bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caregiving experiences of informal caregivers of adult stroke patients during the COVID-19 pandemic: a qualitative systematic review protocol
Authors: Schaefer Ashley B. , Palokas Michelle 
Published: January 2023

Objective:
The objective of this review is to identify, appraise, and synthesize the best available qualitative evidence on the caregiving experiences of informal caregivers of adult stroke patients during the COVID-19 pandemic.

Introduction:
The functional and health outcomes of stroke patients are directly impacted by the mental and physical well-being of the patient’s informal caregiver, which have been negatively affected by COVID-19 due to a lack of caregiver education and competency in caring for stroke patients. Therefore, improvement of the informal caregiver experience will preserve the stroke survivor–caregiver relationship and the care goals of stroke patients.

Inclusion criteria:
This review will consider qualitative studies focusing on the experiences of informal caregivers of adult stroke patients during COVID-19. Only informal caregivers will be included, defined as individuals of any age, gender, or culture who provide care, typically unpaid, to someone with whom they have a personal relationship (ie, family or friend). Studies conducted in inpatient settings, rehabilitation settings, community care settings, or home care settings will be considered.

Methods:
The databases to be searched include MEDLINE, CINAHL, Embase, Web of Science, and PsycINFO. Sources of unpublished studies and gray literature will include ProQuest Dissertations and Theses, MedNar, and the American Heart Association. Studies published from 2019 to the present will be considered and data synthesis will be conducted using the meta-aggregation approach. Confidence in the findings will be assessed using the ConQual approach.

Systematic review registration number:
PROSPERO CRD42022326666
A Method of Evaluating the Driving Force and Stresses During Tube Die Expansion
Authors: Zhao Zijian , Bouzid Abdel-Hakim , Zhu Linbo 
Published: January 2023

AbstractIn this study, an analytical approach based on the energy method is used to estimate the force required to expand tubes with different die shapes. The proposed method calculates the driving force using the energy of deformation and the energy produced by friction. The new approach greatly reduces the difficulty of the analysis and simplifies the calculation. The stress distribution in the transition zone is also estimated using an analytical approach based on a self-adaption of the stress–strain curve. The approach is validated using four different numerical axisymmetric finite element models with different sizes, materials, and die shapes subjected to push and pull die expansion. Additionally, stainless steel and copper 3/8 in. tubes have been expanded with a prolate spheroid (oval) die in an experimental test bench under the two conditions of push and pull. The tangential and longitudinal strains and driving forces are monitored and recorded during the expansion process. Finally, the results from the three approaches show a very good agreement.
TXNIPDNA methylation is associated with glycemic control over 28 years in type 1 diabetes: findings from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study
Authors: Miller Rachel G , Mychaleckyj Josyf C , Onengut-Gumuscu Suna , Orchard Trevor J , Costacou Tina 
Published: January 2023

IntroductionDNA methylation (DNAme) has been cross-sectionally associated with type 2 diabetes and hemoglobin A1c (HbA1c) in the general population. However, longitudinal data and data in type 1 diabetes are currently very limited. Thus, we performed an epigenome-wide association study (EWAS) in an observational type 1 diabetes cohort to identify loci with DNAme associated with concurrent and future HbA1cs, as well as other clinical risk factors, over 28 years.Research design and methodsWhole blood DNAme in 683 597 CpGs was analyzed in the Pittsburgh Epidemiology of Diabetes Complications study of childhood onset (<17 years) type 1 diabetes (n=411). An EWAS of DNAme beta values and concurrent HbA1c was performed using linear models adjusted for diabetes duration, sex, pack years of smoking, estimated cell type composition variables, and technical/batch covariates. A longitudinal EWAS of subsequent repeated HbA1c measures was performed using mixed models. We further identified methylation quantitative trait loci (meQTLs) for significant CpGs and conducted a Mendelian randomization.ResultsDNAme at cg19693031 (Chr 1,Thioredoxin-Interacting Protein(TXNIP)) and cg21534330 (Chr 17,Casein Kinase 1 Isoform Delta) was significantly inversely associated with concurrent HbA1c. In longitudinal analyses, hypomethylation of cg19693031 was associated with consistently higher HbA1c over 28 years, and with higher triglycerides, pulse rate, and albumin:creatinine ratio (ACR) independently of HbA1c. We further identified 34 meQTLs inSLC2A1/SLC2A1-AS1significantly associated with cg19693031 DNAme.ConclusionsOur results extend prior findings thatTXNIPhypomethylation relates to worse glycemic control in type 1 diabetes by demonstrating the association persists over the long term. Additionally, the associations with triglycerides, pulse rate, and ACR suggestTXNIPDNAme could play a role in vascular damage independent of HbA1c. These findings strengthen potential for interventions targeting TXNIP to improve glycemic control in type 1 diabetes through its role inSLC2A1/glucose transporter 1-mediated glucose regulation.
Effect of polyphenol compounds onHelicobacter pylorieradication: a systematic review with meta-analysis
Authors: Wang Qiuxiang , Yao Chengjiao , Li Yilin , Luo Lihong , Xie Fengjiao , Xiong Qin , Feng Peimin 
Published: January 2023

ObjectivesPolyphenol compounds are classified as organic compounds with phenolic units exhibiting a variety of biological functions. This meta-analysis aims to assess the efficacy and safety of polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) in eradicatingHelicobacter pylori.DesignSystematic review and meta-analysis.MethodsLiterature searches were conducted on PubMed, Embase, The Cochrane Library, Web of Science, Medline, Chinese National Knowledge Infrastructure database, Chinese Scientific Journal Database and Wan Fang database from inception to January 2022. All randomised controlled trials comparing polyphenol compounds with the placebo or used as an adjunct treatment are included in this meta-analysis.The treatment effect for dichotomous outcomes was assessed using risk ratio (RR), while for continuous outcomes, mean differences both with 95% CIs, were used. Subgroup analyses were carried out for different treatment schemes and polyphenol compound species.Results12 trials were included in the meta-analysis. The total eradication rate ofH.pyloriin the polyphenol compounds group was higher than in the group without polyphenol compounds. Statistical significance was also observed (RR 1.19, 95% CI 1.03 to 1.38, p=0.02). The most frequent adverse effects of polyphenol compounds included diarrhoea, headache and vomiting. However, there were no differences regarding side effects between the two groups (RR 1.47, 95% CI 0.83 to 2.58, p=0.18). In subgroup analyses, theH.pylorieradication rate regimens with polyphenols therapy was superior to that of regimens without polyphenols therapy in the polyphenols versus placebo subgroup (RR 4.23, 95% CI 1.38 to 12.95, p=0.01), polyphenols plus triple therapy versus triple therapy subgroup (RR 1.11, 95% CI 1.01 to 1.22, p=0.03).ConclusionPolyphenol compounds can improveH.pylorieradication rates. Polyphenol compounds plus standard triple therapy can significantly improve the eradication. However, no evidence of a higher incidence of side effects could be found.PROSPERO registration numberCRD42022307477.
Face masks while exercising trial (MERIT): a cross-over randomised controlled study
Authors: Jones Nicholas , Oke Jason , Marsh Seren , Nikbin Kurosh , Bowley Jonathan , Dijkstra H Paul , Hobbs FD Richard , Greenhalgh Trisha 
Published: January 2023

ObjectivesPhysical exertion is a high-risk activity for aerosol emission of respiratory pathogens. We aimed to determine the safety and tolerability of healthy young adults wearing different types of face mask during moderate-to-high intensity exercise.DesignCross-over randomised controlled study, completed between June 2021 and January 2022.ParticipantsVolunteers aged 18–35 years, who exercised regularly and had no significant pre-existing health conditions.InterventionsComparison of wearing a surgical, cloth and filtering face piece (FFP3) mask to no mask during 4×15 min bouts of exercise. Exercise was running outdoors or indoor rowing at moderate-to-high intensity, with consistency of distance travelled between bouts confirmed using a smartphone application (Strava). Each participant completed each bout in random order.OutcomesThe primary outcome was change in oxygen saturations. Secondary outcomes were change in heart rate, perceived impact of face mask wearing during exercise and willingness to wear a face mask for future exercise.ResultsAll 72 volunteers (mean age 23.9) completed the study. Changes in oxygen saturations did not exceed the prespecified non-inferiority margin (2% difference) with any mask type compared with no mask. At the end of exercise, the estimated average difference in oxygen saturations for cloth mask was −0.07% (95% CI −0.39% to 0.25%), for surgical 0.28% (−0.04% to 0.60%) and for FFP3 −0.21% (−0.53% to 0.11%). The corresponding estimated average difference in heart rate for cloth mask was −1.20 bpm (95% CI −4.56 to 2.15), for surgical 0.36 bpm (95% CI −3.01 to 3.73) and for FFP3 0.52 bpm (95% CI −2.85 to 3.89). Wearing a face mask caused additional symptoms such as breathlessness (n=13, 18%) and dizziness (n=7, 10%). 33 participants broadly supported face mask wearing during exercise, particularly indoors, but 22 were opposed.ConclusionThis study adds to previous findings (mostly from non-randomised studies) that exercising at moderate-to-high intensity wearing a face mask appears to be safe in healthy, young adults.Trial registration numberNCT04932226
Explaining the negative effects of patient participation in patient safety: an exploratory qualitative study in an academic tertiary healthcare centre in the Netherlands
Authors: Van der Voorden Michael , Ahaus Kees , Franx Arie 
Published: January 2023

ObjectiveAlthough previous studies largely emphasize the positive effects of patient participation in patient safety, negative effects have also been observed. This study focuses on bringing together the separate negative effects that have been previously reported in the literature. This study set out to uncover how these negative effects manifest themselves in practice within an obstetrics department.DesignAn exploratory qualitative interview study with 16 in-depth semistructured interviews. The information contained in the interviews was deductively analysed.SettingThe study was conducted in one tertiary academic healthcare centre in the Netherlands.ParticipantsPatients (N=8) and professionals (N=8) from an obstetrics department.ResultsThe results of this study indicate that patient participation in patient safety comes in five different forms. Linked to these different forms, four negative effects of patient participation in patient safety were identified. These can be summarised as follows: patients’ confidence decreases, the patient–professional relationship can be negatively affected, more responsibility can be demanded of the patient than they wish to accept and the professional has to spend additional time on a patient.ConclusionThis study identifies and brings together four negative effects of patient participation in patient safety that have previously been individually identified elsewhere. In our interviews, there was a consensus among patients and professionals on five different forms of participation that would allow patients to positively participate in patient safety. Further studies should investigate ways to prevent and to mitigate the potential negative effects of patient participation.
Efficacy of pericapsular nerve group (PENG) block on perioperative pain management in elderly patients undergoing hip surgical procedures: a protocol for a systematic review with meta-analysis and trial sequential analysis
Authors: Zheng Jianqiao , Du Li , Chen Guo , Zhang Lu , Deng Xiaoqian , Zhang Weiyi 
Published: January 2023

IntroductionAn increasing number of elderly patients suffer from hip diseases associated with moderate to severe perioperative pain during the accelerating global ageing process. Optimal analgesia can decrease perioperative complications and facilitate elderly patients’ perioperative recovery. Pericapsular nerve group (PENG) block is a relatively new, analgesia adequate and motor-sparing block technique for perioperative pain management of hip diseases. However, the efficacy of PENG block remains unclear as the limited clinical evidence. Then, we will perform a protocol for a systematic review and meta-analysis to identify the efficacy of PENG block for perioperative pain management.Methods and analysisPubMed, Ovid Medline, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Chinese BioMedical Literature, Wanfang and VIP databases will be searched from inception to August 2022 to identify randomised controlled trials of elderly patients accepting PENG block for hip diseases. The primary outcome will be the pain intensity after pain management. Secondary outcomes will be quadriceps strength, perioperative rescue analgesia information and perioperative complications. Assessment of heterogeneity will be primarily inspected by forest plots. If there is no indication of funnel plot asymmetry, a random-effects meta-analysis will be performed. The Cochrane risk-of-bias tool, Grading of Recommendations Assessment, Development and Evaluation and trial sequential analysis will be conducted to evaluate the evidence quality and control the random errors. Funnel plots and Egger’s regression test will be performed to evaluate publication bias.Ethics and disseminationEthical approval was not required for this systematic review protocol. The results will be disseminated through peer-reviewed publications.PROSPERO registration numberCRD42022313895
Nab-PIPAC: a phase IB study protocol of intraperitoneal cisplatin and nab-paclitaxel administered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in the treatment of advanced malignancies confined to the peritoneal cavity
Authors: Lang Noemie , Diciola Antonella , Labidi-Galy Intidhar , Ris Frédéric , Di Marco Mariagrazia , Mach Nicolas , Petignat Patrick , Toso Christian , Undurraga Manuela , Hubner Martin 
Published: January 2023

IntroductionIntraperitoneal dissemination is a major problem resulting in very poor prognosis and a rapid marked deterioration in the quality of life of patients. Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is an emergent laparoscopic procedure aiming to maximise local efficacy and to reduce systemic side effects.Methods and analysisNab-PIPAC, a bicentre open-label phase IB, aims to evaluate safety of nab-paclitaxel and cisplatin association using in patients with peritoneal carcinomatosis (PC) of gastric, pancreatic or ovarian origin as ≥1 prior line of systemic therapy. Using a 3+3 design, sequential intraperitoneal laparoscopic application of nab-paclitaxel (7.5, 15, 25, 37.5, 52.5 and 70 mg/m2) and cisplatin (10.5 mg/m2) through a nebuliser to a high-pressure injector at ambient temperature with a maximal upstream pressure of 300 psi. Treatment maintained for 30 min at a pressure of 12 mm Hg and repeated4–6 weeks intervals for three courses total.A total of 6–36 patients are expected, accrual is ongoing. Results are expected in 2024.The primary objective of Nab-PIPAC trial is to assess tolerability and safety of nab-paclitaxel and cisplatin combination administered intraperitoneally by PIPAC in patients with PC of gastric, pancreatic or ovarian origin. This study will determine maximum tolerated dose and provide pharmacokinetic data.Ethic and disseminationEthical approval was obtained from the ethical committees of Geneva and Vaud (CCER-2018-01327). The study findings will be published in an open-access, peer-reviewed journal and presented at relevant conferences and research meetings.Trial registration numberNCT04000906.
Prevalence of secondary insults and outcomes of patients with traumatic brain injury intubated in the prehospital setting: a retrospective cohort study
Authors: Butterfield Michael , Bodnar Daniel , Williamson Frances , Parker Lachlan , Ryan Glenn 
Published: January 2023

BackgroundPrehospital neuroprotective strategies aim to prevent secondary insults (SIs) in traumatic brain injury (TBI). This includes haemodynamic optimisation in addition to oxygenation and ventilation targets achieved through rapid sequence intubation (RSI).The primary aim was to report the incidence and prevalence of SIs (prolonged hypotension, prolonged hypoxia and hyperventilation) and outcomes of patients with TBI who were intubated in the prehospital setting.MethodsA retrospective cohort study of adult patients with TBI who underwent RSI by a metropolitan road-based service in South-East Queensland, Australia between 1 January 2017 and 31 December 2020. Patients were divided into two cohorts based on the presence or absence of any SI sustained. Prolonged SIs were defined as occurring for ≥5 min. The association between SIs and mortality was examined in multivariable logistic regression and reported with adjusted ORs (aORs) and 95% CIs.Results277 patients were included for analysis. Median ‘Head’ Abbreviated Injury Scale and Injury Severity Score were 4 (IQR: 3–5) and 26 (IQR: 17–34), respectively. Most episodes of prolonged hypotension and prolonged hypoxia were detected with the first patient contact on scene. Overall, 28-day mortality was 26%. Patients who sustained any SI had a higher mortality than those sustaining no SI (34.9% vs 14.7%, p<0.001). Prolonged hypoxia was an independent predictor of mortality (aOR 4.86 (95% CI 1.65 to 15.61)) but not prolonged hypotension (aOR 1.45 (95% CI 0.5 to 4.25)) or an end-tidal carbon dioxide <30 mm Hg on hospital arrival (aOR 1.28 (95% CI 0.5 to 3.21)).ConclusionSIs were common in the early phase of prehospital care. The association of prolonged hypoxia and mortality in TBI is potentially more significant than previously recognised, and if corrected early, may improve outcomes. There may be a greater role for bystander intervention in prevention of early hypoxic insult in TBI.
Gut commensalParabacteroides distasonisalleviates inflammatory arthritis
Authors: Sun Haijian , Guo Yunke , Wang Haidan , Yin Ailing , Hu Jing , Yuan Tianjie , Zhou Shuxin , Xu Weichen , Wei Peng , Yin Shusheng , Liu Panru , Guo Xi , Tang Yizhao , Yan Yujiao , Luo Zichen , Wang Majie , Liang Qingqing , Wu Peng , Zhang Aifeng , Zhou Zhuxiu , Chen Yueyue , Li Yongming , Li Jing , Shan Jinjun , Zhou Wei 
Published: January 2023

ObjectiveGut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate the development of RA.DesignMicrobiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing and shotgun metagenomics. Collagen-induced arthritic mice and TNF-α transgenic mice were used to evaluate the roles of the gut commensalParabacteroides distasonisin RA. The effects ofP. distasonis-derived microbial metabolites on the differentiation of CD4+T cells and macrophage polarisation were also investigated.ResultsThe relative abundance ofP. distasonisin new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28). Oral treatment of arthritic mice with liveP. distasonis(LPD) considerably ameliorated RA pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic acid (DCA), isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages. A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids. The natural product ginsenoside Rg2 exhibited its anti-RA effects by promoting the growth ofP. distasonis.ConclusionsP. distasonisand ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.
Clinical and genetic features of GATOR1 complex-associated epilepsy
Authors: Yin Kaili , Lei Xingxing , Yan Zhaofen , Yang Yujiao , Deng Qinqin , Lu Qiang , Zhang Xue , Wang Mengyang , Liu Qing 
Published: January 2023

ObjectivesTo analyse the prevalence of pathogenic variants inDEPDC5,NPRL2andNPRL3that encode the GATOR1 (GTPase-activating protein towards the Rags 1) complex, a modulator in the mammalian target of rapamycin (mTOR) pathway, and to define the characteristics of GATOR1-associated epilepsy.MethodsClinical details and whole-exome sequencing data of 170 novel probands with lesional or non-lesional epilepsy were retrieved. Candidate variants in GATOR1 genes were verified by Sanger sequencing, and cosegregate analysis was performed. The pathogenicity of variants and their effect on mTOR signalling were investigated.ResultsTwo novel frameshift variants and one recurrent nonsense variant were detected inDEPDC5, with a prevalence of 1.8% (3 out of 170) in the whole cohort and 3.1% (3 out of 97) in focal epilepsies. These variants cosegregated in pedigrees with epilepsy, respectively. Rare missense variants inNPRL2andNPRL3did not segregate with epilepsy in families, respectively. Epileptic phenotypes of 21 patients withDEPDC5variants showed focal seizures with non-lesional variable foci that were predominantly sleep-related, with a median onset age of 10 years (range 1–30). Seizure outcome was variable. About 24% of patients were drug-resistant, and seizure attacks were absent in 33% of variant carriers. Of 13 patients who experienced seizures, 54% tended to resolve spontaneously. Functional assessments showed that the three variants affectedDEPDC5expression. These loss-of-function (LoF) variants affected theDEPDC5-dependent inhibition of mTOR.ConclusionsPatients carryingDEPDC5-LoF variants might show a high prevalence of focal seizures with a dynamic phenotype, indicating reduced penetrance and self-resolving features. The associated epilepsy was caused by loss of inhibition of the mTOR pathway. The pathogenicity of missense variants in GATOR1 genes should be cautiously evaluated.
Ordovician tephra distribution, tephrochronology and geochronology
Authors: McLaughlin Patrick I. , Normore Leon , Sell Bryan K. , Ramezani Jahandar 
Published: January 2023

Abstract
The study of Ordovician tephras yields a wealth of valuable information about regional tectonism, sedimentation, stratigraphic correlation, and process rates. As such, these layers are prized by geologists and are the subject of a rich literature. Ordovician tephra studies were pioneering, particularly in the development of chemical fingerprinting to improve precision in tephrochronology. Modern radioisotope geochronology utilizes zircons and other phenocrysts from these layers to generate eruption ages with uncertainty on the order of a hundred thousand years. When integrated with biostratigraphy, chemostratigraphy and astrochronology, tephra ages provide an unparalleled opportunity to constrain process rates. Fifty such Ordovician tephra ages have been published over the last decade from U–Pb analysis of individual zircon phenocrysts, providing geochronological coverage across all stages of the Ordovician. Laurentia dominates this coverage (24) followed by the Baltic Basin (12), North Gondwana (11), Cuyania (four) and the Siberian Tungus Basin (one). Future tephra studies should seek to fill the numerous remaining gaps in the Ordovician time scale.