bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain changes in neuroimaging of adult patients with vitamin D deficiency: systematic review protocol
Authors: Porto Catarina Magalhães , Leão Rita de Cássia Hoffmann , Sousa Renata Alves de , Diniz Paula Rejane Beserra , Silva Tatiana de Paula Santana da , Sougey Everton Botelho 
Published: February 2023

IntroductionBrain abnormalities detected through neuroimaging are described in patients with vitamin D deficiency, however, it is still not clear which cerebral alterations are more frequent and characteristic in this population. Thus, this review aims to identify and classify which are the main and most frequent brain changes found by neuroimaging in patients with vitamin D deficiency.Methods and analysisThe study protocol was constructed in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and the leading research question was formulated through Population, Intervention, Comparator, Outcome, Setting. The evidence will be researched at the following electronic databases: PubMed, PsycINFO, Scopus, Web of Science and EMBASE. Two researchers will work in the selection, analysis and inclusion phases of the articles. In the case of divergence, a third-party reviewer will be contacted. The following studies will be included: (1) cohort studies, case–control studies and cross-sectional studies; (2) studies carried out on patients with serum 25-hydroxyvitamin D levels below 30 ng/mL; (3) studies conducted with an adult population; (4) studies using neuroimaging methods. Articles considered eligible will be analysed by the Newcastle-Ottawa Quality Assessment Scale/cross-section studies to evaluate study quality. The survey will be conducted from June to December 2022.Ethics and disseminationThe identification of the main and most frequent brain alterations found through neuroimaging in patients with vitamin D deficiency can guide professionals as to the identification which of the main cerebral pathologies detected through neuroimaging are related to vitamin D deficiency, in choosing more sensitive and specific neuroimaging tests to detect these brain changes, in addition to emphasising the importance of monitoring and maintaining adequate serum levels of vitamin D, in order to reduce possible cognitive sequelae. Results will be announced at national and international conferences.PROSPERO registration numberCRD42018100074.
Protocol for the INFORMED (Individualised Patient Care and Treatment for Maternal Diabetes) Study: a randomised controlled trial embedded within routine care
Authors: Dingena Cassy F , Mahendra Anvesha , Holmes Melvin J , Clement Naomi S , Scott Eleanor M , Zulyniak Michael A 
Published: February 2023

IntroductionDiabetes in pregnancy presents a unique physiological challenge to manage glycaemia while maintaining adequate nourishment for the growing fetus. Women with diabetes who become pregnant are at greater risk of adverse maternal and newborn outcomes, compared with women without diabetes. Evidence suggests that control of (postprandial) glycaemia is key to manage maternal and offspring health but it is not yet clear (1) how diet and lifestyle moderate these shifts across the full duration of pregnancy or (2) what aspects of maternal and offspring health are associated with dysglycaemia.Methods and analysisTo investigate these gaps, a cross-over randomised clinical trial has been embedded within routine clinical care. Seventy-six pregnant women in their first trimester with type 1 or type 2 diabetes (with or without medication) attending their routine antenatal appointments at National Health Service (NHS) Leeds Teaching Hospitals will be recruited. Following informed consent, data on women’s health, glycaemia, pregnancy and delivery will be shared by the NHS with researchers. At each visit in the first (10–12 weeks), second (18–20 weeks) and third (28–34 weeks) trimester, participants will be asked for consent to: (1) lifestyle and diet questionnaires, (2) blood for research purposes and (3) analysis of urine collected at clinical visits. Additionally, participants will be asked to consume two blinded meals in duplicate in second and third trimester. Glycaemia will be assessed by continuous glucose monitoring as part of routine care. The primary outcome is the effect of experimental meals (high vs low protein) on postprandial glycaemia. Secondary outcomes include (1) the association between dysglycaemia and maternal and newborn health, and (2) the association between maternal metabolic profiles in early pregnancy with dysglycaemia in later pregnancy.Ethics and disseminationThe Leeds East Research Ethics Committee and NHS (REC: 21/NE/0196) approved the study. Results will be published in peer-reviewed journals and disseminated to participants and the wider public.Trial registration numberISRCTN57579163.
School readiness of children at high risk of cerebral palsy randomised to early neuroprotection and neurorehabilitation: protocol for a follow-up study of participants from four randomised clinical trials
Authors: Boyd Roslyn N , Novak Iona , Morgan Catherine , Bora Samudragupta , Sakzewski Leanne , Ware Robert S , Comans Tracy , Fahey Michael Collingwood , Whittingham Koa , Trost Stewart , Pannek Kerstin , Pagnozzi Alex , Mcintyre Sarah , Badawi Nadia , Smithers Sheedy Hayley , Palmer Kirsten Rebecca , Burgess Andrea , Keramat Syed Afroz , Bell Kristie , Hines Ashleigh , Benfer Katherine , Wotherspoon Jane , Gascoigne-Pees Laura , Leishman Shaneen , Oftedal Stina 
Published: February 2023

IntroductionSchool readiness includes cognitive, socio-emotional, language and physical growth and development domains which share strong associations with life-course opportunities. Children with cerebral palsy (CP) are at increased risk of poor school readiness compared with their typically developing peers. Recently, earlier diagnosis of CP has allowed interventions to commence sooner, harnessing neuroplasticity. First, we hypothesise that early referral to intervention for children at-risk of CP will lead to improved school readiness at 4–6 years relative to placebo or care as usual. Second, we hypothesise that receipt of early diagnosis and early intervention will lead to cost-savings in the form of reduced healthcare utilisation.Methods and analysisInfants identified as at-risk of CP ≤6 months corrected age (n=425) recruited to four randomised trials of neuroprotectants (n=1), early neurorehabilitation (n=2) or early parenting support (n=1) will be re-recruited to one overarching follow-up study at age 4–6 years 3 months. A comprehensive battery of standardised assessments and questionnaires will be administered to assess all domains of school readiness and associated risk factors. Participants will be compared with a historical control group of children (n=245) who were diagnosed with CP in their second year of life. Mixed-effects regression models will be used to compare school readiness outcomes between those referred for early intervention versus placebo/care-as-usual. We will also compare health-resource use associated with early diagnosis and intervention versus later diagnosis and intervention.Ethics and disseminationThe Children’s Health Queensland Hospital and Health Service, The University of Queensland, University of Sydney, Monash University and Curtin University Human Research Ethics Committees have approved this study. Informed consent will be sought from the parent or legal guardian of every child invited to participate. Results will be disseminated in peer-reviewed journals, scientific conferences and professional organisations, and to people with lived experience of CP and their families.Trial registration numberACTRN12621001253897.
Derivation and validation of clinical prediction rules for diagnosis of infectious mononucleosis: a prospective cohort study
Authors: de Paor Muireann , Boland Fiona , Cai Xinyan , Smith Susan , Ebell Mark H , Mac Donncha Eoin , Fahey Tom 
Published: February 2023

ObjectivesInfectious mononucleosis (IM) is a clinical syndrome that is characterised by lymphadenopathy, fever and sore throat. Although generally not considered a serious illness, IM can lead to significant loss of time from school or work due to profound fatigue, or the development of chronic illness. This study aimed to derive and externally validate clinical prediction rules (CPRs) for IM caused by Epstein-Barr virus (EBV).DesignProspective cohort study.Setting and participants328 participants were recruited prospectively for the derivation cohort, from seven university-affiliated student health centres in Ireland. Participants were young adults (17–39 years old, mean age 20.6 years) with sore throat and one other additional symptom suggestive of IM. The validation cohort was a retrospective cohort of 1498 participants from a student health centre at the University of Georgia, USA.Main outcome measuresRegression analyses were used to develop four CPR models, internally validated in the derivation cohort. External validation was carried out in the geographically separate validation cohort.ResultsIn the derivation cohort, there were 328 participants, of whom 42 (12.8%) had a positive EBV serology test result. Of 1498 participants in the validation cohort, 243 (16.2%) had positive heterophile antibody tests for IM. Four alternative CPR models were developed and compared. There was moderate discrimination and good calibration for all models. The sparsest CPR included presence of enlarged/tender posterior cervical lymph nodes and presence of exudate on the pharynx. This model had moderate discrimination (area under the receiver operating characteristic curve (AUC): 0.70; 95% CI: 0.62–0.79) and good calibration. On external validation, this model demonstrated reasonable discrimination (AUC: 0.69; 95% CI: 0.67–0.72) and good calibration.ConclusionsThe alternative CPRs proposed can provide quantitative probability estimates of IM. Used in conjunction with serological testing for atypical lymphocytosis and immunoglobulin testing for viral capsid antigen, CPRs can enhance diagnostic decision-making for IM in community settings.
Piloting of a minimum data set for older people living in care homes in England: protocol for a longitudinal, mixed-methods study
Authors: Towers Ann-Marie , Gordon Adam , Wolters Arne Timon , Allan Stephen , Rand Stacey , Webster Lucy Anne , Crellin Elizabeth , Brine Richard James , De Corte Kaat , Akdur Gizdem , Irvine Lisa , Burton Jennifer , Hanratty Barbara , Killett Anne , Meyer Julienne , Jones Liz , Goodman Claire 
Published: February 2023

IntroductionHealth and care data are routinely collected about care home residents in England, yet there is no way to collate these data to inform benchmarking and improvement. The Developing research resources And minimum data set for Care Homes’ Adoption and use study has developed a prototype minimum data set (MDS) for piloting.Methods and analysisA mixed-methods longitudinal pilot study will be conducted in 60 care homes (approximately 960 residents) in 3 regions of England, using resident data from cloud-based digital care home records at two-time points. These will be linked to resident and care home level data held within routine National Health Service and social care data sets. Two rounds of focus groups with care home staff (n=8–10 per region) and additional interviews with external stakeholders (n=3 per region) will explore implementation and the perceived utility of the MDS. Data will be assessed for completeness and timeliness of completion. Descriptive statistics, including percentage floor and ceiling effects, will establish data quality. For validated scales, construct validity will be assessed by hypothesis testing and exploratory factor analysis will establish structural validity. Internal consistency will be established using Cronbach’s alpha. Longitudinal analysis of the pilot data will demonstrate the value of the MDS to each region. Qualitative data will be analysed inductively using thematic analysis to understand the complexities of implementing an MDS in care homes for older people.Ethics and disseminationThe study has received ethical approval from the London Queen’s Square Research Ethics Committee (22/LO/0250). Informed consent is required for participation. Findings will be disseminated to: academics working on data use and integration in social care, care sector organisations, policy makers and commissioners. Findings will be published in peer-reviewed journals. Partner NIHR Applied Research Collaborations, the National Care Forum and the British Geriatrics Society will disseminate policy briefs.
National survey of Australian cardiac rehabilitation programmes: does current exercise programming adhere to evidence-based guidelines and best practice?
Authors: Hollings Matthew , Mavros Yorgi , Freeston Jonathan , Fiatarone Singh Maria 
Published: February 2023

ObjectivesThe efficacy of exercise-based cardiac rehabilitation (CR) for patient outcomes is well established, with better outcomes when delivery meets recommended guidelines. The aim of this study was to assess how well Australian practice aligns with national CR guidelines for exercise assessment and prescription.MethodThis cross-sectional online survey was distributed to all 475 publicly listed CR services in Australia and consisted of four sections: (1) Programme and client demographics, (2) aerobic exercise characteristics, (3) resistance exercise characteristics and (4) pre-exercise assessment, exercise testing and progression.ResultsIn total, 228 (54%) survey responses were received. Only three of five Australian guideline recommendations were consistently reported to be followed in current CR programmes: assessment of physical function prior to exercise (91%), prescription of light-moderate exercise intensity (76%) and review of referring physician results (75%). Remaining guidelines were commonly not implemented. For example, only 58% of services reported an initial assessment of resting ECG/heart rate, and only 58% reported the concurrent prescription of both aerobic and resistance exercise, which may have been influenced by equipment availability (p<0.05). Exercise-specific assessments such as muscular strength (18%) and aerobic fitness (13%) were uncommonly reported, although both were more frequent in metropolitan services (p<0.05) or when an exercise physiologist was present (p<0.05).ConclusionsClinically relevant deficits in national CR guideline implementation are common, potentially influenced by location, exercise supervisor and equipment availability. Key deficiencies include the lack of concurrent aerobic and resistance exercise prescription and infrequent assessment of important physiological outcomes including resting heart rate, muscular strength and aerobic fitness.
Lifestyle physical activity and rapid-rate non-sustained ventricular tachycardia in arrhythmogenic cardiomyopathy
Authors: Ramos-Maqueda Javier , Migueles Jairo H , Molina-Jiménez María , Ruiz-González David , Cabrera-Borrego Eva , Ruiz Salas Amalio , Soriano-Maldonado Alberto , Jimenez-Jaimez Juan 
Published: February 2023

ObjectiveTo investigate the association of accelerometer-measured lifestyle physical activity with rapid-rate non-sustained ventricular tachycardias (RR-NSVTs) in patients with arrhythmogenic cardiomyopathy (AC).MethodsThis multicentre, observational study enrolled 72 patients with AC, including right, left and biventricular forms of the disease, with underlying desmosomal and non-desmosomal mutations. Lifestyle physical activity, objectively monitored with accelerometers (ie, movement sensors) and RR-NSVT, identified as >188 bpm and >18 beats from a textile Holter ECG for 30 days.ResultsSixty-three patients with AC (38±17.6 years, 57% men) were included. A total of 17 patients experienced ≥1 RR-NSVTs, and a total of 35 events were recorded. The odds of occurrence of ≥1 RR-NSVT during the recording did not increase as a function of either total physical activity (OR 0.95, 95% CI (CI95%) 0.68 to 1.30 for 60 min increase) or moderate-to-vigorous activities (OR 0.89, CI95%0.71 to 1.08 for 5 min increase). Participants presenting RR-NSVTs during the recording (n=17) did not present greater odds of RR-NSVT in the days with more time either in total physical activity (OR 1.05, CI95%0.84 to 1.29 for additional 60 min) or moderate-to-vigorous activities (OR 1.05, CI95%0.97 to 1.12 for additional 5 min). Physical activity levels were neither different between the patients with and without RR-NSVTs during the recording period nor in the days of occurrence of RR-NSVT compared with the rest of the days. Finally, 4 of the 35 RR-NSVTs recorded in the 30 days occurred during physical activity (3 during moderate-to-vigorous intensity and 1 during light-intensity activities).ConclusionsThese findings suggest that lifestyle physical activity is not associated with RR-NSVTs in patients with AC.
Downregulation of phosphoserine phosphatase potentiates tumor immune environments to enhance immune checkpoint blockade therapy
Authors: Peng Zhi-Peng , Liu Xing-Chen , Ruan Yong-Hao , Jiang Da , Huang Ai-Qi , Ning Wan-Ru , Jiang Ze-Zhou , Zheng Limin , Wu Yan 
Published: February 2023

BackgroundEffects of immune checkpoint blockade (ICB) treatment in hepatocellular carcinoma (HCC) are limited. The current study explored the possibility of exploiting tumor metabolic switches to enhance HCC sensitivity to immune therapies.MethodsLevels of one-carbon (1C) metabolism and the expression of phosphoserine phosphatase (PSPH), an upstream enzyme of 1C pathway, were evaluated in paired non-tumor and tumor tissues from HCC. Underlying mechanisms mediating the role of PSPH in regulating the infiltration of monocytes/macrophages and CD8+T lymphocytes were studied through both in vitro and in vivo experiments.ResultsPSPH was significantly upregulated in tumor tissues of HCC and its levels were positively correlated with disease progression. PSPH knockdown inhibited tumor growth in immunocompetent mice, but not in those with macrophage or T lymphocyte deficiencies, indicating the pro-tumor effects of PSPH were dependent on both immune components. Mechanistically, PSPH facilitated monocytes/macrophages infiltration by inducing the production of C-C motif chemokine 2 (CCL2), while at the same time reduced CD8+T lymphocytes recruitment through inhibiting the production of C-X-C Motif Chemokine 10 (CXCL10) in tumor necrosis factor alpha (TNF-α)-conditioned cancer cells. Glutathione and S-adenosyl-methionine were partially involved in regulating the production of CCL2 and CXCL10, respectively. shPSPH(short hairpin RNA) transfection of cancer cells enhanced tumor sensitivity to anti-programmed cell death protein 1 (PD-1) therapy in vivo, and interestingly, metformin could inhibit PSPH expression in cancer cells and mimic the effects of shPSPHin sensitizing tumors to anti-PD-1 treatment.ConclusionsBy tilting the immune balance towards a tumor-friendly composition, PSPH might be useful both as a marker in stratifying patients for ICB therapy, and as an attractive therapeutic target in the treatment of human HCC.
Oral health and functional outcomes following mechanical thrombectomy for ischemic stroke
Authors: Feldman Michael J , Koester Stefan W , Chaliff Ryan S , Yengo-Kahn Aaron , Wong Gunther , Roth Steven , Longo Michael , Fusco Matthew R , Froehler Michael T , Chitale Rohan 
Published: February 2023

BackgroundAn association between poor dentition and the risk of ischemic stroke has previously been reported in the literature. In this study we assessed oral hygiene (OH), including tooth loss and the presence of dental disease, to determine if an association exists with functional outcomes following mechanical thrombectomy (MT) for large-vessel ischemic stroke.MethodsA retrospective review was conducted of consecutive adult patients at a single comprehensive stroke center who underwent MT from 2012 to 2018. Inclusion criteria included availability of CT imaging to radiographically assess OH. A multivariate analysis was performed, with the primary outcome being 90-day post-thrombectomy modified Rankin Scale (mRS) score >2.ResultsA total of 276 patients met the inclusion criteria. The average number of missing teeth was significantly higher in patients with a poor functional outcome (mean (SD) 10 (11) vs 4 (6), p<0.001). The presence of dental disease was associated with poor functional outcome, including cavities (21 (27%) vs 13 (8%), p<0.001), periapical infection (18 (23%) vs 11 (6.7%), p<0.001), and bone loss (27 (35%) vs 11 (6.7%), p<0.001). Unadjusted, missing teeth was a univariate predictor of poor outcome (OR 1.09 (95% CI 1.06 to 1.13), p<0.001). After adjustment for recanalization scores and use of tissue plasminogen activator (tPA), missing teeth remained a predictor of poor outcome (OR 1.07 (95% CI 1.03 to 1.11), p<0.001).ConclusionMissing teeth and the presence of dental disease are inversely correlated with functional independence following MT, independent of thrombectomy success or tPA status.
Decompression alone versus decompression with instrumented fusion in the treatment of lumbar degenerative spondylolisthesis: a systematic review and meta-analysis of randomised trials
Authors: Kaiser Radek , Kantorová Lucia , Langaufová Alena , Slezáková Simona , Tučková Dagmar , Klugar Miloslav , Klézl Zdeněk , Barsa Pavel , Cienciala Jan , Hajdúk Richard , Hrabálek Lumír , Kučera Roman , Netuka David , Prýmek Martin , Repko Martin , Smrčka Martin , Štulík Jan 
Published: February 2023

Objective
To determine the efficacy of adding instrumented spinal fusion to decompression to treat degenerative spondylolisthesis (DS).

Design
Systematic review with meta-analysis.

Data sources
MEDLINE, Embase, Emcare, Cochrane Library, CINAHL, Scopus, ProQuest Dissertations & Theses Global, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform from inception to May 2022.

Eligibility criteria for study selection
Randomised controlled trials (RCTs) comparing decompression with instrumented fusion to decompression alone in patients with DS. Two reviewers independently screened the studies, assessed the risk of bias and extracted data. We provide the Grading of Recommendations, Assessment, Development and Evaluation assessment of the certainty of evidence (COE).

Results
We identified 4514 records and included four trials with 523 participants. At a 2-year follow-up, adding fusion to decompression likely results in trivial difference in the Oswestry Disability Index (range 0–100, with higher values indicating greater impairment) with mean difference (MD) 0.86 (95% CI −4.53 to 6.26; moderate COE). Similar results were observed for back and leg pain measured on a scale of 0 to 100, with higher values indicating more severe pain. There was a slightly increased improvement in back pain (2-year follow-up) in the group without fusion shown by MD −5·92 points (95% CI −11.00 to −0.84; moderate COE). There was a trivial difference in leg pain between the groups, slightly favouring the one without fusion, with MD −1.25 points (95% CI −6.71 to 4.21; moderate COE). Our findings at 2-year follow-up suggest that omitting fusion may increase the reoperation rate slightly (OR 1.23; 0.70 to 2.17; low COE).

Conclusions
Evidence suggests no benefits of adding instrumented fusion to decompression for treating DS. Isolated decompression seems sufficient for most patients. Further RCTs assessing spondylolisthesis stability are needed to determine which patients would benefit from fusion.

PROSPERO registration number
CRD42022308267.