bluuebunny/crossref_metadata_2025_split huggingface dataset:
Workplace interventions to improve well-being and reduce burnout for nurses, physicians and allied healthcare professionals: a systematic review
Authors: Cohen Catherine , Pignata Silvia , Bezak Eva , Tie Mark , Childs Jessie 
Published: June 2023

There is a growing need for interventions to improve well-being in healthcare workers, particularly since the onset of COVID-19.ObjectivesTo synthesise evidence since 2015 on the impact of interventions designed to address well-being and burnout in physicians, nurses and allied healthcare professionals.DesignSystematic literature review.Data sourcesMedline, Embase, Emcare, CINAHL, PsycInfo and Google Scholar were searched in May–October 2022.Eligibility criteria for selecting studiesStudies that primarily investigated burnout and/or well-being and reported quantifiable preintervention and postintervention outcomes using validated well-being measures were included.Data extraction and synthesisFull-text articles in English were independently screened and quality assessed by two researchers using the Medical Education Research Study Quality Instrument. Results were synthesised and presented in both quantitative and narrative formats. Meta-analysis was not possible due to variations in study designs and outcomes.ResultsA total of 1663 articles were screened for eligibility, with 33 meeting inclusion criterium. Thirty studies used individually focused interventions, while three were organisationally focused. Thirty-one studies used secondary level interventions (managed stress in individuals) and two were primary level (eliminated stress causes). Mindfulness-based practices were adopted in 20 studies; the remainder used meditation, yoga and acupuncture. Other interventions promoted a positive mindset (gratitude journaling, choirs, coaching) while organisational interventions centred on workload reduction, job crafting and peer networks. Effective outcomes were reported in 29 studies, with significant improvements in well-being, work engagement, quality of life and resilience, and reductions in burnout, perceived stress, anxiety and depression.ConclusionThe review found that interventions benefitted healthcare workers by increasing well-being, engagement and resilience, and reducing burnout. It is noted that the outcomes of numerous studies were impacted by design limitations that is, no control/waitlist control, and/or no post intervention follow-up. Suggestions are made for future research.
Effects of non-invasive brain stimulation for degenerative cerebellar ataxia: a protocol for a systematic review and meta-analysis
Authors: Matsugi Akiyoshi , Ohtsuka Hiroyuki , Bando Kyota , Kondo Yuki , Kikuchi Yutaka 
Published: June 2023

IntroductionTo date, the medical and rehabilitation needs of people with degenerative cerebellar ataxia (DCA) are not fully met because no curative treatment has yet been established. Movement disorders such as cerebellar ataxia and balance and gait disturbance are common symptoms of DCA. Recently, non-invasive brain stimulation (NIBS) techniques, including repetitive transcranial magnetic stimulation and transcranial electrical stimulation, have been reported as possible intervention methods to improve cerebellar ataxia. However, evidence of the effects of NIBS on cerebellar ataxia, gait ability, and activity of daily living is insufficient. This study will aim to systematically evaluate the clinical effects of NIBS on patients with DCA.Methods and analysisWe will conduct a preregistered systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We will include randomised controlled trials to assess the effects of NIBS on patients with DCA. The primary clinical outcome will be cerebellar ataxia, as measured by the Scale for Assessment and Rating of Ataxia and the International Cooperative Ataxia Rating Scale. The secondary outcomes will include gait speed, functional ambulatory capacity and functional independence measure, as well as any other reported outcomes that the reviewer considers important. The following databases will be searched: PubMed, Cochrane Central Register of Controlled Trials, CINAHL and PEDro. We will assess the strength of the evidence included in the studies and estimate the effects of NIBS.Ethics and disseminationBecause of the nature of systematic reviews, no ethical issues are anticipated. This systematic review will provide evidence on the effects of NIBS in patients with DCA. The findings of this review are expected to contribute to clinical decision-making towards selecting NIBS techniques for treatment and generating new clinical questions to be addressed.PROSPERO registration numberCRD42023379192.
Predictive value of clinician impression for readmission and postdischarge mortality among neonates and young children in Dar es Salaam, Tanzania and Monrovia, Liberia
Authors: Rees Chris A , Kisenge Rodrick , Ideh Readon C , Kamara Julia , Coleman Ye-Jeung , Samma Abraham , Godfrey Evance , Manji Hussein K , Sudfeld Christopher R , Westbrook Adrianna L , Niescierenko Michelle , Morris Claudia R , Whitney Cynthia G , Breiman Robert F , Manji Karim P , Duggan Christopher P 
Published: June 2023

BackgroundThere are no validated clinical decision aids to identify neonates and young children at risk of hospital readmission or postdischarge mortality in sub-Saharan Africa, leaving the decision to discharge a child to a clinician’s impression. Our objective was to determine the precision of clinician impression to identify neonates and young children at risk for readmission and postdischarge mortality.MethodsWe conducted a survey study nested in a prospective observational cohort of neonates and children aged 1–59 months followed 60 days after hospital discharge from Muhimbili National Hospital in Dar es Salaam, Tanzania or John F. Kennedy Medical Center in Monrovia, Liberia. Clinicians who discharged each enrolled patient were surveyed to determine their perceived probability of the patient’s risk of 60-day hospital readmission or postdischarge mortality. We calculated the area under the precision-recall curve (AUPRC) to determine the precision of clinician impression for both outcomes.ResultsOf 4247 discharged patients, 3896 (91.7%) had available clinician surveys and 3847 (98.7%) had 60-day outcomes available: 187 (4.8%) were readmitted and 120 (3.1%) died within 60 days of hospital discharge. Clinician impression had poor precision in identifying neonates and young children at risk of hospital readmission (AUPRC: 0.06, 95% CI: 0.04 to 0.08) and postdischarge mortality (AUPRC: 0.05, 95% CI: 0.03 to 0.08). Patients for whom clinicians attributed inability to pay for future medical treatment as the reason for risk for unplanned hospital readmission had 4.76 times the odds hospital readmission (95% CI: 1.31 to 17.25, p=0.02).ConclusionsGiven the poor precision of clinician impression alone to identify neonates and young children at risk of hospital readmission and postdischarge mortality, validated clinical decision aids are needed to aid in the identification of young children at risk for these outcomes.
Relationship between psychological distress, health behaviours and future reports of hypertension among adults in East Zimbabwe: a cohort study
Authors: Shamsuddin Shehla , Davis Katherine , Moorhouse Louisa , Mandizvidza Phyllis , Maswera Rufurwokuda , Dadirai Tawanda , Nyamukapa Constance , Gregson Simon , Chigogora Sungano 
Published: June 2023

IntroductionExtensive cross-sectional evidence has demonstrated an association between psychological distress (PD) and hypertension. However, evidence on the temporal relationship is limited, especially in low-income and middle-income countries. The role of health risk behaviours including smoking and alcohol consumption in this relationship is also largely unknown. The aim of this study was to investigate the association between PD and later development of hypertension, and how this association may have been influenced by health risk behaviours, among adults in east Zimbabwe.MethodsThe analysis included 742 adults (aged 15–54 years) recruited by the Manicaland general population cohort study, who did not have hypertension at baseline in 2012–2013, and who were followed until 2018-2019. In 2012–2013, PD was measured using the Shona Symptom Questionnaire, a screening tool validated for use in Shona-speaking countries including Zimbabwe (cut-off point: 7). Smoking, alcohol consumption and use of drugs (health risk behaviours) were also self-reported. In 2018-2019, participants reported if they had diagnosed with hypertension by a doctor or nurse. Logistic regression was used to assess the association between PD and hypertension.ResultsIn 2012, 10.4% of the participants had PD. The odds of new reports of hypertension were 2.04 times greater (95% CI 1.16 to 3.59) among those with PD at baseline, after adjusting for sociodemographic and health risk behaviour variables. Female gender (adjusted odds ratio, AOR 6.89, 95% CI 2.71 to 17.53), older age (AOR 2.67, 95% CI 1.63 to 4.42), and greater wealth (AOR 2.10, 95% CI 1.04 to 4.24 more wealthy, 2.88, 95% CI 1.24 to 6.67 most wealthy) were significant risk factors for hypertension. The AOR for the relationship between PD and hypertension did not differ substantially between models with and without health risk behaviours.ConclusionPD was associated with an increased risk of later reports of hypertension in the Manicaland cohort. Integrating mental health and hypertension services within primary healthcare may reduce the dual burden of these non-communicable diseases.
Measuring the Hubble constant with cosmic chronometers: a machine learning approach
Authors: Bengaly Carlos , Dantas Maria Aldinez , Casarini Luciano , Alcaniz Jailson 
Published: June 2023

AbstractLocal measurements of the Hubble constant ($$H_0$$

H
0

) based on Cepheids e Type Ia supernova differ by $$\approx 5 \sigma $$

≈
5
σ

from the estimated value of $$H_0$$

H
0

from Planck CMB observations under $$\Lambda $$
Λ
CDM assumptions. In order to better understand this $$H_0$$

H
0

tension, the comparison of different methods of analysis will be fundamental to interpret the data sets provided by the next generation of surveys. In this paper, we deploy machine learning algorithms to measure the $$H_0$$

H
0

through a regression analysis on synthetic data of the expansion rate assuming different values of redshift and different levels of uncertainty. We compare the performance of different regression algorithms as Extra-Trees, Artificial Neural Network, Gradient Boosting, Support Vector Machines, and we find that the Support Vector Machine exhibits the best performance in terms of bias-variance tradeoff in most cases, showing itself a competitive cross-check to non-supervised regression methods such as Gaussian Processes.
Spectral-luminescence, redox and photochemical properties of AlIII, GaIII and InIII complexes formed by peripherally chlorinated phthalocyanines and tetrapyrazinoporphyrazines
Authors: Finogenov Daniil N. , Lazovskiy Dmitriy A. , Kopylova Alina S. , Zhabanov Yuriy A. , Stuzhin Pavel A. 
Published: June 2023

Complexes of Al[Formula: see text], Ga[Formula: see text] and In[Formula: see text] with peripherally chlorinated phthalocyanine (Cl8PcM) and tetrapyrazinoporphyrazine (Cl8TPyzM) were prepared and studied using spectral and electrochemical methods. DFT calculations were used to reveal the peculiarities of their molecular and electronic structure. Peripheral chlorination of phthalocyanine complexes increases their electron affinity and the first reduction of [Cl8PcM] is observed at −0.25 – −0.35 V (by 0.2 – 0.3 V easier than for [PcM]). Additional azasubstitution further increases the acceptor properties of the macrocycle and [Cl8TPyzM] are reduced at −0.16 V. Among [Cl8PcM] only the Ga[Formula: see text] complex is stable to photooxidation, while among [Cl8TPyzPzM] it is the only one undergoing photoreduction. Fluorescence quantum yields ([Formula: see text] and lifetimes ([Formula: see text] as well as the ability to generate singlet oxygen ([Formula: see text] were determined. The [Formula: see text] values show typical dependence on the central metal Al > Ga >> In and are decreased upon the introduction of chlorine atoms in the peripheral and especially in the axial position. At the same time, azasubstitution in the benzene ring has a minor influence on the [Formula: see text] values but strongly shortens [Formula: see text] (from ca 6 to ca 2 ns). The Ga[Formula: see text] complexes have the highest ability to generate 1O2 and can be considered as effective photosensitizers, especially [Cl8TPyzPzGa(OH)] ([Formula: see text] = 0.87 in slightly acidified solution). Spectral properties in a strongly acid medium were also studied and it was observed that [Cl8PcM] are consequently protonated on meso-nitrogens.
De Novo and Histologically Transformed Small-Cell Lung Cancer Is Sensitive to Lurbinectedin Treatment Through the Modulation of EMT and NOTCH Signaling Pathways
Authors: Chakraborty Subhamoy , Coleman Charles , Manoj Parvathy , Demircioglu Deniz , Shah Nisargbhai , de Stanchina Elisa , Rudin Charles M. , Hasson Dan , Sen Triparna 
Published: June 2023

Abstract

Purpose:
Small-cell lung cancer (SCLC) is a high-grade neuroendocrine tumor with dismal prognosis and limited treatment options. Lurbinectedin, conditionally approved as a second-line treatment for metastatic SCLC, drives clinical responses in about 35% of patients, and the overall survival (OS) of those who benefit from it remains very low (∼9.3 months). This finding highlights the need to develop improved mechanistic insight and predictive biomarkers of response.

Experimental Design:
We used human and patient-derived xenograft (PDX)-derived SCLC cell lines to evaluate the effect of lurbinectedin in vitro. We also demonstrate the antitumor effect of lurbinectedin in multiple de novo and transformed SCLC PDX models. Changes in gene and protein expression pre- and post-lurbinectedin treatment was assessed by RNA sequencing and Western blot analysis.

Results:
Lurbinectedin markedly reduced cell viability in the majority of SCLC models with the best response on POU2F3-driven SCLC cells. We further demonstrate that lurbinectedin, either as a single agent or in combination with osimertinib, causes an appreciable antitumor response in multiple models of EGFR-mutant lung adenocarcinoma with histologic transformation to SCLC. Transcriptomic analysis identified induction of apoptosis, repression of epithelial–mesenchymal transition, modulation of PI3K/AKT, NOTCH signaling associated with lurbinectedin response in de novo, and transformed SCLC models.

Conclusions:
Our study provides a mechanistic insight into lurbinectedin response in SCLC and the first demonstration that lurbinectedin is a potential therapeutic target after SCLC transformation.
Results of an Open-label, Phase Ia/b Study of Pembrolizumab plus Olaratumab in Patients with Unresectable, Locally Advanced, or Metastatic Soft-Tissue Sarcoma
Authors: Schöffski Patrick , Bahleda Rastislav , Wagner Andrew J. , Burgess Melissa A. , Junker Niels , Chisamore Michael , Peterson Patrick , Szpurka Anna M. , Ceccarelli Matteo , Tap William D. 
Published: June 2023

Abstract

Purpose:
The study evaluated safety and efficacy of olaratumab + pembrolizumab in patients with unresectable locally advanced/metastatic soft-tissue sarcoma (STS) with disease progression on standard treatment.

Patients and Methods:
This was open-label, multicenter, nonrandomized, phase Ia/Ib dose-escalation study followed by cohort expansion (olaratumab + pembrolizumab intravenous infusion). Primary objectives were safety and tolerability.

Results:
The majority of patients enrolled (n = 41) were female [phase Ia: 9 of 13, phase Ib/dose-expansion cohort (DEC), 17 of 28], aged &lt; 65 years. In phases Ia and Ib, 13 and 26 patients received prior systemic therapy, respectively. Patients received olaratumab 15 mg/kg (phase Ia; cohort 1) or 20 mg/kg (phase Ia; cohort 2 and phase Ib) and pembrolizumab 200 mg (phase Ia/Ib). The median (Q1–Q3) duration of therapy (olaratumab) was 6.0 (3.0–11.9; cohort 1), 14.4 (12.4–20.9; cohort 2), and 14.0 (6.0–21.8) weeks (DEC). No dose-limiting toxicities and few grade ≥ 3 treatment-emergent adverse events [TEAE; 15 mg/kg: 2 (increased lipase); 20 mg/kg: 1 (increased lipase), 1 (colitis), 2 (diarrhea), 3 (anemia)] were reported. Two TEAEs (increased lipase) were related to study discontinuations. Twenty-one patients reported mild (grade ≤ 2) TEAEs [phase Ia, disease control rate (DCR):14.3% (1/7, cohort 1); 66.7% (4/6, cohort 2); no responses were reported; phase Ib, DCR: 53.6% (15/28); objective response rate: 21.4% (6/28; RECIST and irRECIST criteria)]. No response was observed in patients with programmed death ligand-1–positive tumors.

Conclusions:
Antitumor activity was observed in some patients in DEC, and combination was well tolerated with manageable safety profile. Further studies are warranted to evaluate the efficacy and mechanistic impact of platelet-derived growth factor receptor inhibitors with immune checkpoint modulator coadministration.
Salvage Ipilimumab plus Nivolumab after Anti-PD-1/PD-L1 Therapy in Advanced Hepatocellular Carcinoma
Authors: Alden Stephanie L. , Lim Mir , Kao Chester , Shu Daniel , Singal Amit G. , Noonan Anne , Griffith Paige , Baretti Marina , Ho Won Jin , Kamel Ihab , Yarchoan Mark , Hsiehchen David 
Published: June 2023

Combination anti-PD-(L)1/CTLA-4 blockade is approved in patients with hepatocellular carcinoma (HCC) in the first-line setting or after sorafenib, but whether this treatment has efficacy after prior anti-PD-(L)1 therapy is unknown. We performed a multicenter retrospective review of patients with advanced HCC treated with ipilimumab plus nivolumab after prior anti-PD-(L)1 therapy, excluding patients with prior anti-CTLA-4 treatment. Of the 32 patients who met our inclusion criteria, prior anti-PD-(L)1 regimens included atezolizumab plus bevacizumab (50%, n = 16), other anti-VEGF plus anti-PD-(L)1 combinations (31%, n = 10), and anti-PD-(L)1 monotherapy (19%, n = 6). The median number of prior systemic therapies was 2 (range, 1–8). The objective response rate with ipilimumab plus nivolumab by RECIST 1.1 was 22% [1 complete response (3%), 6 partial response (19%), 8 stable disease (25%), 16 progressive disease (50%), and 1 not evaluable (NE) (3%)], and objective response was associated with improved progression-free survival and overall survival. Immune-related adverse events were reported in 13 patients (41%), with no new safety signals. This study demonstrates that ipilimumab plus nivolumab has efficacy in patients with HCC who have received prior anti-PD-(L)1 therapy, suggesting that failure to respond to prior PD-(L)1 blockade should not preclude treatment with salvage ipilimumab plus nivolumab. Prospective studies are needed to define the optimal sequence of therapies.

Significance:
Anti-PD-(L)1 containing regimens are the preferred first-line treatment for advanced HCC, but whether salvage with PD-(L)1/CTLA-4 blockade is effective in patients who have failed prior anti-PD-(L)1 therapy is unknown. Our study demonstrates that ipilimumab plus nivolumab has clinical activity in patients with advanced HCC previously treated with anti-PD-(L)1 therapy, supporting the continued use of this regimen in the late-line setting after prior anti-PD-(L)1 exposure.
Vitamin D Receptor From VSMCs Regulates Vascular Calcification During CKD: A Potential Role for miR-145a
Authors: Caus Maite , Alonso-Montes Cristina , Fernandez-Martin Jose Luis , Marti-Antonio Manuel , Bozic Milica , Valdivielso Jose M. 
Published: June 2023

BACKGROUND:
Vascular calcification (VC) is a highly prevalent complication of chronic kidney disease (CKD) and is associated with the higher morbidity-mortality of patients with CKD. VDR (vitamin D receptor) has been proposed to play a role in the osteoblastic differentiation of vascular smooth muscle cells (VSMCs), but the involvement of vitamin D in VC associated to CKD is controversial. Our aim was to determine the role of local vitamin D signaling in VSMCs during CKD-induced VC.

METHODS:
We used epigastric arteries from CKD-affected patients and individuals with normal renal function, alongside an experimental model of CKD-induced VC in mice with conditional deletion of VDR in VSMC. In vitro, experiments in VSMC with or without VDR incubated in calcification media were also used.

RESULTS:

CKD-affected patients and mice with CKD showed an increase in VC, together with increased arterial expression of VDR compared with controls with normal renal function. Conditional gene silencing of VDR in VSMCs led to a significant decrease of VC in the mouse model of CKD, despite similar levels of renal impairment and serum calcium and phosphate levels. This was accompanied by lower arterial expression of OPN (osteopontin) and lamin A and higher expression of SOST (sclerostin). Furthermore, CKD-affected mice showed a reduction of miR-145a expression in calcified arteries, which was significantly recovered in animals with deletion of VDR in VSMC. In vitro, the absence of VDR prevented VC, inhibited the increase of OPN, and reestablished the expression of miR-145a. Forced expression of miR-145a in vitro in VDR
wt
VSMCs blunted VC and decreased OPN levels.

CONCLUSIONS:
Our study provides evidence proving that inhibition of local VDR signaling in VSMCs could prevent VC in CKD and indicates a possible role for miR-145a in this process.
Activation of Platelet mTORC2/Akt Pathway by Anti-β2GP1 Antibody Promotes Thrombosis in Antiphospholipid Syndrome
Authors: Tang Zihan , Shi Hui , Chen Changming , Teng Jialin , Dai Jing , Ouyang Xinxing , Liu Honglei , Hu Qiongyi , Cheng Xiaobing , Ye Junna , Su Yutong , Sun Yue , Pan Haoyu , Wang Xuefeng , Liu Junling , Su Bing , Yang Chengde , Xu Yanyan , Liu Tingting 
Published: June 2023

BACKGROUND:
Anti-β2GP1 (β2-glycoprotein 1) antibodies are the primary pathogenic antibody to promote thrombosis in antiphospholipid syndrome (APS), yet the underlying mechanism remains obscure. We aimed to explore the intracellular pathway that mediated platelet activation.

METHODS:

Platelets were isolated from patients with APS and subjected to RNA sequencing. Platelet aggregation, the release of platelet granules, platelet spreading, and clot retraction were detected to evaluate platelet activation. We purified anti-β2GP1 antibodies from patients with APS and the total IgG from healthy donors to stimulate platelets with/without FcγRIIA (Fcγ receptor IIA) blocking antibody or Akt (protein kinase B) inhibitor. Platelet-specific
Sin1
(stress-activated protein kinase–interacting protein) deficiency mice were established. The thrombus model of inferior vena cava flow restriction, ferric chloride–induced carotid injury model, and laser-induced vessel wall injury in cremaster arterioles model were constructed after administration of anti-β2GP1 antibodies.

RESULTS:

Combined RNA sequencing and bioinformatics analysis suggested that APS platelets exhibited increased levels of mRNA associated with platelet activation, which was in line with the hyperactivation of APS platelets in response to stimuli. Platelet activation in APS platelets was accompanied by upregulation of the mTORC2 (mammalian target of the rapamycin complex 2)/Akt pathway and increased levels of SIN1 phosphorylation at threonine 86. Anti-β2GP1 antibody derived from patients with APS enhanced platelet activation and upregulated the mTORC2/Akt pathway. Moreover, the Akt inhibitor weakened the potentiating effect of the anti-β2GP1 antibody on platelet activation. Notably,
Sin1
deficiency suppresses anti-β2GP1 antibody–enhanced platelet activation in vitro and thrombosis in all 3 models.

CONCLUSIONS:
This study elucidated the novel mechanism involving the mTORC2/Akt pathway, which mediates the promotion of platelet activation and induction of thrombosis by the anti-β2GP1 antibody. The findings suggest that SIN1 may be a promising therapeutic target for the treatment of APS.