bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and Pharmacokinetic Exposures of First-Line Drugs Used to Treat Drug-Susceptible Tuberculosis in Children: A Systematic Review and Meta-Analysis
Authors: Solans Belén P , Béranger Agathe , Radtke Kendra , Mohamed Ali , Mirzayev Fuad , Gegia Medea , Linh Nguyen Nhat , Schumacher Samuel G , Nahid Payam , Savic Radojka M 
Published: January 2023

Abstract

Background
Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether children treated using World Health Organization–recommended or higher doses of first-line drugs achieve successful outcomes and sufficient pharmacokinetic (PK) exposures.

Methods
Titles, abstracts, and full-text articles were screened. We searched PubMed, EMBASE, CENTRAL, and trial registries from 2010 to 2021. We included studies in children aged &lt;18 years being treated for drug-susceptible tuberculosis with rifampicin (RIF), pyrazinamide, isoniazid, and ethambutol. Outcomes were treatment success rates and drug exposures. The protocol for the systematic review was preregistered in PROSPERO (no. CRD42021274222).

Results
Of 304 studies identified, 46 were eligible for full-text review, and 12 and 18 articles were included for the efficacy and PK analyses, respectively. Of 1830 children included in the efficacy analysis, 82% had favorable outcomes (range, 25%–95%). At World Health Organization–recommended doses, exposures to RIF, pyrazinamide, and ethambutol were lower in children than in adults. Children ≤6 years old have 35% lower areas under the concentration-time curve (AUCs) than older children (mean of 14.4 [95% CI 9.9–18.8] vs 22.0 [13.8–30.1] μg·h/mL) and children with human immunodeficiency virus (HIV) had 35% lower RIF AUCs than HIV-negative children (17.3 [11.4–23.2] vs 26.5 [21.3–31.7] μg·h/mL). Heterogeneity and small sample sizes were major limitations.

Conclusions
There is large variability in outcomes, with an average of 82% favorable outcomes. Drug exposures are lower in children than in adults. Younger children and/or those with HIV are underexposed to RIF. Standardization of PK pediatric studies and individual patient data analysis with safety assessment are needed to inform optimal dosing.
From ‘the land of the rising sun’ to ‘the countries of the sun’: Mishima Yukio in Greece and Italy
Authors: Zhang Xiaoxi 
Published: January 2023

AbstractThe famous Japanese author Mishima Yukio is known to have been keenly interested in ancient Greek culture. In this article, I seek to explain how his visit to Greece and Italy in the spring of 1952 intensified his philhellenism. To such an end, I will rely on Mishima’s travelogue titled Apollo’s Cup, which was published in the fall of that same year. I will pay close attention to Mishima’s encounters with the ancient ruins in Athens and with the sculptures of Antinous in the Vatican City, because they were the highlights of Mishima’s trip. I will argue that Mishima’s philhellenism was driven by his personal needs at the time and heightened by his fascination for the materiality of ancient Greece, since the ‘placeness’ of ancient Greece allowed Mishima not only to position and approach ancient Greece but also to idealize ancient Greece.
Somapacitan in children born small for gestational age: a multi-centre, open-label, controlled phase 2 study
Authors: Juul Anders , Backeljauw Philippe , Højby Michael , Kawai Masanobu , Kildemoes Rasmus Juul , Linglart Agnès , Zuckerman-Levin Nehama , Horikawa Reiko 
Published: January 2023

Abstract

Objective
Investigate efficacy, safety, and tolerability of 3 once-weekly somapacitan doses compared with daily growth hormone (GH) administration in short children born small for gestational age (SGA).

Design
Randomised, multi-centre, open-label, controlled phase 2 study comprising a 26-week main phase and a 4-year extension (NCT03878446). The study was conducted at 38 sites across 12 countries. 26-week main phase results are presented here.
Sixty-two GH treatment-naïve, prepubertal short children born SGA were randomised and exposed; 61 completed the main phase. Three somapacitan doses (0.16 [n = 12], 0.20 [n = 13], 0.24 [n = 12] mg/kg/week) and 2 daily GH doses (0.035 [n = 12], 0.067 [n = 13] mg/kg/day) were administered subcutaneously.

Results
After 26 weeks of treatment, the estimated mean annualised height velocity (HV) was 8.9, 11.0, and 11.3 cm/year for somapacitan 0.16, 0.20, and 0.24 mg/kg/week, respectively, compared to 10.3 and 11.9 cm/year for daily GH 0.035 and 0.067 mg/kg/day. Changes from baseline in HV standard deviation score (SDS), height SDS, and insulin-like growth factor I (IGF-I) SDS showed similar dose-dependent responses. Exposure-response modelling indicated the greatest efficacy correlated with the highest somapacitan exposure. Similar safety and tolerability were demonstrated for all weekly somapacitan and daily GH doses.

Conclusions
Based on the totality of data on improvements in height-based parameters combined with exposure-response analyses, somapacitan 0.24 mg/kg/week appears most efficacious, providing similar efficacy, safety, and tolerability as daily GH 0.067 mg/kg/day in short children born SGA after 26 weeks of treatment.
Institutions, Holdup, and Automation
Authors: Presidente Giorgio 
Published: January 2023

Abstract
What drives investment in automation technologies? This paper documents a positive relationship between labor-friendly institutions and investment in industrial robots in a sample of advanced and developing economies. Institutions explain a substantial share of cross-country variation in automation. The relationship between institutions and robots is stronger in sunk cost-intensive industries, where producers are vulnerable to holdup. The result suggests that one reason for producers to invest in automation is to thwart rent appropriation by labor.
Measuring the Impact of a Blood Supply Shortage Using Data Science
Authors: Bahar Burak , Gehrie Eric A , Mo Yunchuan D , Jacquot Cyril , Delaney Meghan 
Published: January 2023

Abstract

Background
Transfusion medicine is the only section of the clinical laboratory that performs diagnostic testing and dispenses a drug (blood) on the basis of those results. However, not all of the testing that informs the clinical decision to prescribe a blood transfusion is performed in the blood bank. To form a holistic assessment of blood bank responsiveness to clinical needs, it is important to be able to merge blood bank data with datapoints from the hematology laboratory and the electronic medical record.

Methods
We built an interactive visualization of the time from hemoglobin result availability to initiation of red blood cell (RBC) transfusion and monitored the result over a 2-year period that coincided with several severe blood shortages. The visualization runs entirely on free software and was designed to be feasibly deployed on a variety of hospital information technology platforms without the need for significant data science expertise.

Results
Patient factors, such as hemoglobin concentration, blood type, and presence of minor blood group antibodies influenced the time to initiation of transfusion. Time to transfusion initiation did not appear to be significantly affected by periods of blood shortage.

Conclusion
Overall, we demonstrate a proof of concept that complex, but clinically important, blood bank quality metrics can be generated with the support of a free, user-friendly system that aggregates data from multiple sources.
Technology Platforms and Approaches for Building and Evaluating Machine Learning Methods in Healthcare
Authors: Mooney Sean D 
Published: January 2023

Abstract

Background
Artificial intelligence (AI) methods are becoming increasingly commonly implemented in healthcare as decision support, business intelligence tools, or, in some cases, Food and Drug Administration–approved clinical decision-makers. Advanced lab-based diagnostic tools are increasingly becoming AI driven. The path from data to machine learning methods is an active area for research and quality improvement, and there are few established best practices. With data being generated at an unprecedented rate, there is a need for processes that enable data science investigation that protect patient privacy and minimize other business risks. New approaches for data sharing are being utilized that lower these risks.

Content
In this short review, clinical and translational AI governance is introduced along with approaches for securely building, sharing, and validating accurate and fair models. This is a constantly evolving field, and there is much interest in collecting data using standards, sharing data, building new models, evaluating models, sharing models, and, of course, implementing models into practice.

Summary
AI is an active area of research and development broadly for healthcare and laboratory testing. Robust data governance and machine learning methodological governance are required. New approaches for data sharing are enabling the development of models and their evaluation. Evaluation of methods is difficult, particularly when the evaluation is performed by the team developing the method, and should ideally be prospective. New technologies have enabled standardization of platforms for moving analytics and data science methods.
Risk Analysis for Quality Control Part 3: Practical Application of the Precision Quality Control Model
Authors: Schmidt Robert L , Moore Ryleigh A , Walker Brandon S , Rudolf Joseph W 
Published: January 2023

AbstractBackgroundWe developed a theoretical framework (Precision Quality Control [PQC]) to minimize the cost of quality, but it is not known whether the method can be applied in practice.MethodsWe used data for 2 analytes, cadmium and carbohydrate-deficient transferrin (CDT), and applied the PQC framework to find the optimal control limits. These analytes were selected because they differed with respect to sigma values that are major determinants of control limits. We explored different ways to visualize the results: (a) risk trade-off (false-positive risk vs false-negative risk), (b) cost–risk trade-off (false-positive cost vs false-negative risk), and (c) cost minimization.ResultsWe were able to use the PQC limit to produce 3 different visualizations to suggest control limits. The risk-based analysis was the simplest to apply, but the most difficult to interpret. The cost vs risk method was easy to apply but was still difficult to interpret. The cost minimization method was easy to interpret but required users to declare a willingness to pay that may be difficult to estimate.ConclusionsThe PQC method can be used to find control limits that minimize the cost of quality.
Feeding thermally processed spray-dried egg whites, singly or in combination with 15-acetyldeoxynivalenol or peroxidized soybean oil on growth performance, digestibility, intestinal morphology, and oxidative status in nursery pigs
Authors: Wilson Victoria C , McCormick Susan P , Kerr Brian J 
Published: January 2023

Abstract
Two experiments (EXP) determined the susceptibility of spray-dried egg white (SDEW) to oxidation (heating at 100 °C for 72 h; thermally processed, TP) and whether feeding TP–SDEW, 15-acetyldeoxynivalenol (15-ADON), or peroxidized soybean oil (PSO), singularly or in combination, would affect pig performance, intestinal morphology, digestibility, and markers of oxidative stress in nursery pigs. In EXP 1, 32 pigs (7.14 kg body weight, BW) were placed individually into pens and fed diets containing either 12% SDEW, 6% TP–SDEW plus 6% SDEW, or 12% TP–SDEW. Performance was measured at the end of the 24-d feeding period with biological samples harvested following euthanasia. In EXP 2, 64 pigs (10.6 kg BW) were placed individually into pens and fed diets containing 7.5% soybean oil or PSO, 10% SDEW or TP–SDEW, and diets without or with 3 mg 15-ADON/kg diet in a 2 × 2 × 2 factorial arrangement. Performance was measured at the end of the 28-d feeding period with biological samples harvested following euthanasia. In EXP 1, dietary treatment did not affect pig performance, apparent ileal digestibility of amino acids (AAs), apparent total tract digestibility (ATTD) of gross energy (GE) or nitrogen (N), ileal crypt depth, or villi height:crypt depth ratio (P &gt; 0.05). The effects of feeding TP–SDEW on protein damage in the plasma and liver (P &lt; 0.05) were variable. In EXP 2, there were no three-way interactions and only one two-way interactions among dietary treatments on parameters evaluated. There was no effect of feeding TP–SDEW on ATTD of GE or N, intestinal morphology, or on oxidative markers in the plasma, liver, or ileum (P &gt; 0.05). There was no effect of feeding diets containing added 15-ADON on ATTD of GE, ileal AA digestibility, intestinal morphology, oxidative markers in the plasma, liver, or ileum, or pig performance (P &gt; 0.05). Feeding pigs diets containing PSO resulted in reduced ATTD of GE and N, plasma vitamin E concentration, and pig performance (P &lt; 0.01) but did not affect intestinal morphology or oxidative markers in the liver or ileum (P &gt; 0.05). In conclusion, it was difficult to induce protein oxidation in SDEW and when achieved there were limited effects on performance, digestibility, intestinal morphology, and oxidative status. Furthermore, singly adding 15-A-DON to a diet had no effect on the animal. At last, adding PSO reduces animal performance, but has limited effect on digestibility, intestinal morphology, and oxidative status in nursery pigs.
Global Patterns of Insect Resistance to Transgenic Bt Crops: The First 25 Years
Authors: Tabashnik Bruce E , Fabrick Jeffrey A , Carrière Yves 
Published: January 2023

Abstract
Crops genetically engineered to produce insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) have improved pest management and reduced reliance on insecticide sprays. However, evolution of practical resistance by some pests has reduced the efficacy of Bt crops. We analyzed global resistance monitoring data for 24 pest species based on the first 25 yr of cultivation of Bt crops including corn, cotton, soybean, and sugarcane. Each of the 73 cases examined represents the response of one pest species in one country to one Bt toxin produced by one or more Bt crops. The cases of practical resistance rose from 3 in 2005 to 26 in 2020. Practical resistance has been documented in some populations of 11 pest species (nine lepidopterans and two coleopterans), collectively affecting nine widely used crystalline (Cry) Bt toxins in seven countries. Conversely, 30 cases reflect no decrease in susceptibility to Bt crops in populations of 16 pest species in 10 countries. The remaining 17 cases provide early warnings of resistance, which entail genetically based decreases in susceptibility without evidence of reduced field efficacy. The early warnings involve four Cry toxins and the Bt vegetative insecticidal protein Vip3Aa. Factors expected to favor sustained susceptibility include abundant refuges of non-Bt host plants, recessive inheritance of resistance, low resistance allele frequency, fitness costs, incomplete resistance, and redundant killing by multi-toxin Bt crops. Also, sufficiently abundant refuges can overcome some unfavorable conditions for other factors. These insights may help to increase the sustainability of current and future transgenic insecticidal crops.
Clinical Applications of the History of Medicine in Muslim-Majority Nations
Authors: Weber Alan S 
Published: January 2023

Abstract
Since the early twentieth century, a number of physicians and professional historians have argued for the integration of the history of medicine into both medical education and clinical practice. After the supplanting of the humoral model of medicine in favor of the germ theory of disease in the late nineteenth century, medical school administrators have repeatedly asked medical historians for their rationale for studying “outdated science” in medical training programs beyond antiquarianism and knowledge for knowledge’s sake. However, a number of arguments can be adduced for the use and relevance of the history of medicine, including the observations that history: 1) provides examples of inspiring or highly ethical individuals who can serve as role models in practitioner identity formation; 2) helps to develop critical analytical skills and other modes of humanistic thought and behavior directly relevant to patient care (e.g., empathy); 3) promotes culturally-competent care, since history informs culture; 4) encourages inquiry into the sociocultural factors that affect the development of modern medical ecosystems; 5) provides a philosophical tradition for critiquing ethics in the medical profession. This contribution specifically traces the potential uses of Islamic medical history in the clinic and medical schools in Muslim-majority countries, primarily in the Middle East.
Straightforward? Family Reunification for Refugees in France: Aligning Legal Standards, Institutional Practices and Procedural Guarantees
Authors: Meyer Antoine P G 
Published: January 2023

Abstract
This article addresses family reunification in France (réunification familiale) as an essential right of refugees and a clear legal entitlement under domestic law. It proceeds with a reality-check on access to the designated visa for families and support professionals and discusses potential grounds for future advocacy on the matter. Available data, reports and complementary feedback gained from several practitioners in the field suggest hurdles stand in both law and practice, at odds with international standards and guidance. Strengthening information, physical and financial access to the procedure and ensuring due diligence, flexibility and transparency when examining applications arguably remain on the agenda for reform. Further adjustments to both administrative and judicial options for appeal and legal aid rules could also upgrade guarantees for families, with greater chances for an effective remedy in a timeframe compatible with the stakes. Filling standing gaps in data, research and evaluation would seem equally essential for an evidence-based debate, and in calling for a proactive reunification policy that acts on its potential as a pathway towards international protection. Ultimately, while a reminder of the multiple dimensions to investigate if one is concerned with effective access to reunification beyond its legal consecration as a right, the ‘French case’ certainly illustrates the need for advocates in this field to keep widening strategies and tools, besides litigation.
The CD16 and CD32b Fc-gamma receptors regulate antibody-mediated responses in mouse natural killer cells
Authors: Aguilar Oscar A , Gonzalez-Hinojosa Maria D R , Arakawa-Hoyt Janice S , Millan Alberto J , Gotthardt Dagmar , Nabekura Tsukasa , Lanier Lewis L 
Published: January 2023

Abstract
Natural killer (NK) cells are innate lymphocytes capable of mediating immune responses without prior sensitization. NK cells express Fc-gamma receptors (FcγRs) that engage the Fc region of IgG. Studies investigating the role of FcγRs on mouse NK cells have been limited due to lack specific reagents. In this study, we characterize the expression and biological consequences of activating mouse NK cells through their FcγRs. We demonstrate that most NK cells express the activating CD16 receptor, and a subset of NK cells also expresses the inhibitory CD32b receptor. Critically, these FcγRs are functional on mouse NK cells and can modulate antibody-mediated responses. We also characterized mice with conditional knockout alleles of Fcgr3 (CD16) or Fcgr2b (CD32b) in the NK and innate lymphoid cell (ILC) lineage. NK cells in these mice did not reveal any developmental defects and were responsive to cross-linking activating NK receptors, cytokine stimulation, and killing of YAC-1 targets. Importantly, CD16-deficient NK cells failed to induce antibody-directed cellular cytotoxicity of antibody-coated B-cell lymphomas in in vitro assays. In addition, we demonstrate the important role of CD16 on NK cells using an in vivo model of cancer immunotherapy using anti-CD20 antibody treatment of B-cell lymphomas.
Prostate cancer disparities among American Indians and Alaskan Natives in the United States
Authors: Chu Carissa E , Leapman Michael S , Zhao Shoujun , Cowan Janet E , Washington Samuel L , Cooperberg Matthew R 
Published: January 2023

AbstractBackgroundAmericans Indians and Alaska Natives face disparities in cancer care with lower rates of screening, limited treatment access, and worse survival. Prostate cancer treatment access and patterns of care remain unknown.MethodsWe used Surveillance, Epidemiology, and End Results data to compare incidence, primary treatment, and cancer-specific mortality across American Indian and Alaska Native, Asian and Pacific Islander, Black, and White patients. Baseline characteristics included prostate-specific antigen (PSA), Gleason score (GS), tumor stage, 9-level Cancer of the Prostate Risk Assessment risk score, county characteristics, and health-care provider density. Primary outcomes were first definitive treatment and prostate cancer-specific mortality (PCSM).ResultsAmerican Indian and Alaska Native patients were more frequently diagnosed with higher PSA, GS greater than or equal or 8, stage greater than or equal to cT3, high-risk disease overall (Cancer of the Prostate Risk Assessment risk score ≥ 6), and metastases at diagnosis than any other group. Adjusting for age, PSA, GS, and clinical stage, American Indian or Alaska Native patients with localized prostate cancer were more likely to undergo external beam radiation than radical prostatectomy and had the highest rates of no documented treatment. Five-year PCSM was higher among American Indian and Alaska Natives than any other racial group. However, after multivariable adjustment accounting for clinical and pathologic factors, county-level demographics, and provider density, American Indian and Alaska Native patient PCSM hazards were no different than those of White patients.ConclusionsAmerican Indian or Alaska Native patients have more advanced prostate cancer, lower rates of definitive treatment, higher mortality, and reside in areas of less specialty care. Disparities in access appear to account for excess risks of PCSM. Focused health policy interventions are needed to address these disparities.
Competing over the continental shelf: the legal versus the geophysical entitlements
Authors: Salas Kantor Benjamin , Valdivia Torres Carolina 
Published: January 2023

Abstract
For the past decades, international courts and tribunals have eluded the question of whether a State’s entitlement to a continental shelf beyond 200 nautical miles (nm) may extend within 200 nm of another State. The opacity around this question steered the International Court of Justice to surprisingly divide its oral proceedings in the pending dispute between Nicaragua and Colombia, so that it could address this legal predicament first. In similar circumstances, the International Tribunal for the Law of the Sea asked Mauritius and The Maldives to deal with the same question. While this is not the first time an international court or tribunal is asked to delimit a continental shelf beyond 200 nm, it will be the first where the ‘legal’ and the ‘geophysical’ entitlements enshrined in Article 76(1) of UNCLOS face each other. This article examines the current state of international law and proposes that the overlap between both entitlements is legally permissible, but the ‘legal’ entitlement enjoys further normative strength and will guide the equitable delimitation of the continental shelf.