bluuebunny/crossref_metadata_2025_split huggingface dataset:
Numerical estimation of a tsunami source at the flexural area of Kuril and Japan Trenches in the fifteenth to seventeenth century based on paleotsunami deposit distributions in northern Japan
Authors: Sato Kai , Yamada Masaki , Ishimura Daisuke , Ishizawa Takashi , Baba Toshitaka 
Published: December 2022

AbstractPaleotsunami deposit investigations and numerical tsunami computations have been performed to elucidate the source and size of large tsunamis along the Kuril to Japan Trenches, particularly for unusual tsunamis that occurred in the seventeenth century, the 1611 CE Keicho tsunami (M 8.1) along the Japan Trench and seventeenth-century tsunami (> Mw 8.8) along the Kuril Trench, which caused serious damages on the coastal residents and environments. Moreover, several paleotsunami deposits dating from the thirteenth to eighteenth centuries have been reported along the area between the Kuril and Japan subduction zones, but their sources have not been clarified. In this study, we estimated the tsunami sources from numerical simulations using the distribution of fifteenth- to seventeenth-century tsunami deposits at Sekinehama along the coast of the Shimokita Peninsula. Based on numerical simulations with previously proposed fault models, the tsunami deposits showing similar ages at Sekinehama and another site on the coast of Shimokita Peninsula, which are within 50 km apart, could not be explained except with the huge earthquake models (> Mw 9.1), whose rupture zones extend to not only the Kuril or Japan Trenches but also their flexural area. Thus, we modified or newly proposed twelve fault models located in the flexural area between the two trenches to explain tsunami deposits possibly around the seventeenth century at the above-mentioned two sites on the coast of Shimokita Peninsula. Simulations using these models elucidated that the rupture in the shallow or deep plate boundaries with > 14–32 m slip (> Mw 8.55–8.76) is necessary. If the tsunami deposits around the seventeenth century along the Iburi–Hidaka coast in Hokkaido and those at the two sites mentioned above might be left by an identical event, an interplate earthquake with > 18–40 m slip (> Mw 8.62–9.2) in the flexural area is needed. Moreover, this interplate earthquake might have occurred in the deep plate boundary than in the shallower plate boundary based on slip deficit and slow earthquake distribution data. Our results offer significant insights into a large earthquake (> M 8) along the Kuril and Japan Trenches in the fifteenth to seventeenth century.
Food safety practice and its associated factors among food handlers in food establishments of Mettu and Bedelle towns, Southwest Ethiopia, 2022
Authors: Tamiru Sanbato , Bidira Kebebe , Moges Tesema , Dugasa Milkias , Amsalu Bonsa , Gezimu Wubishet 
Published: December 2022

Abstract
Background
Food safety and hygiene are currently a global health concern, especially in unindustrialized countries, as a result of increasing food-borne diseases (FBDs) and accompanying deaths. It has continued to be a critical problem for people, food companies, and food control officials in developed and developing nations.

Objective
The objective of the study was to assess food safety practices and associated factors among food handlers in food establishments in Mettu and Bedelle towns, south-west Ethiopia, 2022.

Methods
A community-based cross-sectional study was conducted from February to March 2022, among 450 randomly selected food handlers working in food and drink establishments in Mettu and Bedelle towns, Southwest Ethiopia. Data was collected using an interviewer-administered structured questionnaire. The data was coded and entered into Epi Data version 3.1 before being exported to SPSS version 20 for analysis. Both bivariate and multivariable logistic regression models were fitted. An adjusted odds ratio and a 95% confidence level were estimated to assess the significance of associations. A p-value of < 0.05 was considered sufficient to declare the statistical significance of variables in the final model.

Result
A total of 450 food handlers participated in the study, making the response rate 99.3%. About 202 (44.9%) of respondents had poor practices in food safety. Lack of supervision (AOR = 6.2, 95% CI: 3.37, 11.39), absence of regular medical checkups (AOR = 1.98; 95% CI: 1.14, 3.43), lack of knowledge of food safety practices (AOR =2.32; 95% CI: 1.38, 3.89), availability of water storage equipment (AOR =0.37; CI: 0.21, 0.64), and unavailability of a refrigerator (AOR =0.24; 95% CI: 0.12) were factors significantly associated with food safety practices.

Conclusion
The level of poor food safety practices was remarkably high. Knowledge of food safety, medical checkups, service year as food handler, availability of water storage equipment, availability of refrigerator, and sanitary supervision were all significantly associated with food safety practice. Hence, great efforts are needed to improve food safety practices, and awareness should be created for food handlers on food safety.
Targeted validation: validating clinical prediction models in their intended population and setting
Authors: Sperrin Matthew , Riley Richard D. , Collins Gary S. , Martin Glen P. 
Published: December 2022

AbstractClinical prediction models must be appropriately validated before they can be used. While validation studies are sometimes carefully designed to match an intended population/setting of the model, it is common for validation studies to take place with arbitrary datasets, chosen for convenience rather than relevance. We call estimating how well a model performs within the intended population/setting “targeted validation”. Use of this term sharpens the focus on the intended use of a model, which may increase the applicability of developed models, avoid misleading conclusions, and reduce research waste. It also exposes that external validation may not be required when the intended population for the model matches the population used to develop the model; here, a robust internal validation may be sufficient, especially if the development dataset was large.
The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development
Authors: Yan Weizhu , Zheng Yanhui , Dou Chao , Zhang Guixiang , Arnaout Toufic , Cheng Wei 
Published: December 2022

AbstractMycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a tenacious pathogen that has latently infected one third of the world’s population. However, conventional TB treatment regimens are no longer sufficient to tackle the growing threat of drug resistance, stimulating the development of innovative anti-tuberculosis agents, with special emphasis on new protein targets. The Mtb genome encodes ~4000 predicted proteins, among which many enzymes participate in various cellular metabolisms. For example, more than 200 proteins are involved in fatty acid biosynthesis, which assists in the construction of the cell envelope, and is closely related to the pathogenesis and resistance of mycobacteria. Here we review several essential enzymes responsible for fatty acid and nucleotide biosynthesis, cellular metabolism of lipids or amino acids, energy utilization, and metal uptake. These include InhA, MmpL3, MmaA4, PcaA, CmaA1, CmaA2, isocitrate lyases (ICLs), pantothenate synthase (PS), Lysine-ε amino transferase (LAT), LeuD, IdeR, KatG, Rv1098c, and PyrG. In addition, we summarize the role of the transcriptional regulator PhoP which may regulate the expression of more than 110 genes, and the essential biosynthesis enzyme glutamine synthetase (GlnA1). All these enzymes are either validated drug targets or promising target candidates, with drugs targeting ICLs and LAT expected to solve the problem of persistent TB infection. To better understand how anti-tuberculosis drugs act on these proteins, their structures and the structure-based drug/inhibitor designs are discussed. Overall, this investigation should provide guidance and support for current and future pharmaceutical development efforts against mycobacterial pathogenesis.
Patient and Physician Decisional Factors Regarding Hypercalcemia of Malignancy Treatment: A Novel Mixed-Methods Study
Authors: Bassatne Aya , Murad Mohammad H , Piggott Thomas , Drake Matthew T , Rahme Maya , El-Hajj Fuleihan Ghada 
Published: December 2022

AbstractBackgroundIntegrating shared decision making between patients and physicians and incorporating their values and preferences in the development of clinical practice guidelines (CPGs) is of critical importance to optimize CPG implementation and treatment adherence. This applies to many debilitating diseases, including hypercalcemia of malignancy (HCM).ObjectiveEvaluate patient and physician values, preferences, and attitudes to better inform CPGs to treat HCM in adults.MethodsWe followed a mixed-methods approach. We conducted a systematic review using 5 databases to identify studies reporting on patient and physician values, costs and resources, feasibility, acceptability, and equity regarding HCM treatment. We also gathered data from different countries on the cost of multiple treatment modalities. We collected data on outcome prioritization from the CPG Working Group. Similarly, we collected data from patients with HCM regarding outcome prioritization and administered a questionnaire to evaluate their attitudes and perceptions toward treatment as well as treatment acceptability and feasibility.ResultsIn the systematic review, we included 2 cross-sectional surveys conducted on the same population of physicians who agreed that treating HCM alleviates symptoms and improves quality of life; however, harms and benefits should be thoroughly considered when deciding on the duration of treatment. We also included 2 studies on cost showing that intravenous (IV) bisphosphonate is more cost-effective than a combination of IV bisphosphonate and calcitonin and administration of IV zoledronic acid at home is more cost-effective than other IV bisphosphonates. The cost of zoledronic acid, denosumab, and cinacalcet varied widely among countries and types (brand vs generic). Both the CPG Working Group and patients with HCM agreed that the most important outcomes when deciding on treatment were survival and resolution of HCM, but there was some variability in the ratings for other outcomes.ConclusionUsing mixed methods, CPG developers can obtain meaningful information regarding evidence to decision criteria. In the case of HCM CPGs, this approach has provided the required contextual information and supported the development of evidence-based recommendations.
A Systematic Review Supporting the Endocrine Society Clinical Practice Guideline on the Treatment of Hypercalcemia of Malignancy in Adults
Authors: Seisa Mohamed O , Nayfeh Tarek , Hasan Bashar , Firwana Mohammed , Saadi Samer , Mushannen Ahmed , Shah Sahrish H , Rajjoub Noora S , Farah Magdoleen H , Prokop Larry J , Wang Zhen , Fuleihan Ghada El-Hajj , Drake Matthew T , Murad Mohammad Hassan 
Published: December 2022

AbstractContextHypercalcemia is a common complication of malignancy that is associated with high morbidity and mortality.ObjectiveTo support development of the Endocrine Society Clinical Practice Guideline for the treatment of hypercalcemia of malignancy in adults.MethodsWe searched multiple databases for studies that addressed 8 clinical questions prioritized by a guideline panel from the Endocrine Society. Quantitative and qualitative synthesis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess certainty of evidence.ResultsWe reviewed 1949 citations, from which we included 21 studies. The risk of bias for most of the included studies was moderate. A higher proportion of patients who received bisphosphonate achieved resolution of hypercalcemia when compared to placebo. The incidence rate of adverse events was significantly higher in the bisphosphonate group. Comparing denosumab to bisphosphonate, there was no significant difference in the rate of patients who achieved resolution of hypercalcemia. Two-thirds of patients with refractory/recurrent hypercalcemia of malignancy who received denosumab following bisphosphonate therapy achieved resolution of hypercalcemia. Addition of calcitonin to bisphosphonate therapy did not affect the resolution of hypercalcemia, time to normocalcemia, or hypocalcemia. Only indirect evidence was available to address questions on the management of hypercalcemia in tumors associated with high calcitriol levels, refractory/recurrent hypercalcemia of malignancy following the use of bisphosphonates, and the use of calcimimetics in the treatment of hypercalcemia associated with parathyroid carcinoma. The certainty of the evidence to address all 8 clinical questions was low to very low.ConclusionThe evidence summarized in this systematic review addresses the benefits and harms of treatments of hypercalcemia of malignancy. Additional information about patients’ values and preferences, and other important decisional and contextual factors is needed to facilitate the development of clinical recommendations.
β-Cell Function and Insulin Sensitivity in Youth With Early Type 1 Diabetes From a 2-Hour 7-Sample OGTT
Authors: Galderisi Alfonso , Evans-Molina Carmella , Martino Mariangela , Caprio Sonia , Cobelli Claudio , Moran Antoinette 
Published: December 2022

Abstract

Context
The oral minimal model is a widely accepted noninvasive tool to quantify both β-cell responsiveness and insulin sensitivity (SI) from glucose, C-peptide, and insulin concentrations during a 3-hour 9-point oral glucose tolerance test (OGTT).

Objective
Here, we aimed to validate a 2-hour 7-point protocol against the 3-hour OGTT and to test how variation in early sampling frequency impacts estimates of β-cell responsiveness and SI.

Methods
We conducted a secondary analysis on 15 lean youth with stage 1 type 1 diabetes (T1D; ≥ 2 islet autoantibodies with no dysglycemia) who underwent a 3-hour 9-point OGTT. The oral minimal model was used to quantitate β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI = φtotal × SI). Seven- and 5-point 2-hour OGTT protocols were tested against the 3-hour 9-point gold standard to determine agreement between estimates of φtotal and its dynamic and static components, SI, and DI across different sampling strategies.

Results
The 2-hour estimates for the disposition index exhibited a strong correlation with 3-hour measures (r = 0.975; P &lt; .001) with similar results for β-cell responsiveness and SI (r = 0.997 and r = 0.982; P &lt; .001, respectively). The agreement of the 3 estimates between the 7-point 2-hour and 9-point 3-hour protocols fell within the 95% CI on the Bland-Altman grid with a median difference of 16.9% (−35.3 to 32.5), 0.2% (−0.6 to 1.3), and 14.9% (−1.4 to 28.3) for DI, φtotal, and SI. Conversely, the 5-point protocol did not provide reliable estimates of φ dynamic and static components.

Conclusion
The 2-hour 7-point OGTT is reliable in individuals with stage 1 T1D for assessment of β-cell responsiveness, SI, and DI. Incorporation of these analyses into current 2-hour diabetes staging and monitoring OGTTs offers the potential to more accurately quantify risk of progression in the early stages of T1D.
Low T3 Syndrome on Admission and Response to Nutritional Support in Malnourished Medical Inpatients
Authors: Müller Natasha Anouschka , Kaegi-Braun Nina , Durmisi Mirsada , Gressies Carla , Tribolet Pascal , Stanga Zeno , Mueller Beat , Schuetz Philipp 
Published: December 2022

Abstract

Context
During illness, deiodination of thyroxine (T4) to triiodothyronine (T3) is downregulated. This is called “low T3 syndrome”, an adaptive metabolic mechanism to reduce energy expenditure and prevent catabolism.

Objective
We aimed to investigate the prognostic role of low T3 syndrome in patients at nutritional risk regarding mortality, clinical outcomes, and response to nutritional support.

Methods
This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled, Swiss, multicenter trial comparing effects of individualized nutritional support with usual care in adult medical inpatients at nutritional risk. The primary endpoint was all-cause mortality over 30, 180 days, and 5 years.

Results
We had complete data including fT3 concentration of 801/2028 (39.5%) patients from the initial trial. Of these 492 (61.4%) had low T3 syndrome (fT3 &lt; 3.2 pmol/L). Low T3 syndrome was associated with higher mortality over 30 days (adjusted hazard ratio 1.97, 95% CI 1.17-3.31, P = .011) and other adverse clinical outcomes. Nutritional support only lowered mortality in the group of patients with low T3 syndrome but not in those without low T3 syndrome (adjusted odds ratio of nutritional support of 0.82 [95% CI 0.47-1.41] vs 1.47 [95% CI 0.55-3.94]). This finding, however, was not significant in interaction analysis (P for interaction = .401).

Conclusion
Our secondary analysis of a randomized trial suggests that medical inpatients at nutritional risk with low T3 syndrome have a substantial increase in mortality and may show a more pronounced beneficial response to nutritional support interventions.
Accumulation in Visceral Adipose Tissue Over 6 Years Is Associated With Lower Paraspinal Muscle Density
Authors: Liu Ching-Ti , Tsai Timothy , Allaire Brett T , Bouxsein Mary L , Hannan Marian T , Travison Thomas G , Kiel Douglas P 
Published: December 2022

Abstract

Context
Visceral adipose tissue (VAT) has been recognized to be a metabolically active fat depot that may have paracrine effects on surrounding tissues, including muscle. Since many adults accumulate VAT as they age, the effect of changes in VAT on muscle is of interest.

Objective
We determined the association between 6-year changes in VAT and paraspinal muscle density, an indicator of fatty infiltration.

Methods
This study included 1145 participants from the Framingham Study third-generation cohort who had both quantitative computed tomography scans of the spine at baseline and 6-year's follow-up, on whom muscle density was measured along with VAT. We implemented multiple regression to determine the association of muscle density at follow-up as primary outcome measure with changes in VAT (follow-up minus baseline divided by 100), adjusting for VAT at baseline, age, sex, height, menopausal status, presence of diabetes, and physical activity. Analyses were performed in men and women separately.

Results
After adjustment for covariates, individuals with the greatest accumulation of VAT over 6 years had significantly lower paraspinal density at the follow-up with an estimated 0.302 (95% CI, −0.380 to −0.224) and 0.476 (95% CI: −0.598 to −0.354) lower muscle density (HU) per 100-cm3 increase in VAT (both P values &lt; .001) in men and women, respectively.

Conclusion
These results highlight that age-related accumulation of VAT in men and women is associated with lower muscle density. VAT may represent a modifiable risk factor for poor musculoskeletal outcomes with aging.
New Insights into the Structure and Function of Class B1 GPCRs
Authors: Cary Brian P , Zhang Xin , Cao Jianjun , Johnson Rachel M , Piper Sarah J , Gerrard Elliot J , Wootten Denise , Sexton Patrick M 
Published: December 2022

Abstract
G protein–coupled receptors (GPCRs) are the largest family of cell surface receptors. Class B1 GPCRs constitute a subfamily of 15 receptors that characteristically contain large extracellular domains (ECDs) and respond to long polypeptide hormones. Class B1 GPCRs are critical regulators of homeostasis, and, as such, many are important drug targets. While most transmembrane proteins, including GPCRs, are recalcitrant to crystallization, recent advances in cryo-electron microscopy (cryo-EM) have facilitated a rapid expansion of the structural understanding of membrane proteins. As a testament to this success, structures for all the class B1 receptors bound to G proteins have been determined by cryo-EM in the past 5 years. Further advances in cryo-EM have uncovered dynamics of these receptors, ligands, and signaling partners. Here, we examine the recent structural underpinnings of the class B1 GPCRs with an emphasis on structure–function relationships.
Clinical, Pathophysiologic, Genetic, and Therapeutic Progress in Primary Bilateral Macronodular Adrenal Hyperplasia
Authors: Bertherat Jérôme , Bourdeau Isabelle , Bouys Lucas , Chasseloup Fanny , Kamenický Peter , Lacroix André 
Published: December 2022

AbstractPatients with primary bilateral macronodular adrenal hyperplasia (PBMAH) usually present bilateral benign adrenocortical macronodules at imaging and variable levels of cortisol excess. PBMAH is a rare cause of primary overt Cushing's syndrome but may represent up to one-third of bilateral adrenal incidentalomas with evidence of cortisol excess. The increased steroidogenesis in PBMAH is often regulated by various G protein–coupled receptors (GPCRs) aberrantly expressed in PBMAH tissues; some receptor ligands are ectopically produced in PBMAH tissues, creating aberrant autocrine/paracrine regulation of steroidogenesis.The bilateral nature of PBMAH and familial aggregation led to the identification of germline heterozygous inactivating mutations of the ARMC5 gene, in 20% to 25% of the apparent sporadic cases and more frequently in familial cases; ARMC5 mutations/pathogenic variants can be associated with meningiomas. More recently, combined germline mutations/pathogenic variants and somatic events inactivating the KDM1A gene were specifically identified in patients affected by glucose-dependent insulinotropic peptide (GIP)-dependent PBMAH. Functional studies demonstrated that inactivation of KDM1A leads to GIP-receptor (GIPR) overexpression and over- or downregulation of other GPCRs. Genetic analysis is now available for early detection of family members of index cases with PBMAH carrying identified germline pathogenic variants. Detailed biochemical, imaging, and comorbidity assessment of the nature and severity of PBMAH is essential for its management. Treatment is reserved for patients with overt or mild cortisol/aldosterone or other steroid excesses, taking in account comorbidities. It previously relied on bilateral adrenalectomy; however, recent studies tend to favor unilateral adrenalectomy or, less frequently, medical treatment with cortisol synthesis inhibitors or specific blockers of aberrant GPCR.