bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of MRI-derived kidney volume, kidney function, body composition and physical performance in ≈38 000 UK Biobank participants: a population-based observational study
Authors: Cho Jeong Min , Koh Jung Hun , Kim Seong Geun , Lee Soojin , Kim Yaerim , Cho Semin , Kim Kwangsoo , Kim Yong Chul , Han Seung Seok , Lee Hajeong , Lee Jung Pyo , Joo Kwon Wook , Lim Chun Soo , Kim Yon Su , Kim Dong Ki , Park Sehoon
Published: March 2024

Background

Kidney volume is used as a predictive and therapeutic marker for several clinical conditions. However, there is a lack of large-scale studies examining the relationship between kidney volume and various clinicodemographic factors, including kidney function, body composition and physical performance.

Methods

In this observational study, MRI-derived kidney volume measurements from 38 526 UK Biobank participants were analysed. Major kidney volume–related measures included body surface area (BSA)-adjusted total kidney volume (TKV) and the difference in bilateral kidneys. Multivariable-adjusted linear regression and cubic spline analyses were used to explore the association between kidney volume–related measures and clinicodemographic factors. Cox or logistic regression was used to identify the risks of death, non-kidney cancer, myocardial infarction, ischaemic stroke and chronic kidney disease (CKD).

Results

The median of BSA-adjusted TKV and the difference in kidney volume were 141.9 ml/m2 [interquartile range (IQR) 128.1–156.9] and 1.08-fold (IQR 1.04–1.15), respectively. Higher BSA-adjusted TKV was significantly associated with higher estimated glomerular filtration rate {eGFR; β = 0.43 [95% confidence interval (CI) 0.42–0.44]; P < .001}, greater muscle volume [β = 0.50 (95% CI 0.48–0.51); P < .001] and greater mean handgrip strength [β = 0.15 (95% CI 0.13–0.16); P < .001] but lower visceral adipose tissue volume [VAT; β = −0.09 (95% CI −0.11 to −0.07); P < .001] in adjusted models. A greater difference in bilateral kidney volumes was associated with lower eGFR, muscle volume and physical performance but with higher proteinuria and VAT. Higher BSA-adjusted TKV was significantly associated with a reduced risk of CKD [odds ratio (OR) 0.7 (95% CI 0.63–0.77); P < .001], while a greater difference in kidney volume was significantly associated with an increased risk of CKD [OR 1.13 (95% CI 1.07–1.20); P < .001].

Conclusion

Higher BSA-adjusted TKV and lower differences in bilateral kidney volumes are associated with higher kidney function, muscle volume and physical performance and a reduced risk of CKD.
Ex vivo evaluation of 3 different right ventricular outflow tract substitutes
Authors: Saisho Hiroyuki , Geisler Ioana , Scharfschwerdt Michael , Sadat Najla , Zhang Xiling , Puehler Thomas , Ensminger Stephan , Fujita Buntaro , Aboud Anas
Published: March 2024

OBJECTIVES

The Ross procedure represents an excellent treatment option in younger patients with aortic stenosis but is limited by poor availability of homografts. In this study, we investigated the hydrodynamic performance of 3 different types of right ventricular outflow tract replacement with pericardium or synthetic material.

METHODS

Three different types of valved conduits were constructed using pericardium and/or synthetic material (Group PEPE: pericardial cusps and pericardial conduit, Group PEPR: pericardial cusps and Dacron conduit, Group PRPR: expanded polytetrafluoroethylene cusps and Dacron conduit). The conduits were designed according to the Ozaki method. Their hydrodynamic performance (effective orifice area, mean pressure gradient and leakage volume) were evaluated in a mock circulation loop at different hydrodynamic conditions.

RESULTS

Hydrodynamic assessment showed significantly larger effective orifice area of PEPE and PEPR compared to PRPR under all conditions and there were no significant differences between PEPE and PEPR [for condition 2: PEPE 2.43 (2.35–2.54) cm2, PEPR: 2.42 (2.4–2.5) cm2, PRPR: 2.08 (1.97–2.21) cm2, adjusted pairwise comparisons: PEPE versus PEPR: P = 0.80, PEPE versus PRPR: P  < 0.001, PEPR versus PRPR: P  < 0.001]. Mean pressure gradient was significantly lower for PEPE and PEPR compared with PRPR, whereas no significant differences were seen between PEPE and PEPR. Leakage volume was significantly lower for PEPE and PEPR compared with PRPR under all conditions while leakage was similar between PEPE and PEPR.

CONCLUSIONS

Pulmonary graft reconstruction with pericardium cusps showed superior hydrodynamic performance compared with polytetrafluoroethylene cusps. Our results suggest that it could be considered as an alternative substitute for right ventricular outflow tract replacement during the Ross procedure.
Chest tube removal at different gas flows in prolonged air leak: a randomized non-inferiority trial
Authors: Li Xinyang , Yang Hang , Cai Yongsheng , Ye Xin , Chen Qirui , Ji Ying , Wang Jing , Fu Yili , Hu Bin , Miao Jinbai
Published: March 2024

OBJECTIVES

To evaluate the safety and feasibility of removing drainage tubes at larger size of air leak in patients with prolonged air leak after pulmonary surgery.

METHODS

Ninety-five patients who underwent pulmonary surgery with prolonged air leak in our centre were enrolled in this randomized controlled, single-centre, non-inferiority study. The drainage tube was clamped with a stable size of air leak observed over the last 6 h, which was quantified by gas flow rate using the digital drainage system. The control group (n = 48) and the study group (n = 46) had their drainage tube clamped at 0–20 ml/min and 60–80 ml/min, respectively. We continuously monitored clinical symptoms, conducted imaging and laboratory examinations, and decided whether to reopen the drainage tube.

RESULTS

The reopening rate in the study group was not lower than that in the control group (2.08% vs 6.52%, P > 0.05). The absolute difference in reopening rate was 4.44% (95% confidence interval –0.038 to 0.126), with an upper limit of 12.6% below the non-inferiority margin (15%). There were significant differences in the length of stay [16.5 (13–24.75) vs 13.5 (12–19.25), P = 0.017] and the duration of drainage [12 (9.25–18.50) vs 10 (8–12.25), P = 0.007] between the control and study groups. No notable differences were observed in chest X-ray results 14 days after discharge or in the readmission rate.

CONCLUSIONS

For patients with prolonged air leak, removing drainage tubes at larger size of air leak demonstrated similar safety compared to smaller size of air leak, and can shorten both length of stay and drainage duration.

Clinical trial registration number

Name of registry: Gas flow threshold for safe removal of chest drainage in patients with alveolar-pleural fistula prolonged air leak after pulmonary surgery. Registration number: ChiCTR2200067120. URL: https://www.chictr.org.cn/
Sex differences in long-term survival after total arterial coronary artery bypass grafting
Authors: Ren Justin , Bowyer Andrea , Tian David H , Reid Christopher M , Hwang Bridget , Royse Colin , El-Ansary Doa , Royse Alistair
Published: March 2024

OBJECTIVES

It is uncertain if the evidence on improved long-term survival of total arterial coronary artery bypass grafting applies to female patients. This study aims to compare the long-term survival outcomes of using total arterial revascularization (TAR) versus at least 1 saphenous vein graft separately for men and women.

METHODS

This retrospective analysis of the Australian and New Zealand Society of Cardiac-Thoracic Surgical Database had administrative linkage to the National Death Index. We identified all patients undergoing primary isolated coronary bypass from June 2001 to January 2020 inclusive. Following sex stratification, propensity score matching with 36 variables and Cox proportional hazard regression were used to facilitate adjusted comparisons. A Cox interaction-term analysis was performed to investigate the impact of sex on TAR survival benefit. The primary outcome was all-cause mortality.

RESULTS

Of the 69 624 eligible patients receiving at least 2 grafts, 13 019 (18.7%) were female patients. Matching generated 14 951 male and 3530 female pairs. Compared to vein-dependent procedures, TAR was associated with significantly reduced incidence of long-term all-cause mortality for both male (hazard ratio, 0.86; 95% confidence interval, 0.81–0.91; P < 0.001) and female (hazard ratio, 0.82; 95% confidence interval, 0.73–0.91; P < 0.001) cohorts. Interaction-term analysis indicated no significant subgroup effect from sex (P = 0.573) on the survival advantage of TAR. The treatment effect provided by TAR remained significant across most sex-stratified disease subgroups.

CONCLUSIONS

TAR, when compared to the use of at least 1 saphenous vein graft, provides comparable superior long-term survival outcomes in both females and males.
Anti-Solutionism and Anti-Formalism in Global Algorithmic Governance Studies
Authors: Mignot-Mahdavi Rebecca
Published: March 2024

Digital and non-digital modes of governing the international legal order co-exist. This imbrication brings with it a particular constellation of actors, new sites and processes of governance and new modalities of law-making. Claudia Aradau and Tobias Blanke, in Algorithmic Reason, guide us through the complex cartographies of global governance. They eloquently map the networks and infrastructures of algorithmic governance and show how they affect the relations between the governing and the governed. Thereby, they help us visualize the imbrication of the local and the global, of private and public infrastructural logics beyond the static binaries that shape our traditional understanding of the international legal order. Throughout multiple case studies, two major transversal claims emerge in the book that are relevant to international lawyers. The book, in my view, argues for (i) an anti-solutionist and (ii) an anti-formalist analysis of global algorithmic governance. As these two transversal claims are not always fully unpacked and explicitly embraced, this review essay aims to draw the contours of these claims, unpack them and show how valuable they can be to think about global algorithmic governance and the functions of international law in the equation.
Reductions in remnant cholesterol and VLDL cholesterol through inhibition of ANGPTL3 protein synthesis: an analysis from the TRANSLATE-TIMI 70 trial
Authors: Zimerman Andre , Wiviott Stephen D , Park Jeong-Gun , Murphy Sabina A , Ran Xinhui , Bramson Candace R , Curto Madelyn , Ramos Vesper , Jevne Alexandra , Kuder Julia F , Verma Subodh , Wojakowski Wojtek , Terra Steven G , Sabatine Marc S , Bergmark Brian A , Marston Nicholas A
Published: March 2024

Aims

Remnant cholesterol and very low-density lipoprotein cholesterol (VLDL-C) are increasingly recognized risk factors for atherosclerotic disease with few therapeutic options. Angiopoietin-like 3 (ANGPTL3), a key protein in the metabolism of triglyceride-rich lipoproteins, is a promising target.

Methods and results

TRANSLATE-TIMI 70 was a double-blind, placebo-controlled randomized trial testing seven dose regimens of vupanorsen, an antisense oligonucleotide against ANGPTL3, in adults with non-HDL-C ≥ 100 mg/dL and triglycerides 150–500 mg/dL. The primary endpoint of this analysis was percentage change in remnant cholesterol (total cholesterol minus directly measured LDL-C minus HDL-C) and VLDL-C (directly measured) over 24 weeks. Two hundred eighty-six patients were enrolled, with a median age of 64 years and 44% female. Median baseline remnant cholesterol and VLDL-C were 42 and 31 mg/dL, respectively (reference: <30 mg/dL). Vupanorsen lowered remnant cholesterol by 42–59% at 24 weeks over placebo (P < 0.001), achieving a median level of 18 mg/dL at the highest dose. Over the same period, VLDL-C was reduced by 52–67% over placebo (P < 0.001), with a median achieved level of 2.5 mg/dL at the highest dose. The effect of vupanorsen on remnant cholesterol and VLDL-C reduction was dose-dependent and directly associated with the degree of ANGPTL3 inhibition: at 90% ANGPTL3 reduction, there was a 61% and 81% decrease in remnant cholesterol and VLDL-C, respectively.

Conclusion

Inhibition of ANGPTL3 protein synthesis significantly lowered remnant cholesterol and VLDL-C in patients with hypertriglyceridaemia. The magnitude of reduction was associated with the degree of ANGPTL3 inhibition. These findings support ANGPTL3 inhibition as a promising target for lowering cholesterol on triglyceride-rich lipoproteins.
Optimal Mating of Pinus taeda L. Under Different Scenarios Using Differential Evolution Algorithm
Authors: Goda Khushi , Isik Fikret
Published: March 2024

A newly developed software, AgMate, was used to perform optimized mating for monoecious Pinus taeda L. breeding. Using a computational optimization procedure called differential evolution, AgMate was applied under different breeding population sizes scenarios (50, 100, 150, 200, and 250) and candidate contribution scenarios (maximum use of each candidate was set to 1 or 8), to assess its efficiency in maximizing the genetic gain while controlling inbreeding. A population of 962 Pinus taeda parents with a known pedigree from the North Carolina State University Tree Improvement Program was used to optimize objective functions accounting for the coancestry of parents and expected genetic gain and inbreeding of the future progeny. AgMate results were compared with those from another widely used mating software called MateSel. For the proposed mating list of 200 progenies, AgMate resulted in an 83.7% increase in genetic gain compared with the candidate population. There was evidence that AgMate performed similarly to MateSel in managing coancestry and expected genetic gain, but MateSel was superior in avoiding inbreeding in proposed mate pairs. The developed algorithm was computationally efficient in maximizing the objective functions and flexible for practical application in monoecious diploid conifer breeding. AgMate, with its open-source software, free-to-modify algorithm and front-end ShinyApp, is a necessary addition for the advancement of conifer breeding.

Study Implications: A dataset from a breeding population of loblolly pine (Pinus taeda L.) was analyzed using an optimal mating software, AgMate (developed by the authors), to optimize the selection, contribution, and mating of candidates simultaneously. The software helps breeders decide on trees to cross and the crossing frequency, such that the trees are unrelated and would result in the best-performing progenies. AgMate is effective in meeting the breeding objectives for monoecious diploid species. The open-source, easy-to-use, and flexible AgMate software, also accessible via a website, is invaluable in helping breeders create optimal matings for future generations, which balances the pursuit of maximizing genetic gain while maintaining genetic diversity.
On FRAND as a Means of Information Access
Authors: Kokoulina Olga
Published: March 2024

FRAND (fair, reasonable and non-discriminatory) is a highly debated acronym that has been scrutinised, expounded and tested in scholarly works, courtrooms, and policy discussions. Initially employed as a remedy means and access tool in sector-specific and standards-setting contexts, FRAND has recently made its way into the emerging EU data governance regime. Given this new position, it is appropriate to examine FRAND critically as a universal access mechanism of the information law domain at large.

Drawing on a narrative of FRAND in SEP licensing, this article reflects on the innate capacity of FRAND to act as a flexible governance instrument. Examining regulatory forces and patterns guiding the interpretation of FRAND, the article presents the interplay of self-governance, national and EU layers of regulation. As shown, the determination of FRAND is firmly grounded on institutional and procedural norms, both in a standardisation context and beyond. The analysis highlights the fact that such a regulatory approach has costs and opportunities. To harness the flexibility of FRAND as a universal information access tool, it is essential to gain more clarity as to the content and goals of FRAND-enabled transactions. It is also critical to ensure that the efficiency of such a regulatory approach does not come at the cost of compromising on the protection afforded by EU fundamental rights and freedoms.
Implementation of the split-beam function to Mills cross multibeam echo sounder for target strength measurements
Authors: Matte Guillaume , Gauthier Tehei , Rousselot Nathan , Guillard Jean , Lamouret Marie , Lerda Olivier , Tallon Benoit , Roux Phillipe , Mosca Frederic
Published: March 2024

Modern challenges in the increasing exploitation of aquatic ecosystems require efficient, reliable, and noninvasive technologies to acquire biomass information on a large scale. For the past 40 years, hydroacoustics has been an essential tool to analyse fish populations and their relationship with the environment. Currently, split-beam echo sounders are standard tools used to reliably and accurately record data in oceans, estuaries, and lakes. To maximize the coverage volume and to increase target detection, and therefore data quality, the use of multi-beam echo sounders is a real asset. We propose here an innovative method for target strength (TS) calculation based on the signal from a reversible Mills cross multi-beam sonar, SeapiX (Exail), which also includes the analytical capability of a split-beam echo sounder. This innovative approach provides new original information when using a multi-beam sonar. The case study in Lake Bourget was based on a comparison of the simultaneous recordings of SeapiX and EK80 (SIMRAD) to prove the validity of this multi split-beam processing, as well as to estimate the in situ TS of fish.
Mortality in women with a history of incarceration in Norway: a 20-year national cohort study
Authors: Svendsen Vegard G , Bukten Anne , Skardhamar Torbjørn , Stavseth Marianne Riksheim
Published: March 2024

Background

Women carry a substantial burden of psychiatric, somatic and lifestyle-related morbidity in the prison context. By describing causes of death and estimating the risk and burden of mortality compared with the general population, this study investigates how mortality operates in this highly marginalized and under-researched population.

Methods

In this registry-based study of all women incarcerated in Norwegian prisons from 2000 to 2019 (N = 11 313), we calculated crude mortality rates, years of lost life and, by using mortality in age-matched women from the general population as a reference, age-standardized mortality ratios and years of lost life rates.

Results

Over a mean follow-up time of 10.7 years, at a median age of 50 years, 9% of the population had died (n = 1005). Most deaths (80%) were premature deaths from an avoidable cause. Drug-induced causes and deaths from major non-communicable diseases (NCDs) were most frequent (both 32%). Compared with women in the general population, women with a history of incarceration were more likely to die from any cause. Trends in annual age-standardized years of lost life rates suggest that the mortality burden associated with major NCDs has gradually replaced drug-induced causes.

Conclusions

Women with a history of incarceration die at a greater rate than their peers and largely from avoidable causes. The profile of causes contributing to the substantial burden of mortality placed on this population has changed over time and has important implications for future efforts to reduce morbidity and the risk of premature death following release from prison.
Patient perspectives on the vital primary care role of community pharmacists in Nova Scotia, Canada: qualitative findings from the PUPPY Study
Authors: Isenor Jennifer E , Renaud Lauren , Mathews Maria , Morrison Bobbi , Murphy Andrea L , Bishop Andrea , Bowles Susan K , Kennie-Kaulbach Natalie , Peddle Sarah , Breton Mylaine , Green Michael E , Marshall Emily G
Published: March 2024

Objectives

Community pharmacists play an important role in primary care access and delivery for all patients, including patients with a family physician or nurse practitioner (“attached”) and patients without a family physician or nurse practitioner (“unattached”). During the COVID-19 pandemic, community pharmacists were accessible care providers for unattached patients and patients who had difficulty accessing their usual primary care providers (“semi-attached”). Before and during the pandemic, pharmacist services expanded in several Canadian provinces. The aim of this qualitative study was to explore patient experiences receiving care from community pharmacists, and their perspectives on the scope of practice of community pharmacists.

Methods

Fifteen patients in Nova Scotia, Canada, were interviewed. Participant narratives pertaining to pharmacist care were analyzed thematically.

Key findings

Attached, “semi-attached,” and unattached patients valued community pharmacists as a cornerstone of care and sought pharmacists for a variety of health services, including triaging and system navigation. Patients spoke positively about expanding the scope of practice for community pharmacists, and better optimization of pharmacists in primary care.

Conclusions

System decision-makers should consider the positive role community pharmacists can play in achieving primary care across the Quintuple Aim (population health, patient and provider experiences, reducing costs, and supporting equity in health).
Empirical antimicrobial prescribing for pyelonephritis in patients discharged from 15 US Emergency Departments: an opportunity for improvement
Authors: Rech Megan A , Faine Brett A , Gross Alan E , Vakkalanka Priyanka , Brown Caitlin S , Harding Stephanie J , Slocum Giles , Zimmerman David , Zepeski Anne , Rewitzer Stacey , Howington Gavin T , Campbell Matt , Dawson Jordan , Treu Cierra N , Nelson Lucas , Jones Mandy , Flack Tara , Porter Blake , Sarangarm Preeyaporn , Mattson Alicia E , Bailey Abby , Kelly Gregory , Talan David A
Published: March 2024

Background

Urinary tract infections (UTIs) are commonly treated in the emergency department (ED), and unfortunately, resistance to first-line agents is increasing.

Objectives

To characterize treatment of pyelonephritis in a nationally representative sample of ED patients and to identify patient- and treatment-specific factors associated with receiving initial inactive antibiotics.

Methods

We conducted a multicentre, observational cohort study utilizing the Emergency Medicine PHARMacotherapy Research NETwork (EMPHARM-NET), comprising 15 geographically diverse US EDs. All patients ≥18 years of age with a diagnosis of pyelonephritis between 2018 and 2020 were included. The primary endpoint was the proportion of patients who received initial inactive empirical antibiotic therapy and to identify predictive factors of inactive antibiotic therapy.

Results

Of the 3714 patients evaluated, 223 had culture-positive pyelonephritis. Median patient age was 50.1 years and patients were mostly female (78.3%). Overall, 40.4% of patients received an IV antibiotic, most commonly ceftriaxone (86.7%). The most frequently prescribed antibiotics were cefalexin (31.8%), ciprofloxacin (14.3%), cefdinir (13.5%) and trimethoprim/sulfamethoxazole (12.6%). Overall, 10.3% of patients received initial inactive therapy. After adjustment in a multivariable analysis, long-acting IV antibiotic was predictive of inactive therapy (OR 0.23, 95% CI 0.07–0.83).

Conclusions

In our prospective, multicentre observational study, we found that only 40.4% of patients with pyelonephritis received empirical IV antibiotics in the ED, contributing to inactive therapy. Receipt of long-acting IV antibiotics was independently associated with a decreased rate of initial inactive therapy. This reinforces guideline recommendations to administer long-acting IV antibiotics empirically in the ED upon suspicion of pyelonephritis.
Calcium trafficking and gastrointestinal physiology following an acute lipopolysaccharide challenge in pigs
Authors: Opgenorth Julie , Mayorga Edith J , Abeyta Megan A , Goetz Brady M , Rodriguez-Jimenez Sonia , Freestone Alyssa D , Stahl Chad H , Baumgard Lance H
Published: March 2024

The influence of systemic immune activation on whole-body calcium (Ca) trafficking and gastrointestinal tract (GIT) physiology is not clear. Thus, the study objectives were to characterize the effects of lipopolysaccharide (LPS) on Ca pools and GIT dynamics to increase understanding of immune-induced hypocalcemia, ileus, and stomach hemorrhaging. Twelve crossbred pigs [44 ± 3 kg body weight (BW)] were randomly assigned to 1 of 2 intramuscular treatments: (1) control (CON; 2 mL saline; n = 6) or (2) LPS (40 µg LPS/kg BW; n = 6). Pigs were housed in metabolism stalls to collect total urine and feces for 6 h after treatment administration, at which point they were euthanized, and various tissues, organs, fluids, and digesta were weighed, and analyzed for Ca content. Data were analyzed with the MIXED procedure in SAS 9.4. Rectal temperature and respiration rate increased in LPS relative to CON pigs (1.4 °C and 32%, respectively; P ≤ 0.05). Inflammatory biomarkers such as circulating alkaline phosphatase, aspartate aminotransferase, and total bilirubin increased in LPS compared with CON pigs whereas albumin decreased (P ≤ 0.02). Plasma glucose and urea nitrogen decreased and increased, respectively, after LPS (43% and 80%, respectively; P < 0.01). Pigs administered LPS had reduced circulating ionized calcium (iCa) compared to CON (15%; P < 0.01). Considering estimations of total blood volume, LPS caused an iCa deficit of 23 mg relative to CON (P < 0.01). Adipose tissue and urine from LPS pigs had reduced Ca compared to CON (39% and 77%, respectively; P ≤ 0.05). There did not appear to be increased Ca efflux into GIT contents and no detectable increases in other organ or tissue Ca concentrations were identified. Thus, while LPS caused hypocalcemia, we were unable to determine where circulating Ca was trafficked. LPS administration markedly altered GIT dynamics including stomach hemorrhaging, diarrhea (increased fecal output and moisture), and reduced small intestine and fecal pH (P ≤ 0.06). Taken together, changes in GIT physiology suggested dyshomeostasis and alimentary pathology. Future research is required to fully elucidate the etiology of immune activation-induced hypocalcemia and GIT pathophysiology.
Genetic parameters for carcass traits of progeny of beef bulls mated to dairy cows
Authors: Keele John W , Foraker Blake A , Boldt Ryan , Kemp Chip , Kuehn Larry A , Woerner Dale R
Published: March 2024

Beef × dairy crossbred cattle (n = 615) were used to evaluate the effect of preharvest indicator traits and genotypes on the accuracy of estimated breeding values (EBVs) of seedstock candidates for selection. Genotypes for 100,000 single nucleotide polymorphisms were provided by the American Simmental Association of purebred and crossbred seedstock animals (n = 2,632). Five hundred and ninety-five of the 615 beef × dairy cattle had carcass camera and ultrasound data. Phenotypes were not used for any of the seedstock animals even though some may have had performance and ultrasound data. We estimated the genomic relationship matrix among 3,247 animals including both phenotyped and unphenotyped animals. We computed genetic parameters among 37 traits using 666 bivariate restricted maximum likelihood analyses. The accuracy of EBV depends on heritability. For the sake of brevity, we report accuracy for marbling as a proxy for other traits with similar heritability. We focus on accuracy for marbling because marbling is the primary determinant of carcass value. We computed EBV for all 3,247 animals for marbling based on camera data postharvest using best linear unbiased prediction. We report evidence of overlap in causative genes among postharvest carcass traits; marbling, ribeye area, yield grade, fat thickness, and hot carcass weight (HCW) based on genetic correlations. Genetic correlations range from −0.73 to 0.89. Several live animal traits (frame size, body weight and ultrasound fat thickness and ribeye area) were genetically correlated with postharvest traits; including HCW, ribeye area, yield grade, fat thickness, and marbling. Genetic correlations between pre- and postharvest traits ranged from −0.53 to 0.95. Accuracy for marbling ranged from 0.64 to 0.80 for animals with marbling recorded, and from 0.09 to 0.60 for animals without marbling recorded. The accuracy of animals without phenotypes was related to the genomic relationship between animals with phenotype and those without. Live animal traits were useful for predicting economically important carcass traits based on genetic correlations. The accuracy of EBV for seedstock animals that were not phenotyped was low, but this is consistent with theory, and accuracy is expected to increase with the addition of genotypes and carcass data from beef × dairy animals.
The Gender Gap in Earnings Losses After Job Displacement
Authors: Illing Hannah , Schmieder Johannes , Trenkle Simon
Published: March 2024

We compare men and women who are displaced from similar jobs by applying an event study design combined with propensity score matching and reweighting to administrative data from Germany. After a mass layoff, women’s earnings losses are about 35% higher than men’s, with the gap persisting 5 years after displacement. This is partly explained by women taking up more part-time employment, but even women’s full-time wage losses are almost 50% higher than men’s. Parenthood magnifies the gender gap sharply. Finally, displaced women spend less time on job search and apply for lower-paid jobs, highlighting the importance of labor supply decisions.
Integrating tertiary lymphoid structure–associated genes into computational models to evaluate prognostication and immune infiltration in pancreatic cancer
Authors: Ma Ying , Li Xuesong , Zhang Jin , Zhao Xiangqin , Lu Yi , Shen Guangcong , Wang Guowen , Liu Hong , Hao Jihui
Published: March 2024

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor response to all therapeutic modalities and dismal prognosis. The presence of tertiary lymphoid structures (TLSs) in various solid cancers is of crucial prognostic significance, highlighting the intricate interplay between the tumor microenvironment and immune cells aggregation. However, the extent to which TLSs and immune status affect PDAC prognosis remains incompletely understood. Here, we sought to unveil the unique properties of TLSs in PDAC by leveraging both single-cell and bulk transcriptomics, culminating in a risk model that predicts clinical outcomes. We used TLS scores based on a 12-gene (CCL2, CCL3, CCL4, CCL5, CCL8, CCL18, CCL19, CCL21, CXCL9, CXCL10, CXCL11, and CXCL13) and 9-gene (PTGDS, RBP5, EIF1AY, CETP, SKAP1, LAT, CCR6, CD1D, and CD79B) signature, respectively, and examined their distribution in cell clusters of single-cell data from PDAC samples. The markers involved in these clusters were selected to develop a prognostic model using The Cancer Genome Atlas Program database as the training cohort and Gene Expression Omnibus database as the validation cohort. Further, we compared the immune infiltration, drug sensitivity, and enriched and differentially expressed genes between the high- and low-risk groups in our model. Therefore, we established a risk model that has significant implications for the prognostic assessment of PADC patients with remarkable differences in immune infiltration and chemosensitivity between the low- and high-risk groups. This paradigm established by TLS-related cell marker genes provides a prognostic prediction and a panel of novel therapeutic targets for exploring potential immunotherapy.
“Multi-Product Critical Loss: Allowing for Varying Margins, Prices, and Quantities in the Candidate Antitrust Market”
Authors: Ulrick Shawn W , Williams Mark D
Published: March 2024

Critical loss analysis is important in defining antitrust product and geographic markets as it directly implements the hypothetical monopolist test. Traditionally, critical loss analysis assumes all products in the candidate market earn the same margin at current prices. In effect, this approach treats all products as a single, representative product. This is technically incorrect. This paper develops the appropriate measures of critical loss assuming products in the candidate markets have different margins, different current prices, and different initial quantities. We also address issues in the implementation of critical loss analysis. This paper is meant to be accessible to the practitioner.
Clinical Performance of Plasma Metagenomic Sequencing in Immunocompromised Pediatric Patients
Authors: Lehman Alice C , Goren Lea R , Evans Michael D , Toles Olivia , Drozdov Daniel , Andrews Shannon L , McAllister Shane C , Thielen Beth K
Published: March 2024

The performance of plasma metagenomic next-generation sequencing was evaluated in an immunocompromised pediatric population. The clinical impact was limited, with management changes in 13% of cases. Moreover, organisms thought to be non-pathogenic were commonly detected. Prospective studies in specific populations are required to clarify the utility of this emerging technology.
Heterogeneous paths to stability
Authors: Di Porto Edoardo , Tealdi Cristina
Published: March 2024

In this paper, we show that incentives to convert temporary contracts into permanent ones might be less effective when the employment protection legislation associated with temporary contracts is lax. Drawing upon rich administrative data and using a difference-in-differences methodology, we estimate that workers at their first work experience hired on more flexible contracts undergo a reduction in the conversion rate to permanent employment of 6.3 percentage points after the implementation of the incentives (and of 3.2 percentage points over a year), compared to peers hired on more rigid contracts. This reduced conversion rate, which results in a 17% wage penalty even 2 years into their professional journey, points to a significant negative impact of flexible temporary jobs on the future prospects of young workers.
Analysis of diurnal variation in serum testosterone levels in men with symptoms of testosterone deficiency
Authors: Novaes Luis F , Flores Jose M , Benfante Nicole , Schofield Elizabeth , Katz Darren J , Nelson Chris J , Mulhall John P
Published: March 2024

Background

Testosterone (T) plays a crucial role in various physiological functions in men, and understanding the variations in T levels during the day is essential for diagnosing and treating testosterone deficiency (TD).

Aim

We sought to evaluate the reduction in serum total T (TT) levels throughout the day in men with symptoms of testosterone deficiency and to determine the variables having an impact on the extent of this decline.

Methods

The study population consisted of a group of men who within 3 months of each other had all undergone both early morning and afternoon TT level measurements. We did not include patients with a history of a prior orchiectomy, testosterone levels below 100 ng/dL or above 1000 ng/dL, a history of androgen deprivation therapy, or patients on T therapy. Statistical analyses were conducted using descriptive statistics, t-tests, chi-square tests, and correlation calculations. Liquid chromatography–tandem mass spectrometry was used to measure TT, and a change in TT levels greater than 100 ng/dL was considered significant. Using multivariable and univariable analysis, we attempted to define predictors of a decrease in afternoon TT levels.

Outcomes

The majority of men showed no significant difference in T levels between morning and afternoon.

Results

In total, 506 men with a median age of 65 years were analyzed. The most common comorbidities were hypertension and hyperlipidemia. Levels of TT were measured in the morning and afternoon, and no significant differences in mean T levels based on the time of the test were found. Age was not significantly associated with T levels.

Clinical Implications

There was a weak negative correlation between age and the difference between morning and afternoon T levels, with younger men showing more significant variations in T levels. The most considerable differences in T levels were observed in men younger than 30 years. There were no predictors of the magnitude of the T decrease in the afternoon.

Strengths and Limitations

Strengths of the study include the number of subjects and the use of liquid chromatography–tandem mass spectrometry for T measurement. Limitations include failure to measure morning and afternoon T levels on the same day, the retrospective nature of the study, and a smaller sample size of patients younger than 30 years.

Conclusion

In this study we found no strong link between age and daily T fluctuation, but we observed a decrease in the magnitude of variation with aging. The group experiencing the most significant decline in daily T had higher morning and consistently normal afternoon T levels.
Histoplasmaantigens as novel players for the development of new enzyme immunoassays for the serodiagnosis of histoplasmosis: A comparative study of their analytical performance
Authors: Rodríguez Laboccetta Carolina , Briceño Fernández Víctor J , Videla Garrido Agustín , Posse Gladys B , Cuestas María L , Nusblat Alejandro D
Published: March 2024

Definitive diagnosis of histoplasmosis relies on culture and/or cytology/histopathology; however, these procedures have limited sensitivity and cultures are time-consuming. Antibodies detection by immunodiffusion has low sensitivity in immunocompromised individuals and uses histoplasmin (HMN), a crude antigenic extract, as reagent. Novel protein antigen candidates have been recently identified and produced by DNA-recombinant techniques to obtain standardized and specific reagents for diagnosing histoplasmosis.

To compare the analytical performance of novel enzyme-linked immunosorbent assays (ELISAs) for antibodies testing for diagnosing histoplasmosis using different Histoplasma capsulatum antigens as reagents.

The H. capsulatum 100 kDa protein (Hcp100), the M antigen and its immunoreactive fragment F1 were produced by DNA-recombinant techniques. Galactomannan was purified from both the yeast and mycelial cell walls (yGM and mGM, respectively). The analytical performance of the ELISA tests for the serological detection of antibodies against these antigens was evaluated and compared with those obtained using HMN as reagent.

Antibodies detection by the Hcp100 ELISA demonstrated 90.0% sensitivity and 92.0% specificity, versus 43.3% sensitivity and 95.0% specificity of the M ELISA, 33.3% sensitivity and 84.0% specificity of the F1 ELISA, 96.7% sensitivity and 94.0% specificity of the yGM ELISA, 83.3% sensitivity and 88.0% specificity of the mGM ELISA, and 70.0% sensitivity and 86.0% specificity for the HMN ELISA.

In summary, Hcp100 is proposed as the most promising candidate for the serodiagnosis of histoplasmosis. The primary immunoreactive element in HMN proved to be GM rather than the M antigen. Nevertheless, a higher incidence of cross-reactions was noted with GM compared to M.
Pre-donation Assessment of Cystatin C to Improve Prediction of Pre- and Post-Donation GFR in Potential Living Kidney Donors
Authors: van der Weijden Jessica , Kremer Daan , Westenberg Lisa B , Sanders Jan-Stephan F , Pol Robert A , Nolte Ilja M , De Borst Martin H , Berger Stefan P , Bakker Stephan J L , van Londen Marco
Published: March 2024

Background and hypothesis

Accurate estimation of glomerular filtration rate (GFR) is crucial in living kidney donation. While most eGFR equations are based on plasma creatinine, its levels are strongly influenced by muscle mass. Application of cystatin C (CysC)-based estimates before donation may improve both estimation of current GFR and prediction of post-donation GFR.

Methods

We assessed the performance of CKD-EPI equations based on creatinine (eGFRcreat-2009, eGFRcreat-2021), cystatin C (eGFRCysC-2012), or both (eGFRcombined-2012, eGFRcombined-2021) for estimating pre- and post-donation measured GFR in 486 living kidney donors. We subsequently focused on a subgroup of individuals with high/low muscle mass (25% highest/lowest 24-hour urinary creatinine excretion, sex-stratified and height-indexed).

Results

Pre-donation eGFRcombined 2012 and eGFRcombined 2021 showed the strongest associations with pre- and post-donation mGFR. Pre-donation eGFRcombined 2021 was most accurate for estimating both pre-donation (bias 0.01±11.9 mL/min/1.73m2) and post-donation mGFR (bias 1.3±8.5 mL/min/1.73 m2). In donors with high/low muscle mass, CysC-based equations (with or without creatinine) performed better compared to equations based on only creatinine.

Conclusions

In conclusion, combined eGFR equations yielded a better estimate of pre- and post-donation mGFR, compared to estimates based on creatinine or CysC only. The added value of CysC seems particularly pronounced in donors with high or low muscle mass.
Sequence-activity mapping via depletion reveals striking mutational tolerance and elucidates functional motifs in Tur1a antimicrobial peptide
Authors: Collins Jonathan , Hackel Benjamin J
Published: March 2024

Proline-rich antimicrobial peptides (PrAMPs) are attractive antibiotic candidates that target gram-negative bacteria ribosomes. We elucidated the sequence-function landscape of 43 000 variants of a recently discovered family member, Tur1a, using the validated SAMP-Dep platform that measures intracellular AMP potency in a high-throughput manner via self-depletion of the cellular host. The platform exhibited high replicate reproducibility (ρ = 0.81) and correlation between synonymous genetic variants (R2 = 0.93). Only two segments within Tur1a exhibited stringent mutational requirements to sustain potency: residues 9YLP11 and 19FP20. This includes the aromatic residue in the hypothesized binding domain but not the PRP domain. Along with unexpected mutational tolerance of PRP, the data contrast hypothesized importance of the 1RRIR4 motif and arginines in general. In addition to mutational tolerance of residue segments with presumed significance, 77% of mutations are functionally neutral. Multimutant performance mainly shows compounding effects from removed combinations of prolines and arginines in addition to the two segments of residues showing individual importance. Several variants identified as active from SAMP-Dep were externally produced and maintained activity when applied to susceptible species exogenously.
Electroencephalographic spectro-spatial covariance patterns related to phenoconversion in isolated rapid eye movement sleep behavior disorder and their longitudinal trajectories in α-synucleinopathies
Authors: Park Kyoungeun , Shin Jung Hwan , Byun Jung-Ick , Jeong El , Kim Han-Joon , Jung Ki-Young
Published: March 2024

Study Objectives

This study aimed to identify electroencephalographic (EEG) spectro-spatial covariance patterns associated with phenoconversion in isolated rapid eye movement sleep behavior disorder (iRBD) patients and explore their longitudinal trajectories within α-synucleinopathies.

Methods

We assessed 47 participants, including 35 patients with iRBD and 12 healthy controls (HC), through baseline eye-closed resting EEGs. Patients with iRBD underwent follow-up EEG assessments and 18 patients with iRBD converted (12 to Parkinson’s disease (PD), 6 to dementia with Lewy bodies [DLB]) during follow-up. We derived EEG spectro-spatial covariance patterns for PD-RBD and DLB-RBD from converters and HC. Correlations with motor and cognitive function, baseline distinctions among iRBD converters and nonconverters, and longitudinal trajectories were examined.

Results

At baseline, converters exhibited higher PD-RBD and DLB-RBD beta2 pattern scores compared to nonconverters (each area under curve [AUC] = 0.7751). The delta and alpha spatial patterns effectively distinguished both PD and DLB converters from HC, with the alpha pattern showing high discriminative power (AUC = 0.9097 for PD-RBD, 0.9306 for DLB-RBD). Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part III scores correlated positively with PD-RBD and DLB-RBD delta patterns (Spearman’s rho = 0.688, p = 0.00014; rho = 0.539, p = 0.0055, respectively), with age and sex as cofactors. Distinct trajectories emerged during follow-up among PD converters, DLB converters, and iRBD nonconverters.

Conclusions

Unique EEG spectro-spatial patterns specific to PD-RBD and DLB-RBD offer potential as predictive markers for phenoconversion to α-synucleinopathies in iRBD.
PA and NP burnout in orthopedic surgery
Authors: Drennen Alexis V. , Heard Jeremy C. , D'Antonio Nicholas D. , Kepler Christopher K.
Published: March 2024

Objective:

To quantify the burnout rate among physician associates/assistants (PAs) and NPs in a large orthopedic surgery practice affiliated with an academic institution.

Methods:

The Maslach Burnout Inventory (MBI) and original research questions were given to all PAs and NPs in orthopedics at the facility. Burnout was defined as a high level of emotional exhaustion or depersonalization on the MBI subscale.

Results:

Of the 129 PAs and NPs in orthopedics at our institution, 91 (70.5%) completed all survey items. Nearly 42% of respondents were burned out, as defined by high depersonalization or emotional exhaustion. PAs and NPs who met the burnout criteria were significantly older than those who did not (41.8 ± 10 versus 36.5 ± 7.71 years, P = .007) and spent longer in practice (12.4 ± 6.66 versus 9.35 ± 6.41 years, P = .01).

Conclusions:

The prevalence of burnout is high among PAs and NPs in orthopedics who practice in an academic setting.
The Efficacy of Low-Titer Group O Whole Blood Compared With Component Therapy in Civilian Trauma Patients: A Meta-Analysis
Authors: Morgan Katrina M. , Abou Khalil Elissa , Feeney Erin V. , Spinella Philip C. , Lucisano Amelia C. , Gaines Barbara A. , Leeper Christine M.
Published: March 2024

OBJECTIVES:

To assess if transfusion with low-titer group O whole blood (LTOWB) is associated with improved early and/or late survival compared with component blood product therapy (CT) in bleeding trauma patients.

DATA SOURCES:

A systematic search of PubMed, CINAHL, and Web of Science was performed from their inception through December 1, 2023. Key terms included injury, hemorrhage, bleeding, blood transfusion, and whole blood.

STUDY SELECTION:

All studies comparing outcomes in injured civilian adults and children who received LTOWB versus CT were included.

DATA EXTRACTION:

Data including author, publication year, sample size, total blood volumes, and clinical outcomes were extracted from each article and reported following the Meta-analysis Of Observational Studies in Epidemiology guidelines. Main outcomes were 24-hour (early) and combined 28-day, 30-day, and in-hospital (late) mortality rates between recipients of LTOWB versus CT, which were pooled using random-effects models.

DATA SYNTHESIS:

Of 1297 studies reviewed, 24 were appropriate for analysis. Total subjects numbered 58,717 of whom 5,164 received LTOWB. Eleven studies included adults-only, seven included both adults and adolescents, and six only included children. The median (interquartile range) age for patients who received LTOWB and CT was 35 years (24–39) and 35.5 years (23–39), respectively. Overall, 14 studies reported early mortality and 22 studies reported late mortality. LTOWB was associated with improved 24-hour survival (risk ratios [RRs] [95% CI] = 1.07 [1.03–1.12]) and late (RR [95% CI] = 1.05 [1.01–1.09]) survival compared with component therapy. There was no evidence of small study bias and all studies were graded as a moderate level of bias.

CONCLUSIONS:

These data suggest hemostatic resuscitation with LTOWB compared with CT improves early and late survival outcomes in bleeding civilian trauma patients. The majority of subjects were injured adults; multicenter randomized controlled studies in injured adults and children are underway to confirm these findings.