bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing cardiometabolic parameter monitoring in inpatients taking a second-generation antipsychotic: The CAMI-SGA study – a cross-sectional study
Authors: Fontaine Jennifer , Chin Evelyn , Provencher Jean-François , Rainone Anthony , Wazzan Dana , Roy Carmella , Rej Soham , Lordkipanidze Marie , Dagenais-Beaulé Vincent 
Published: April 2022

ObjectivesThis study aims to determine the proportion of initial cardiometabolic assessment and its predicting factors in adults with schizophrenia, bipolar disorder or other related diagnoses for whom a second-generation antipsychotic was prescribed in the hospital setting.DesignCross-sectional study.SettingThe psychiatry unit of a Canadian tertiary care teaching hospital in Montreal, Canada.Participants402 patients with aforementioned disorders who initiated, restarted or switched to one of the following antipsychotics: clozapine, olanzapine, risperidone, paliperidone or quetiapine, between 2013 and 2016.Primary outcome measuresWe assessed the proportion of cardiometabolic parameters monitored.Secondary outcome measuresWe identified predictors that influence the monitoring of cardiometabolic parameters and we assessed the proportion of adequate interventions following the screening of uncontrolled blood pressure and fasting glucose or glycated haemoglobin (HbA1c) results.ResultsOnly 37.3% of patients received monitoring for at least three cardiometabolic parameters. Blood pressure was assessed in 99.8% of patients; lipid profile in 24.4%; fasting glucose or HbA1c in 33.3% and weight or body mass index in 97.8% of patients while waist circumference was assessed in 4.5% of patients. For patients with abnormal blood pressure and glycaemic values, 42.3% and 41.2% subsequent interventions were done, respectively. The study highlighted the psychiatric diagnosis (substance induced disorder OR 0.06 95% CI 0.00 to 0.44), the presence of a court-ordered treatment (OR 0.79 95% CI 0.35 to 1.79) and the treating psychiatrist (up to OR 34.0 95% CI 16.2 to 140.7) as predictors of cardiometabolic monitoring.ConclusionsThis study reports suboptimal baseline cardiometabolic monitoring of patients taking an antipsychotic in a Canadian hospital. Optimising collaboration within a multidisciplinary team may increase cardiometabolic monitoring.
Musculoskeletal health climate is associated with musculoskeletal pain and sickness absence among workers: a cross-sectional study
Authors: Christiansen David Høyrup , Nielsen Kent Jacob , Andersen Dorte Raaby , Andersen Johan Hviid 
Published: April 2022

ObjectivesThis study aimed to investigate whether a musculoskeletal health climate, expressing the shared perceptions among workers concerning musculoskeletal health, is associated with number of musculoskeletal pain sites and sickness absence.DesignCross-sectional study.SettingSix slaughterhouses from 2 companies in Denmark and 6 home-nursing units and 12 nursing homes from 1 municipality in Jutland, Denmark.ParticipantsA total of 1092 slaughter house workers and 410 care workers completed an online questionnaire from February to October 2019.Outcome measuresThe exposure variable was musculoskeletal health climate assessed by two domains; (1) perceived management priority of musculoskeletal health measured by a modified subscale from the Nordic Safety Climate Questionnaire and (2) work group pain acceptance which was a modified version of the activity engagement subscale of the chronic pain acceptance scale. Outcomes variables were number of musculoskeletal pain sites (0–6) and days with sickness absence.ResultsThe associations between the two subscales, number of musculoskeletal pain sites and sickness absence were calculated using mixed linear and generalised estimating equation regression models. Higher perceived management priority scores were associated with a lower number of musculoskeletal pain sites across both job groups: β=-.57 (95% CI −0.91 to −0.23) and sickness absence (>5 days) due to musculoskeletal pain prevalence ratio (PR) 0.79 (95% CI 0.57 to 1.08). In contrast higher work group pain acceptance scores were associated with higher number of musculoskeletal pain sites: β=0.38 (0.11 to 0.66), whereas associations with sickness absences seemed to be modified by job groups; PR 1.59 care workers and PR 0.86 slaughterhouse workers.ConclusionThe observed relationship between musculoskeletal health climate, musculoskeletal pain sites and sickness absence indicate that cultural factors should receive increased attention in work place preventive interventions.
Gender and tobacco epidemic in South Korea: implications from age-period-cohort analysis and the DPSEEA framework
Authors: Kim Sera , Byun Garam , Jo Garam , Park Dahyun , Cho Sung-Il , Oh Hannah , Kim Rockli , Subramanian S V , Yun Sungha , Oh Kyungwon , Lee Jong-Tae , Shin Min-Jeong 
Published: April 2022

ObjectivesTo understand a 20-year trend of gender-specific smoking prevalence among adults in South Korea.DesignAge-period-cohort analysis using the intrinsic estimator method was applied to examine the separate contribution of age, period and cohort effect on smoking prevalence. The Driving Force-Pressure-State-Exposure-Effect-Action (DPSEEA) framework was used to explain the observed smoking trends by mapping potential determinants and to address policy implications.SettingGeneral adult population in South Korea.Participants34 828 men and 43 632 women who aged 19–78 years, were not currently pregnant and were without a prior diagnosis of cardiovascular disease or cancer.Outcome measuresGender-specific current smoking prevalence using the 1998–2017 Korea National Health and Nutrition Examination Survey.ResultsOur results showed gender-specific age and birth cohort effects. More specifically, the smoking prevalence peaked at their mid-20s (prevalence rate ratio (PRR): 1.54, 95% CI: 1.49 to 1.59) and cohort born in 1959–1963 (PRR: 1.63, 95% CI: 1.57 to 1.70) and then decreased in men. On the other hand, in women, the smoking prevalence consistently increased until their mid-40s (PRR: 1.53, 95% CI: 1.27 to 1.84) and in recent birth cohort groups (PRR in 1994–1998 cohort: 1.55, 95% CI: 1.13 to 2.13). The period effects declined from 1998−2002 to 2003–2007, following increasing fluctuations in both genders. The smoking-DPSEEA framework showed the absence of policy actions to target female smokers and emphasised a proactive approach that tackles the upstream causes for smoking in women.ConclusionsMen and women are clearly in different phases of the smoking epidemic in Korean population, and gender-tailored policies should be implemented.
Consolidation treatments after chemoradiotherapy in patients with locally advanced inoperable non-small cell lung cancer: a systematic review and network meta-analysis protocol
Authors: Zhao Ye , Feng Haiming , Tian Jinhui , Li Bin , Wang Cheng , Ge Long , Wang Jian kai , Yang Kehu , Yu Qin 
Published: April 2022

IntroductionConcurrent chemoradiotherapy (CCRT) is the standard of care for inoperable locally advanced non-small cell lung cancer. To further improve prognosis, the use of consolidation treatments after CCRT has been explored extensively. Although durvalumab is the only consolidation treatment recommended by national clinical practice guidelines, there have been many studies exploring the effectiveness of other agents. However, until now, no studies have compared all agents systematically, and no studies have provided evidence for the optimal combination of different CCRTs and consolidation treatments regimens. This systematic review will evaluate the comparative clinical efficacy of consolidation therapies after CCRT as well as various combinations of CCRTs and consolidation therapies.Methods and analysisPubMed, the Cochrane Controlled Register of Trials (CENTRAL), EMBASE and ClinicalTrials.gov will be searched for relevant information. The estimated end date for the search will be 3 February 2022. Each stage of the review, including the study section, data extraction and risk of bias and quality of evidence assessments, will be performed in duplicate. We will include randomised controlled trials that included participants who received CCRT and consolidation treatment in at least one treatment arm. The primary endpoints will be overall survival and progression-free survival. Tumour response, health-related quality of life, disease-free survival and treatment-related toxicity will be presented as secondary outcomes. Both traditional meta-analysis and network meta-analysis (NMA) with the Bayesian approach will be conducted. Subgroup analyses and meta-regression will be completed to investigate heterogeneity, and sensitivity analyses will be conducted to assess the robustness of the findings.Ethics and disseminationEthical approval and patient consent are not required as this study is a meta-analysis based on published studies. The results of this study will be submitted to a peer-reviewed journal for publication. In case of any changes in the protocol, protocol amendments will be updated in PROSPERO and explanations of these modifications will be described in the final report of this review. The results of this systematic review and NMA will be published in a peer-reviewed journal.PROSPERO registration numberCRD42021239433.
Relationship between age, workplace slips and the effectiveness of slip-resistant footwear among healthcare workers
Authors: Frost Gillian , Liddle Mark , Cockayne Sarah , Cunningham-Burley Rachel , Fairhurst Caroline , Torgerson David J 
Published: April 2022

ObjectivesTo explore any age-related trend in workplace slip rate and assess the effectiveness of appropriate slip-resistant footwear in preventing workplace slips by age.MethodsSecondary data analysis of the Stopping Slips among Healthcare Workers trial, a two-arm randomised controlled trial conducted between March 2017 and May 2019. 4553 National Health Service (NHS) staff across seven sites in England were randomised 1:1 to the intervention group (provision of 5* GRIP-rated slip-resistant footwear) or the control group (usual work footwear). The primary outcome was self-reported workplace slips, ascertained primarily through weekly text messages throughout the 14-week trial follow-up and analysed using mixed-effects negative binomial regression. This paper reports a control group-only analysis of the association between age and slip rate, and a full intention-to-treat analysis of the effectiveness of slip-resistant footwear by age.ResultsThe mean age of participants was 43 years (range 18–74). In the control group-only analysis, slip rate differed by age (p<0.001) with those aged 60+ having double the slip rate of those aged <30 years (95% CI 1.40 to 2.87). In the intention-to-treat analysis, the interaction between allocation and age was statistically significant (p=0.002). In addition, for all age groups except those aged <30 years, the slip rate in the intervention group was statistically significantly lower than the control group; the smallest incidence rate ratio (ie, the biggest effect) was 0.39 (95% CI 0.24 to 0.64) in the 60+ age group.ConclusionThe provision of appropriate slip-resistant footwear was more effective at reducing workplace slips for older NHS staff.
Long-read sequencing to resolve the parent of origin of a de novo pathogenicUBE3Avariant
Authors: Watson Christopher Mark , Jackson Lucy , Crinnion Laura A , Bonthron David T , Sheridan Eamonn 
Published: April 2022

BackgroundThe ever-increasing capacity of short-read sequencing instruments is driving the adoption of whole genome sequencing (WGS) as a universal approach to the diagnosis of rare genetic disorders. However, many challenging genomic regions remain, for which alternative technologies must be deployed in order to address the clinical question satisfactorily.MethodsHere we report the use of long-read sequencing to resolve ambiguity over a suspected diagnosis of Angelman syndrome.ResultsDespite a normal chromosomal microarray result and methylation studies at the imprinted 15q11q13 locus, the continued clinical suspicion of Angelman Syndrome prompted trio WGS of the proband and his parents. A de novo heterozygous frameshift variant, c.2370_2373del (NM_130838.2) p.(Asp790Glufs*7), inUBE3Awas identified. To determine the parental allele on which this variant arose, long-read sequencing of the flanking genomic region was performed. Comparison of the resulting haplotypes allowed us to determine that the pathogenic frameshift variant arose on the maternal allele, confirming a diagnosis of Angelman syndrome in this case.ConclusionLong-read nanopore sequencing provides significant clinical utility when assessing the parental origin of de novo variants.
Hyperglycemic control in acute ischemic stroke patients undergoing endovascular treatment: post hoc analysis of the Stroke Hyperglycemia Insulin Network Effort trial
Authors: Bains Navpreet K , Huang Wei , French Brandi R , Siddiq Farhan , Gomez Camilo R , Qureshi Adnan I 
Published: April 2022

BackgroundHyperglycemia has been associated with poor outcomes in acute ischemic stroke patients undergoing endovascular treatment. We analyzed the effect of intensive glucose control on death and disability rates in patients with acute ischemic stroke undergoing endovascular treatment.MethodsWe analyzed the effect of intensive (serum glucose <110 mg/dL) glucose treatment (compared with standard treatment, serum glucose <180 mg/dL) in patients who received endovascular treatment in the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial. We further analyzed the effect of area under the curve (AUC) of serum glucose, proportion of the time blood glucose was <140 mg/dL, and glucose variability defined as the glucose range during 72 hours. The primary outcomes were neurological deterioration within 72 hours and outcome at 90 days.ResultsA total of 146 patients (mean age 68.1±13.9 years, 50.7% men) underwent endovascular treatment for acute ischemic stroke; 72 and 74 patients were randomized to intensive and standard treatments, respectively. The rates of death (20.3% and 22.2%), favorable 90-day primary outcome (17.6% and 19.4%), and serious adverse events (41.9% and 56.98%) were similar between the two groups. The AUC of serum glucose was not associated with death within 90 days (OR 1, 95% CI 1 to 1) or favorable outcome at 90 days (OR 1, 95% CI 1 to 1). Glucose variability was not associated with death or favorable outcome at 90 days.ConclusionWe did not identify any beneficial effect of intensive glucose reduction on rates of death or favorable outcomes at 90 days among acute ischemic stroke patients undergoing endovascular treatment.
Reorienting of pramipexole as a promising therapy for acute pancreatitis in a rat model by suppressing TLR4\NF-κB p65\NLRP3 inflammasome signaling
Authors: Fawzy Hadeel A. , Mohammed Asmaa A. , Fawzy Hala M. , Fikry Ebtehal M. 
Published: April 2022

Acute pancreatitis (AP), a disorder of global importance, has a growing incidence and prevalence, particularly in the Western world. Its complications include pseudocysts and chronic pancreatitis. Pramipexole (PMX), a D2/3 receptor selecting agonist used in Parkinsonism, was reported to have anti-inflammatory effects. This study explored the potential curative role of PMX in an l-arginine-induced acute pancreatitis rat model in addition to a possible mechanistic pathway. Rats were divided randomly into three groups: control, l-arginine, and l-arginine + PMX. Seven days after AP induction, rats were decapitated and estimated for serum amylase, lipase, glucose, pancreatic inflammatory mediators toll-like receptor-4, nuclear factor κ B p65, serum tumor necrosis factor-α, NOD-, LRR and pyrin domain- containing protein 3 (NLRP3) inflammasome, caspase-1, interleukin 1β, oxidative biomarkers malondialdehyde, myeloperoxidase, nitrite/nitrate, reduced glutathione, and the apoptotic marker caspase-3, with pancreatic histopathological changes. l-arginine-mediated AP was proved by elevated serum lipase and amylase and pancreatic inflammatory, oxidative, and apoptotic markers with infiltration of inflammatory cells using hematoxylin and eosin stain. PMX improved all these adverse signs of AP greatly. PMX might be considered an innovative therapy for AP due to its remarkable antioxidant, antiapoptotic, and anti-inflammatory effects, which are attributed to the suppression of the NLRP3 inflammasome and its downstream inflammatory cytokines.
Based on proteomics to explore the mechanism of mecobalamin promoting the repair of injured peripheral nerves
Authors: Xiong Zong-liang , Wang Yao , Ma Xiang-Lin , Zhou Chong , Jiang Xiao-wen , Yu Wen-hui 
Published: April 2022

Mecobalamin is commonly used in the adjuvant intervention of various peripheral nerve injuries. Actin cytoskeleton plays a role in the regeneration of myelin and axon. Therefore, the purpose of this study was to explore the possibility of mecobalamin regulating actin cytoskeleton in repairing nerve injury. In this study, a crush injury on the right sciatic nerve of two groups of rats (12 in each group) was established. The control group was only given normal saline (i.g.), and the intervention group was given mecobalamin 1 mg/kg (i.g.). The rats were sacrificed on 28th day and the injured nerves were collected for proteomics. The result shows that regulation of actin cytoskeleton pathway changed significantly. The expression of protein Vav1 was verified by Western blot and immunofluorescence. In the intervention group, the nerve fiber structure was complete, the axons were dense and symmetrical, and the myelin sheath was compact and uniform in thickness. The positive rate of myelin basic protein and βⅢ-tubulin was higher than that in the control group. The findings of the study show that mecobalamin regulates the actin cytoskeleton in the repair of nerve damage and upregulates Vav1 in the regulation of actin cytoskeleton pathway.
Existence Solutions for a Class of Schrödinger-Maxwell Systems with Steep Well Potential
Authors: Yang Guocui , Duan Shengzhong 
Published: April 2022

In this paper, we are concerned with the system of the Schrödinger-Maxwell equations

−
Δ
u
+
λ
V

x

u
+
b
K

x

ϕ
u
=

u

p
−
2

u
,
in

R

3

,

−
Δ
ϕ
=
K

x

u

2

,
in

R

3

,

where

λ
,
b
>
0

are constants, and

3
<
p
<
6

. Under appropriate assumptions on

V

and

K

, we prove the existence of positive solutions in the case

3
<
p
<
4

via the truncation technique. Moreover, suppose that

V

may change sign, we also obtain the multiplicity of solutions for the case

4
<
p
<
6

.
Prognostic and Predictive Factors in Patients with Advanced HCC and Elevated Alpha-Fetoprotein Treated with Ramucirumab in Two Randomized Phase III Trials
Authors: Llovet Josep M. , Singal Amit G. , Villanueva Augusto , Finn Richard S. , Kudo Masatoshi , Galle Peter R. , Ikeda Masafumi , Callies Sophie , McGrath Louise M. , Wang Chunxiao , Abada Paolo , Widau Ryan C. , Gonzalez-Gugel Elena , Zhu Andrew X. 
Published: April 2022

Abstract

Purpose:
Ramucirumab is an effective treatment for patients with advanced hepatocellular carcinoma (aHCC) and baseline alpha-fetoprotein (AFP) ≥400 ng/mL. We aimed to identify prognostic and predictive factors of response to ramucirumab in patients with aHCC with AFP ≥400 ng/mL from the phase III REACH and REACH-2 randomized trials.

Patients and Methods:
Patients with aHCC, Child-Pugh class A with prior sorafenib treatment were randomized in REACH and REACH-2 (ramucirumab 8 mg/kg or placebo, biweekly). Meta-analysis of individual patient-level data (pooled population) from REACH (AFP ≥400 ng/mL) and REACH-2 was performed. A drug exposure analysis was conducted for those with evaluable pharmacokinetic data. To identify potential prognostic factors for overall survival (OS), multivariate analyses were performed using a Cox proportional hazards regression model. To define predictors of ramucirumab benefit, subgroup-by-treatment interaction terms were evaluated.

Results:
Of 542 patients (316 ramucirumab, 226 placebo) analyzed, eight variables had independent prognostic value associated with poor outcome (geographical region, Eastern Cooperative Oncology Group performance score ≥1, AFP &gt;1,000 ng/mL, Child-Pugh &gt;A5, extrahepatic spread, high neutrophil-to-lymphocyte ratio, high alkaline phosphatase and aspartate aminotransferase). Ramucirumab survival benefit was present across all subgroups, including patients with very aggressive HCC [above median AFP; HR: 0.64; 95% confidence interval (CI): 0.49–0.84] and nonviral aHCC (HR: 0.56; 95% CI: 0.40–0.79). While no baseline factor was predictive of a differential OS benefit with ramucirumab, analyses demonstrated an association between high drug exposure, treatment-emergent hypertension (grade ≥3), and increased ramucirumab benefit.

Conclusions:
Ramucirumab provided a survival benefit irrespective of baseline prognostic covariates, and this benefit was greatest in patients with high ramucirumab drug exposure and/or those with treatment-related hypertension.
Dual Fluorescence Isogenic Synthetic Lethal Kinase Screen and High-Content Secondary Screening for MUC16/CA125-Selective Agents
Authors: Rao Thapi D. , Xu Mengyao , Eng Stephanie , Yang Guangli , Manson Robin , Rosales Nestor , Kumar Raj , Veillard Irva E. , Zhou Qin , Iasonos Alexia , Ouerfelli Ouathek , Djaballah Hakim , Spriggs David R. , Yeku Oladapo O. 
Published: April 2022

Abstract
Significant strides have been made in the development of precision therapeutics for cancer. Aberrantly expressed glycoproteins represent a potential avenue for therapeutic development. The MUC16/CA125 glycoprotein serves as a biomarker of disease and a driver of malignant transformation in epithelial ovarian cancer. Previously, we demonstrated a proof-of-principle approach to selectively targeting MUC16+ cells. In this report, we performed a synthetic lethal kinase screen using a human kinome RNAi library and identified key pathways preferentially targetable in MUC16+ cells using isogenic dual-fluorescence ovarian cancer cell lines. Using a separate approach, we performed high-content small-molecule screening of six different libraries of 356,982 compounds for MUC16/CA125-selective agents and identified lead candidates that showed preferential cytotoxicity in MUC16+ cells. Compounds with differential activity were selected and tested in various other ovarian cell lines or isogenic pairs to identify lead compounds for structure–activity relationship (SAR) selection. Lead siRNA and small-molecule inhibitor candidates preferentially inhibited invasion of MUC16+ cells in vitro and in vivo, and we show that this is due to decreased activation of MAPK, and non–receptor tyrosine kinases. Taken together, we present a comprehensive screening approach to the development of a novel class of MUC16-selective targeted therapeutics and identify candidates suitable for further clinical development.
Tissue-Agnostic Activity of BRAF plus MEK Inhibitor in BRAF V600–Mutant Tumors
Authors: Adashek Jacob J. , Menta Arjun K. , Reddy Neha K. , Desai Aakash P. , Roszik Jason , Subbiah Vivek 
Published: April 2022

Abstract
BRAF plus MEK inhibitor combinations are currently FDA-approved for melanoma, non–small cell lung cancer, and anaplastic thyroid cancer. The lack of clinical benefit with BRAF inhibition in BRAF V600–mutated colorectal cancer has prevented its tissue-agnostic drug development. We reviewed the AACR GENIE database for the prevalence of BRAF V600 mutations across tumor types. We reviewed the literature for case reports of clinical responses, outcomes in patients with BRAF V600 mutation—positive nonmelanoma malignancies who received BRAF inhibitor therapy, and data from published adult and pediatric trials. BRAF V600 mutations are prevalent across multiple nonmelanoma malignancies (&gt;40 different tumor types), lead to oncogene addiction, and are clinically actionable in a broad range of adult and pediatric nonmelanoma rare malignancies. Continued tissue-agnostic drug development is warranted beyond the current BRAF plus MEK approved cancers.