evolut, and shallower implant depth (all
P
<0.05). CT-sizing increased redo-TAV feasibility by +8% at node-6, +10% at node-5, and +4% at node-4. Redo-TAV feasibility increased with annulus size, sinotubular junction dimensions, coronary heights, index Evolut size, deeper Evolut implant depth, and lower NSP levels (all
P
<0.05). CT-sizing had a slightly higher estimated risk of severe prosthesis-patient mismatch (9% at node-6, 7% at node-5, and 6% at node-4), which could be mitigated by changing the NSP.

CONCLUSIONS:
CT-sizing for S3-in-Evolut is associated with higher feasibility of redo-TAV compared with bench-sizing, potentially reducing the risk of excessive oversizing and S3 underexpansion. Further validation using real-world clinical data is necessary.
Monoclonal Antibody chP3R99 Reduces Subendothelial Retention of Atherogenic Lipoproteins in Insulin‐Resistant Rats: Acute Treatment Versus Long‐Term Protection as an Idiotypic Vaccine for Atherosclerosis
Authors: Soto Yosdel , Hernández Arletty , Sarduy Roger , Brito Victor , Marleau Sylvie , Vine Donna F. , Vázquez Ana M. , Proctor Spencer D. 
Published: June 2024

BACKGROUND
Atherosclerosis is triggered by the retention of apolipoprotein B‐containing lipoproteins by proteoglycans. In addition to low‐density lipoprotein, remnant lipoproteins have emerged as pivotal contributors to this pathology, particularly in the context of insulin resistance and diabetes. We have previously reported antiatherogenic properties of a monoclonal antibody (chP3R99) that recognizes sulfated glycosaminoglycans on arterial proteoglycans.

METHODS AND RESULTS

Solid‐phase assays demonstrated that chP3R99 effectively blocked >50% lipoprotein binding to chondroitin sulfate and vascular extracellular matrix in vitro. The preperfusion of chP3R99 (competitive effect) resulted in specific antibody‐arterial accumulation and reduced fluorescent lipoprotein retention by ~60% in insulin resistant JCR:LA‐
cp
rats. This competitive reduction was dose dependent (25–250 μg/mL), effectively decreasing deposition of cholesterol associated with lipoproteins. In a 5‐week vaccination study in insulin resistant rats with (200 μg subcutaneously, once a week), chP3R99 reduced arterial lipoprotein retention, and was associated with the production of antichondroitin sulfate antibodies (Ab3) able to accumulate in the arteries (dot‐blot). Neither the intravenous inoculation of chP3R99 (4.5 mg/kg), nor the immunization with this antibody displayed adverse effects on lipid or glucose metabolism, insulin resistance, liver function, blood cell indices, or inflammation pathways in JCR:LA
‐cp
rats.

CONCLUSIONS
Both acute (passive) and long‐term administration (idiotypic cascade) of chP3R99 antibody reduced low‐density lipoprotein and remnant lipoprotein interaction with proteoglycans in an insulin‐resistant setting. These findings support the innovative approach of targeting proatherogenic lipoprotein retention by chP3R99 as a passive therapy or as an idiotypic vaccine for atherosclerosis.
Preoperative Malnutrition Increases Risk of In‐Hospital Mortality, Major Infection, and Longer Intensive Care Unit Stay After Ventricular Septal Defect Closure
Authors: Wittenberg Rachel E. , Gauvreau Kimberlee , Duggan Christopher P. , Du Xinwei , Giang Do , Jayanthi Kishore , Sandoval Nestor , Sivalingam Sivakumar , Zhao Xiaolei , Jenkins Kathy J. 
Published: June 2024

Background
High energy requirements and poor feeding can lead to growth failure in patients with ventricular septal defect (VSD), but effects of preoperative malnutrition on surgical outcomes are poorly understood, especially in low‐resource settings.

Methods and Results

We analyzed a cohort of children <5 years of age undergoing VSD closure at 60 global centers participating in the International Quality Improvement Collaborative for Congenital Heart Disease, 2015 to 2020. We calculated adjusted odds ratios (ORs) for in‐hospital death and major infection and adjusted coefficients for duration of intensive care unit stay for 4 measures of malnutrition: severe wasting (weight‐for‐height
Z
score, <−3), moderate wasting (−3<weight‐for‐height
Z
score≤−2), underweight (weight‐for‐age
Z
score, ≤−2), and stunting (height‐for‐age
Z
score, ≤−2) according to World Health Organization Child Growth Standards. Among 10 966 children undergoing VSD closure in the analyzed cohort, 8136 (74%) were membranous VSDs. Median age was 9.6 months (interquartile range, 3.6–12.0), and 4088 (37.3%) had wasting/severe wasting, 5029 (45.9%) had underweight, and 3515 (32.1%) had stunting. There were 4749 (43.3%) children who met the criteria for ≥2 malnutrition categories. Overall, 84 patients (0.8%) died in‐hospital, and 199 (1.8%) had major infection. Severe wasting (OR, 3.38 [95% CI, 1.55–7.35];
P
=0.002), underweight (OR, 6.46 [95% CI, 2.81–14.8];
P
<0.001), and stunting (OR, 2.73 [95% CI, 1.40–5.34];
P
=0.003) were independent predictors of mortality. Similar results were observed for infection and duration of intensive care unit stay. Underweight was the strongest predictor of adverse outcomes. Children meeting criteria for all 3 (stunting, wasting, and underweight) had 17.2 times higher odds of mortality (
P
<0.001) than nonmalnourished children.

Conclusions
Malnutrition was associated with mortality, infection, and longer intensive care unit stay in a global cohort of children undergoing VSD closure.
Postpartum Weight Change Association With Readmission and Blood Pressure Trend Among Individuals With Hypertensive Disorders of Pregnancy
Authors: Lemon Lara S. , Venkatakrishnan Kripa , Countouris Malamo , Simhan Hyagriv , Hauspurg Alisse 
Published: June 2024

Background
The aim of this study was to evaluate the association between early postpartum weight change and (1) hospital readmission and (2) 2‐week blood pressure trajectory.

Methods and Results
This retrospective study cohort included 1365 individuals with a hypertensive disorder of pregnancy enrolled in a postpartum hypertension remote monitoring program. Exposure was percentage weight change from delivery to first weight recorded within 10 days postpartum. We first modeled likelihood of hospital readmission within 8 weeks postpartum using logistic regression adjusting for age, race, insurance, type of hypertensive disorder of pregnancy, early body mass index, gestational weight gain, mode of delivery, and any discharge antihypertensive medications. We then performed case–control analysis additionally matching in a 1:3 ratio on breastfeeding, early body mass index, discharge on antihypertensive medications, and days between weight measurements. Both analytic approaches were repeated, limiting to readmissions attributable to hypertension or heart failure. Finally, we compared blood pressure trajectories over first 2 weeks postpartum. Individuals who did not lose weight in the early postpartum period had more admissions compared with weight loss groups (group 3: 14.1% versus group 2: 5.8% versus group 1: 4.5%). These individuals had 4 times the odds of postpartum readmissions (adjusted odds ratio [aOR], 3.9 [95% CI, 1.8–8.6]) to 7 (aOR, 7.8 [95% CI, 2.3–26.5]) compared with those with the most weight loss. This association strengthened when limited to hypertension or heart failure readmissions. These individuals also had more adverse postpartum blood pressure trajectories, with significant differences by weight change group.

Conclusions
Weight change is readily accessible and may identify individuals at high risk for postpartum readmission following a hypertensive disorder of pregnancy who could benefit from targeted interventions.
Survival and Neurologic Outcomes From Pharmacologic Peptide Administration During Cardiopulmonary Resuscitation of Pulseless Electrical Activity
Authors: Oberdier Matt T. , Li Jing , Ambinder Daniel I. , Suzuki Masahito , Tumarkin Ethan , Fink Sarah , Neri Luca , Zhu Xiangdong , Justice Cody N. , Vanden Hoek Terry L. , Halperin Henry R. 
Published: June 2024

Background
Outcomes from cardiopulmonary resuscitation (CPR) following sudden cardiac arrest are suboptimal. Postresuscitation targeted temperature management has been shown to have benefit in subjects with sudden cardiac arrest due to ventricular fibrillation, but there are few data for outcomes from sudden cardiac arrest due to pulseless electrical activity. In addition, intra‐CPR cooling is more effective than postresuscitation cooling. Physical cooling is associated with increased protein kinase B activity. Therefore, our group developed a novel peptide, TAT‐PHLPP9c, which regulates protein kinase B. We hypothesized that when given during CPR, TAT‐PHLPP9c would improve survival and neurologic outcomes following pulseless electrical activity arrest.

Methods and Results

In 24 female pigs, pulseless electrical activity was induced by inflating balloon catheters in the right coronary and left anterior descending arteries for ≈7 minutes. Advanced life support was initiated. In 12 control animals, epinephrine was given after 1 and 3 minutes. In 12 peptide‐treated animals, 7.5 mg/kg TAT‐PHLPP9c was also administered at 1 and 3 minutes of CPR. The balloons were removed after 2 minutes of support. Animals were recovered and neurologically scored 24 hours after return of spontaneous circulation. Return of spontaneous circulation was more common in the peptide group, but this difference was not significant (8/12 control versus 12/12 peptide;
P
=0.093), while fully intact neurologic survival was significantly more common in the peptide group (0/12 control versus 11/12 peptide;
P
<0.00001). TAT‐PHLPP9c significantly increased myocardial nicotinamide adenine dinucleotide levels.

Conclusions
TAT‐PHLPP9c resulted in improved survival with full neurologic function after sudden cardiac arrest in a swine model of pulseless electrical activity, and the peptide shows potential as an intra‐CPR pharmacologic agent.