bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin Receptor Autoantibody–mediated Hypoglycemia in a Woman With Mixed Connective Tissue Disease
Authors: Petersen Max C , Graves Jonah M , Yao Tony , Schomburg Lutz , Minich Waldemar B , Parks Deborah L , McGill Janet B , Salam Maamoun 
Published: December 2021

Abstract
Autoantibodies to the insulin receptor are rare and typically cause severe insulin resistance and hyperglycemia, a condition termed type B insulin resistance. Uncommonly, antibodies to the insulin receptor can cause hypoglycemia. We present the case of a woman who developed recurrent severe hypoglycemia and myopathy, was found to have insulin receptor autoantibodies and mixed connective tissue disease, and had resolution of hypoglycemia with immunosuppression. A 55-year-old woman with a history of obesity, hypertension, and prior hemorrhagic stroke presented with recurrent severe hypoglycemia. A diagnostic fast resulted in hypoinsulinemic hypoketotic hypoglycemia. Adrenal function was intact. Progressive myopathy had developed simultaneously with her hypoglycemia, and rheumatologic evaluation revealed mixed connective tissue disease. The plasma acylcarnitine profile was normal, extensive oncologic evaluation including insulin-like growth factor 2 measurement was unrevealing, and anti-insulin antibody testing was negative. Ultimately, anti-insulin receptor antibodies were found to be present. The patient was treated with glucocorticoids and rituximab. Eight weeks after initiation of immunosuppression, the insulin receptor antibody titer had decreased and hypoglycemia had resolved. Eight months after diagnosis, the patient remained free of severe hypoglycemia despite tapering of glucocorticoids to a near-physiologic dose. Though antibodies to the insulin receptor typically cause severe insulin resistance, this patient had no evidence of insulin resistance and instead presented with recurrent severe hypoglycemia, which responded to glucocorticoids and rituximab. The diagnosis of insulin receptor antibody–mediated hypoglycemia is rare but should be considered in patients with systemic autoimmune disease, including mixed connective tissue disease, in the appropriate clinical context.
The Cross-sectional Average Inequality in Lifespan (CAL†): A Lifespan Variation Measure That Reflects the Mortality Histories of Cohorts
Authors: Nepomuceno Marília R. , Cui Qi , van Raalte Alyson , Aburto José Manuel , Canudas-Romo Vladimir 
Published: December 2021

Abstract
Lifespan variation is a key metric of mortality that describes both individual uncertainty about the length of life and heterogeneity in population health. We propose a novel and timely lifespan variation measure, which we call the cross-sectional average inequality in lifespan, or CAL†. This new index provides an alternative perspective on the analysis of lifespan inequality by combining the mortality histories of all cohorts present in a cross-sectional approach. We demonstrate how differences in the CAL† measure can be decomposed between populations by age and cohort to explore the compression or expansion of mortality in a cohort perspective. We apply these new methods using data from 10 low-mortality countries or regions from 1879 to 2013. CAL† reveals greater uncertainty in the timing of death than the period life table–based indices of variation indicate. Also, country rankings of lifespan inequality vary considerably between period and cross-sectional measures. These differences raise intriguing questions as to which temporal dimension is the most relevant to individuals when considering the uncertainty in the timing of death in planning their life courses.
Blood progenitor redox homeostasis through olfaction-derived systemic GABA in hematopoietic growth control in Drosophila
Authors: Goyal Manisha , Tomar Ajay , Madhwal Sukanya , Mukherjee Tina 
Published: December 2021

ABSTRACT
The role of reactive oxygen species (ROS) in myeloid development is well established. However, its aberrant generation alters hematopoiesis. Thus, a comprehensive understanding of events controlling ROS homeostasis forms the central focus of this study. We show that, in homeostasis, myeloid-like blood progenitor cells of the Drosophila larvae, which reside in a specialized hematopoietic organ termed the lymph gland, use TCA to generate ROS. However, excessive ROS production leads to lymph gland growth retardation. Therefore, to moderate blood progenitor ROS, Drosophila larvae rely on olfaction and its downstream systemic GABA. GABA internalization and its breakdown into succinate by progenitor cells activates pyruvate dehydrogenase kinase (PDK), which controls inhibitory phosphorylation of pyruvate dehydrogenase (PDH). PDH is the rate-limiting enzyme that connects pyruvate to the TCA cycle and to oxidative phosphorylation. Thus, GABA metabolism via PDK activation maintains TCA activity and blood progenitor ROS homeostasis, and supports normal lymph gland growth. Consequently, animals that fail to smell also fail to sustain TCA activity and ROS homeostasis, which leads to lymph gland growth retardation. Overall, this study describes the requirement of animal odor-sensing and GABA in myeloid ROS regulation and hematopoietic growth control.
Force-induced changes of α-catenin conformation stabilize vascular junctions independently of vinculin
Authors: Duong Cao Nguyen , Brückner Randy , Schmitt Martina , Nottebaum Astrid F. , Braun Laura J. , Meyer zu Brickwedde Marika , Ipe Ute , vom Bruch Hermann , Schöler Hans R. , Trapani Giuseppe , Trappmann Britta , Ebrahimkutty Mirsana P. , Huveneers Stephan , de Rooij Johan , Ishiyama Noboru , Ikura Mitsuhiko , Vestweber Dietmar 
Published: December 2021

ABSTRACT
Cadherin-mediated cell adhesion requires anchoring via the β-catenin–α-catenin complex to the actin cytoskeleton, yet, α-catenin only binds F-actin weakly. A covalent fusion of VE-cadherin to α-catenin enhances actin anchorage in endothelial cells and strongly stabilizes endothelial junctions in vivo, blocking inflammatory responses. Here, we have analyzed the underlying mechanism. We found that VE-cadherin–α-catenin constitutively recruits the actin adaptor vinculin. However, removal of the vinculin-binding region of α-catenin did not impair the ability of VE-cadherin–α-catenin to enhance junction integrity. Searching for an alternative explanation for the junction-stabilizing mechanism, we found that an antibody-defined epitope, normally buried in a short α1-helix of the actin-binding domain (ABD) of α-catenin, is openly displayed in junctional VE-cadherin–α-catenin chimera. We found that this epitope became exposed in normal α-catenin upon triggering thrombin-induced tension across the VE-cadherin complex. These results suggest that the VE-cadherin–α-catenin chimera stabilizes endothelial junctions due to conformational changes in the ABD of α-catenin that support constitutive strong binding to actin.
Priorities for research in child and adolescent anxiety and depression: a priority setting partnership with youth and professionals
Authors: Axelsdóttir Brynhildur , Eidet Lise Mette , Thoner Ragnhild , Biedilæ Sølvi , Borren Ingrid , Elvsåshagen Mari , Ludvigsen Kristine Horseng , Dahlgren Astrid 
Published: December 2021

Background: A starting point for evaluating the effectiveness of treatments should be to identify evidence gaps. Furthermore, such evaluations should consider the perspectives of patients, clinicians and carers to ensure relevance and potentially influence future research initiatives. Methods: Our approach, inspired by the James Lind Alliance methods, involved three steps. First, we performed a document analysis by identifying interventions and outcomes in two recently published overviews of systematic reviews, which summarised the effects of interventions for anxiety and depression in children and adolescents. Second, we surveyed children and adolescents with personal experiences of depression or anxiety as well as clinicians, and asked them to suggest treatments and outcomes associated with uncertainty. Finally, we facilitated a consensus process where clinicians and youth mental health patient representatives were invited to prioritise research uncertainties in separate consensus processes. Results: The survey included 674 respondents who reported a total of 1267 uncertainties. Independent coding by four investigators revealed 134 suggestions for treatments of anxiety, 90 suggestions for treatments of depression, 84 for outcomes of interventions for anxiety and 71 suggestions for outcomes of interventions for depression. Two separate priority setting workshops with eight clinicians and ten youth resulted in four independent top ten priority lists. Conclusion: Top ten lists of treatments and outcome domains of anxiety and depression in children and adolescents was identified by youth and clinicians. The results may influence the research agenda, and ultimately benefit patients.
The timing of use of risk stratification tools affects their ability to predict mortality from sepsis. A meta-regression analysis.
Authors: Flint Molly , Hamilton Fergus , Arnold David , Carlton Edward , Hettle David 
Published: December 2021

Background: Risk stratification tools (RSTs) are used in healthcare settings to identify patients at risk of sepsis and subsequent adverse outcomes. In practice RSTs are used on admission and thereafter as ‘trigger’ tools prompting sepsis management. However, studies investigating their performance report scores at a single timepoint which varies in relation to admission. The aim of this meta-analysis was to determine if the predictive performance of RSTs is altered by the timing of their use. Methods: We conducted a systematic review and meta-regression analysis of studies published from inception to 31 October 2018, using EMBASE and PubMed databases. Any cohort studies investigating the ability of an RST to predict mortality in adult sepsis patients admitted to hospital, from which a 2x2 table was available or could be constructed, were included. The diagnostic performance of RSTs in predicting mortality was the primary outcome. Sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver-operating curve (AUROC) were the primary measures, enabling further meta-regression analysis. Results: 47 studies were included, comprising 430,427 patients. Results of bivariate meta-regression analysis found tools using a first-recorded score were less sensitive than those using worst-recorded score (REML regression coefficient 0.57, 95% CI 0.07-1.08). Using worst-recorded score led to a large increase in sensitivity (summary sensitivity 0.76, 95% CI 0.67-0.83, for worst-recorded scores vs. 0.64 (0.57-0.71) for first-recorded scores). Scoring system type did not have a significant relationship with studies’ predictive ability. The most analysed RSTs were qSOFA (n=37) and EWS (n=14). Further analysis of these RSTs also found timing of their use to be associated with predictive performance. Conclusion: The timing of any RST is paramount to their predictive performance. This must be reflected in their use in practice, and lead to prospective studies in future.
Customers’ Intention to Recommend Takeaway Food during COVID-19 Pandemic
Authors: Yeni Yulia , Pujani Vera , Syahrul Laura 
Published: December 2021

Purpose: The aim of this study is to predict perceived risk and consumer willingness in recommending takeaway food from restaurant served in buffet style.
Methodology/Approach: This study used an online survey of 170 consumers who were selected based on purposive sampling method. The research questionnaire was adapted from previous research. The data were analysed using Structural Equation Modelling (SEM), with Smart PLS.
Findings: The research findings show that health risk and psychological risk have a positive effect on intention to recommend takeaway food. Meanwhile, quality risk and trust have no effect on intention to recommend takeaway food. In addition, psychological risk and quality risk have no effect on trust. This study also shows that trust does not function as a mediator of the relationship between health risk, psychological risk, quality risk, trust, and intention to recommend.
Research Limitation/Implication: This study only uses a self-report questionnaire by customers. For further research, to enrich the discussion, it is recommended to use interviews or FGD. In addition, this study only uses three risk variables. For the future, it is advisable to add other risk variables.
Originality/Value of paper: In other countries such as China, Korea and the United States, related research has been carried out, however for the context of RM Padang which is unique with all the menus served (Buffet) on the visiting customers’ table has not been found in literature.
A comparison of clinical outcomes between additional excision after unplanned and planned excisions in patients with soft-tissue sarcoma of the limb
Authors: Nakamura Tomoki , Kawai Akira , Hagi Tomohito , Asanuma Kunihiro , Sudo Akihiro 
Published: December 2021

Aims Patients with soft-tissue sarcoma (STS) who undergo unplanned excision (UE) are reported to have worse outcomes than those who undergo planned excision (PE). However, others have reported that patients who undergo UE may have similar or improved outcomes. These discrepancies are likely to be due to differences in characteristics between the two groups of patients. The aim of the study is to compare patients who underwent UE and PE using propensity score matching, by analyzing data from the Japanese Bone and Soft Tissue Tumor (BSTT) registry. Methods Data from 2006 to 2016 was obtained from the BSTT registry. Only patients with STS of the limb were included in the study. Patients with distant metastasis at the initial presentation and patients with dermatofibrosarcoma protuberans and well-differentiated liposarcoma were excluded from the study. Results A total of 4,483 patients with STS of the limb were identified before propensity score matching. There were 355 patients who underwent UE and 4,128 patients who underwent PE. The five-year disease-specific survival (DSS) rate was significantly better in the patients who received additional excision after UE than in those who underwent PE. There was no significant difference in local recurrence-free survival (LRFS) between the two groups. After propensity score matching, a new cohort of 355 patients was created for both PE and UE groups, in which baseline covariates were appropriately balanced. Reconstruction after tumour excision was frequently performed in patients who underwent additional excision after UE. There were no significant differences in DSS and LRFS between the patients who underwent PE and those who had an additional excision after UE. Conclusion Using propensity score matching, patients with STS of the limb who underwent additional excision after UE did not experience higher mortality and local failure than those who underwent PE. Reconstruction may be necessary when additional excision is performed. Cite this article: Bone Joint J 2021;103-B(12):1809–1814.
Wound photography for evaluation of surgical site infection and wound healing after lower limb trauma
Authors: Bruce Julie , Knight Ruth , Parsons Nick , Betteridge Ria , Verdon Amy , Brown Julie , Campolier Marta , Achten Juul , Costa Matt L. 
Published: December 2021

Aims Deep surgical site infection (SSI) is common after lower limb fracture. We compared the diagnosis of deep SSI using alternative methods of data collection and examined the agreement of clinical photography and in-person clinical assessment by the Centers for Disease Control and Prevention (CDC) criteria after lower limb fracture surgery. Methods Data from two large, UK-based multicentre randomized controlled major trauma trials investigating SSI and wound healing after surgical repair of open lower limb fractures that could not be primarily closed (UK WOLLF), and surgical incisions for fractures that were primarily closed (UK WHiST), were examined. Trial interventions were standard wound care management and negative pressure wound therapy after initial surgical debridement. Wound outcomes were collected from 30 days to six weeks. We compared the level of agreement between wound photography and clinical assessment of CDC-defined SSI. We are also assessed the level of agreement between blinded independent assessors of the photographs. Results Rates of CDC-defined deep SSI were 7.6% (35/460) after open fracture and 6.3% (95/1519) after closed incisional repair. Photographs were obtained for 77% and 73% of WOLLF and WHiST cohorts respectively (all participants n = 1,478). Agreement between photographic-SSI and CDC-SSI was fair for open fracture wounds (83%; k = 0.27 (95% confidence interval (CI) 0.14 to 0.42)) and for closed incisional wounds (88%; k = 0.29 (95% CI 0.20 to 0.37)) although the rate of photographically detected deep SSIs was twice as high as CDC-SSI (12% vs 6%). Agreement between different assessors for photographic-SSI (WOLLF 88%, k = 0.63 (95% CI 0.52 to 0.72); WHiST 89%; k = 0.61 (95% CI 0.54 to 0.69)); and wound healing was good (WOLLF 90%; k = 0.80 (95% CI 0.73 to 0.86); WHiST 87%; k = 0.57 (95% CI 0.50 to 0.64)). Conclusion Although wound photography was feasible within the research context and inter-rater assessor agreement substantial, digital photographs used in isolation overestimated deep SSI rates, when compared to CDC criteria. Wound photography should not replace clinical assessment in pragmatic trials but may be useful for screening purposes where surgical infection outcomes are paramount. Cite this article: Bone Joint J 2021;103-B(12):1802–1808.
Cost-effectiveness of dual-mobility components in patients with displaced femoral neck fractures
Authors: Montgomery Spencer , Bourget-Murray Jonathan , You Daniel Z. , Nherera Leo , Khoshbin Amir , Atrey Amit , Powell James Nelson 
Published: December 2021

Aims Total hip arthroplasty (THA) with dual-mobility components (DM-THA) has been shown to decrease the risk of dislocation in the setting of a displaced neck of femur fracture compared to conventional single-bearing THA (SB-THA). This study assesses if the clinical benefit of a reduced dislocation rate can justify the incremental cost increase of DM-THA compared to SB-THA. Methods Costs and benefits were established for patients aged 75 to 79 years over a five-year time period in the base case from the Canadian Health Payer’s perspective. One-way and probabilistic sensitivity analysis assessed the robustness of the base case model conclusions. Results DM-THA was found to be cost-effective, with an estimated incremental cost-effectiveness ratio (ICER) of CAD $46,556 (£27,074) per quality-adjusted life year (QALY). Sensitivity analysis revealed DM-THA was not cost-effective across all age groups in the first two years. DM-THA becomes cost-effective for those aged under 80 years at time periods from five to 15 years, but was not cost-effective for those aged 80 years and over at any timepoint. To be cost-effective at ten years in the base case, DM-THA must reduce the risk of dislocation compared to SB-THA by at least 62%. Probabilistic sensitivity analysis showed DM-THA was 58% likely to be cost-effective in the base case. Conclusion Treating patients with a displaced femoral neck fracture using DM-THA components may be cost-effective compared to SB-THA in patients aged under 80 years. However, future research will help determine if the modelled rates of adverse events hold true. Surgeons should continue to use clinical judgement and consider individual patients’ physiological age and risk factors for dislocation. Cite this article: Bone Joint J 2021;103-B(12):1783–1790.
The worldwide burden of HIV in transgender individuals: An updated systematic review and meta-analysis
Authors: Stutterheim Sarah E. , van Dijk Mart , Wang Haoyi , Jonas Kai J. 
Published: December 2021

Introduction
Transgender individuals are at risk for HIV. HIV risks are dynamic and there have been substantial changes in HIV prevention (e.g., pre-exposure prophylaxis [PrEP]). It is thus time to revisit HIV prevalence and burden among transgender individuals. The objective of this systematic review and meta-analysis was thus to examine worldwide prevalence and burden of HIV over the course of the epidemic among trans feminine and trans masculine individuals.

Methods
We conducted an updated systematic review by searching PsycINFO, PubMed, Web of Science, and Google Scholar, for studies of any research design published in in a peer-reviewed journal in any language that reported HIV prevalence among transgender individuals published between January 2000 and January 2019. Two independent reviewers extracted the data and assessed methodological quality. We then conducted a meta-analysis, using random-effects modelling, to ascertain standardized prevalence and the relative burden of HIV carried by transgender individuals by country and year of data collection, and then by geographic region. We additionally explored the impact of sampling methods and pre-exposure prophylaxis (PrEP).

Results
Based on 98 studies, overall standardized HIV prevalence over the course of the epidemic, based on weights from each country by year, was 19.9% (95% CI 14.7% - 25.1%) for trans feminine individuals (n = 48,604) and 2.56% (95% CI 0.0% - 5.9%) for trans masculine individuals (n = 6460). Overall OR for HIV infection, compared with individuals over age 15, was 66.0 (95% CI 51.4–84.8) for trans feminine individuals and 6.8 (95% CI 3.6–13.1) for trans masculine individuals. Prevalence varied by geographic region (13.5% - 29.9%) and sampling method (5.4% - 37.8%). Lastly, PrEP effects on prevalence could not be established.

Conclusion
Trans feminine and trans masculine individuals are disproportionately burdened by HIV. Their unique prevention and care needs should be comprehensively addressed. Future research should further investigate the impact of sampling methods on HIV prevalence, and monitor the potential impact of PrEP.