bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Recommendations of a Height-Based Dosing Regimen of Tobramycin for Cystic Fibrosis in Adults: A Population Pharmacokinetic Analysis
Authors: Koloskoff Kevin , Thirion Daniel J. G. , Matouk Elias , Marsot Amélie 
Published: September 2022

Background:
Acute pulmonary exacerbations (APEs) in patients with adult cystic fibrosis (CF) are treated with a beta-lactam and an aminoglycoside for activity against Pseudomonas aeruginosa (PA). Emerging drug resistance and changing pharmacokinetic profile in an aging population involve a reevaluation of tobramycin dosing recommendations. The objective of this study was to develop a population pharmacokinetic model and establish optimal dosing recommendations for tobramycin using Monte Carlo simulations.

Methods:
This retrospective clinical study and data collection were performed at the CF center of the McGill University Health Center (MUHC), Canada. Model development and simulations were performed using a nonlinear mixed-effect modeling approach (NONMEM, version 7.4.2). The ratios of maximal concentration (Cmax) to the minimal inhibitory concentration (MIC) (Cmax/MIC ≥8 and ≥10) and area under the curve (AUC) to the MIC (AUC/MIC ≥70 and ≥100) were evaluated.

Results:
Adult patients with CF (n = 51) treated with tobramycin were included in the study. Plasma concentrations of tobramycin were obtained for 699 samples from the MUHC database. The two-compartmental model best described the pharmacokinetics of tobramycin. The association of patient height with the central volume of distribution significantly improved this model. Height, rather than weight, induced the best reduction in objective function. According to simulations, doses between 3.4 mg/cm and 4.4 mg/cm were necessary to achieve Cmax/MIC values of ≥8 and ≥10, respectively. However, higher doses were required to achieve the AUC/MIC targets.

Conclusions:
This study demonstrated that height of the patients seems to be more suitable than their weight for dosing adjustments in adult patients with CF. According to this model, initial doses of tobramycin between 3.4 and 4.4 mg/cm should be recommended for patients with a median height of 164 cm and weight of 55 kg to achieve the target plasma concentrations.
“Should I Tell My Leader or Not?”—Health-Oriented Leadership and Stigma as Antecedents of Employees' Mental Health Information Disclosure Intentions at Work
Authors: Pischel Sarah , Felfe Jörg 
Published: September 2022

ObjectiveTo investigate how health-oriented leadership and stigma facilitate or impede employees' disclosure intentions to leaders.MethodsIn two studies—an experimental vignette (n = 73) and a cross-sectional study (n = 220)—we manipulated or measured health-oriented leadership, transformational leadership, and organizational stigma and compared different reasons for disclosure (mental health problems and severe error) to separate general and specific disclosure decisions.ResultsHealth-oriented leadership fostered disclosure above and beyond transformational leadership. High organizational stigma was associated with lower disclosure. Health-oriented leadership had a stronger effect on disclosing mental problems than on disclosing a severe error and slightly mitigated the negative relationship between stigma and disclosure in study 1. Findings were not influenced by employees' current mental health status.ConclusionsOur findings highlight the importance of health-oriented leadership as a facilitator and organizational stigma as a barrier to disclosure intentions.
The Effect of Shiftwork on Body Composition
Authors: Sooriyaarachchi Piumika , Jayawardena Ranil , Pavey Toby , King Neil A. 
Published: September 2022

Objective
This study compared the body composition parameters between shiftworkers and nonshiftworkers in a hospital setting in Sri Lanka.

Methods
A comparative cross-sectional study was carried out among a sample of 78 health care workers, recruited by a stratified random sampling technique. Subjects underwent anthropometric and bioimpedentiometric analysis for body composition parameters.

Results
The mean (SD) body fat percentage (BF%) of shiftworking women (40.8 [SD, 6.8%]) was significantly higher than day-working women (36.7% [SD, 5.9%]) (P < 0.05). Mean BF% between day and shift groups did not significantly differ (33.0% [SD, 6.9%] vs 32.4% [SD, 10.7%]). Body mass index and waist circumference were significantly higher among shiftworking women (P < 0.05), whereas male workers showed the opposite trend.

Conclusion
Prolonged exposure to shiftwork was associated with a higher BF%. Therefore, interventions for shiftworkers must be addressed, focusing on improving body composition.
Disease Status at Diagnosis in Danish Children with α1‐antitrypsin Deficiency
Authors: Winther Christina Louise , Nyrann Sofie , Nielsen Rasmus Gaardskaer , Duno Morten , Johansen Klaus Birkelund , Helt Thora Wesenberg , Christensen Vibeke Brix 
Published: September 2022

Objectives:The aim of this cross‐sectional study was to assess the state of disease at the time of diagnosis in Danish children with α1‐antitrypsin deficiency as Denmark has a high prevalence of ZZ‐homozygosity.Methods:Children either heterozygous, compound heterozygous, or homozygous for Z‐ and S‐variants in the SERPINA1‐gene were included. Clinical characteristics, SERPINA1‐genotype, and blood serum (S) concentrations were recorded concurrently with genetic testing. Serum liver marker concentrations were compared using T tests and Wilcoxon‐Mann‐Whitney tests. Generalized estimating equation (GEE) linear regression models, both univariable and multivariable adjusted for age and sex, were applied to identify correlations with serum α1‐antitrypsin (S‐AAT). The relationship between S‐AAT concentration and genotype was assessed using logistic regression with GEE.Results:The study included 183 of 225 children genetically tested for alpha‐1‐antitrypsin deficiency (AATD). Of these, 36.6% were homozygous for the Z‐variant. Of the heterozygotes, 89.7% had a ZM genotype and the remaining had either an MS genotype or were compound heterozygous. At diagnosis, ZZ‐homozygous children had higher serum concentrations of liver enzymes and conjugated bilirubin, but lower concentrations of S‐AAT compared with heterozygotes. Serum concentrations of conjugated bilirubin and liver enzymes were negatively associated with S‐AAT. Children under 6 months of age had higher total S‐bilirubin concentrations than children over 6 months of age.Conclusions:A low S‐AAT concentration is a strong indicator of homozygosity, and homozygous children have higher enzymatic and cholestatic parameters compared with heterozygous children at diagnosis. This underlines the importance of measuring the S‐AAT concentration in children with prolonged neonatal jaundice.
Health‐related Quality of Life in a Prospective Study of Ultrasound to Detect Cystic Fibrosis–related Liver Disease in Children
Authors: Schwarzenberg Sarah Jane , Palermo Joseph J. , Ye Wen , Huang Suiyuan , Magee John C. , Alazraki Adina , Freeman A. Jay , Harned Roger , Karmazyn Boaz , Karnsakul Wikrom , Leung Daniel H. , Ling Simon C. , Masand Prakash , Molleston Jean P. , Murray Karen F. , Navarro Oscar M. , Nicholas Jennifer L. , Otto Randolph K. , Paranjape Shruti M. , Siegel Marilyn J. , Stoll Janis , Towbin Alexander J. , Narkewicz Michael R. , Alonso Estella M. ,   CFLD NET, Freeman A. Jay , Romero Rene , Alazraki Adina L. , Karnsakul Wikrom W. , Paranjape Shruti M. , Dunn Emily , Alonso Estella M. , McColley Susanna , Nicholas Jennifer L. , Palermo Joseph J. , Ziady Assem G. , Towbin Alexander J. , Narkewicz Michael R. , Harned Roger K. , Leung Daniel H. , Masand Prakash , Molleston Jean P. , Bozic Molly , Karmazyn Boaz W. , Schwarzenberg Sarah Jane , Seidel Glenn F. , Stoll Janis , Kulkarni Sakil , Siegel Marilyn , Green Nicole , Murray Karen , Otto Randolph K. , Ling Simon C. , Navarro Oscar M. , Magee John C. , Ye Wen , Doo Edward , Sherker Averell H. 
Published: September 2022

Objectives:Cystic fibrosis liver disease (CFLD) begins early in life. Symptoms may be vague, mild, or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health‐Related Quality of Life (HRQOL) in children enrolled in a multi‐center study of CFLD to determine the impact of early CFLD on general and disease‐specific QOL.Methods:Ultrasound (US) patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child‐reported (age ≥5 years) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire‐revised (CFQ‐R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1 year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling‐Lawley trace tested for differences among US groups.Results:Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ‐R at baseline. Parents of NOD reported no change in PedsQL/CFQ‐R over the next year. Child‐report PedsQL/CFQ‐R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ‐R scores related to weight.Conclusions:Early undiagnosed or pre‐symptomatic liver disease had no impact on generic or disease‐specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement.
Magnetic Resonance Imaging to Assess Body Composition Change in Adolescents With Obesity After Sleeve Gastrectomy
Authors: Berg Elizabeth A. , Huang Zixing , Wang Youya , Woo Baidal Jennifer , Fennoy Ilene , Lavine Joel E. , Zitsman Jeffrey , Shen Wei 
Published: September 2022

Objectives:
Metabolic and bariatric surgery is the most effective weight loss treatment for severe obesity. The number of adolescents undergoing sleeve gastrectomy is increasing. We investigated changes in body composition in adolescents undergoing sleeve gastrectomy 12–26 weeks post-operatively using whole-body magnetic resonance imaging (WB-MRI).

Methods:
This prospective cohort study assessed changes in adipose tissue compartments (ie, visceral, subcutaneous, and intermuscular) and muscle in 18 obese adolescents, ages 14–19, 89% female, with body mass index z-score of 2.6 ± 0.25 (range 2.16–3.2). All underwent WB-MRI 1.5–17 weeks pre-operatively and 12–26 weeks post-operatively.

Results:
Pre- and post-operative WB-MRI showed decreases in all adipose tissue compartments, as well as decreased skeletal muscle and liver fat fraction (P < 0.0001). The post-operative percentage loss of adipose tissue in subcutaneous, visceral, and intermuscular compartments (89.0%, 5.8%, 5.2%, respectively) was similar to the pre-operative percentages of corresponding adipose tissue compartments (90.5%, 5.0%, 4.5%, respectively). Of note, participants with obstructive sleep apnea had significantly higher pre-operative volume of subcutaneous and intermuscular adipose tissue than participants without obstructive sleep apnea (P = 0.003).

Conclusions:
We found, contrary to what is reported to occur in adults, that pre-operative percentage loss of adipose tissue in subcutaneous, visceral, and intermuscular compartments was similar to the post-operative percentage loss of corresponding adipose tissue compartments in adolescents 12–26 weeks after sleeve gastrectomy.
Analysis of Cross-sectional and Longitudinal HLA and Anti-viral Responses After COVID Infection in Renal Allograft Recipients: Differences and Correlates
Authors: Girnita Alin L. , Wang Lin , Colovai Adriana I. , Ahearn Patrick , Azzi Yorg , Menon Madhav C. , Fernandez-Vina Marcelo , Gebel Howard M. , Steve Woodle E. , Cravedi Paolo , Maltzman Jonathan S. , Akalin Enver 
Published: September 2022

Background.
Characterization of anti-HLA versus anti-severe acute respiratory syndrome coronavirus 2 (anti–SARS-CoV-2) immune globulin isotypes in organ transplant recipients after coronavirus disease 2019 (COVID-19) infection has not been reported. We aimed to determine changes in anti-HLA antibodies in renal transplant patients with COVID-19 and compare the immunoglobulin and epitope-binding pattern versus anti–SARS-CoV-2 antibodies.

Methods.
This is a cross-sectional study of 46 kidney transplant recipients including 21 with longitudinal sampling. Using a semi-quantitative multiplex assay, we determined immunoglobulin (Ig) M, IgA, IgG, and IgG1-2-3-4 antibodies against Class I and Class II HLA, and 5 SARS-CoV-2 epitopes including the nucleocapsid protein and multiple regions of the spike protein.

Results.
Fourteen of 46 (30%) patients had donor-specific anti-HLA antibodies (donor-specific antibody [DSA]), 12 (26%) had non-DSA anti-HLA antibodies and 45 (98%) had anti–SARS-CoV-2 antibodies. Most DSAs targeted HLA-DQ (71%), with a dominant IgG isotype and IgG1 subtype prevalence (93%), and/or IgG3 (64%), followed by IgG2 (36%). Comparatively, there was a higher prevalence of IgA (85% versus 14%, P = 0.0001) and IgM (87%, versus 36%, P = 0.001) in the anti–SARS-CoV-2 antibody profile, when compared to DSAs, respectively. Anti–SARS-CoV-2 antibody profile was characterized by increased prevalence of IgM and IgA, when compared to DSAs. The median calculated panel reactive antibody before COVID-19 diagnosis (24%) tended to decrease after COVID-19 diagnosis (10%) but it was not statistically significant (P = 0.1).

Conclusions.
Anti-HLA antibody strength and calculated panel reactive antibody in kidney transplant recipients after COVID-19 do not significantly increase after infection. Although the IgG isotype was the dominant form in both HLA and SARS-CoV-2 antigens, the alloimmune response had a low IgA pattern, whereas anti–SARS-CoV-2 antibodies were high IgA/IgM.
Altered visual cortex excitability in premenstrual dysphoric disorder: evidence from magnetoencephalographic gamma oscillations and perceptual suppression
Authors: Manyukhina Viktoriya O. , Orekhova Elena V. , Prokofyev Andrey O. , Obukhova Tatiana S. , Stroganova Tatiana A. 
Published: September 2022

AbstractPremenstrual dysphoric disorder (PMDD) is a psychiatric condition characterized by extreme mood shifts, anxiety, and irritability during the premenstrual period. Abnormal sensitivity to allopregnanolone, a neurosteroid that normally potentiates inhibition, and an increased ratio of neural excitation-to-inhibition (E/I) have been linked to the pathophysiology of PMDD. We hypothesized that in subjects with PMDD these factors will lead to an altered frequency of magnetoencephalographic (MEG) visual gamma oscillations, altered modulation of their power by the strength of excitatory drive and to an altered perceptual spatial suppression.We examined women with PMDD and age-matched control women twice: during the asymptomatic follicular and symptomatic luteal phases of the menstrual cycle (MC). MEG gamma oscillations were recorded while modulating excitatory drive to the visual cortex by increasing drift rate of high-contrast visual grating. Visual perceptual suppression was assessed as the degree of deterioration of motion direction discrimination with increasing stimulus size.In women with PMDD, the peak frequency of the gamma response (GR) and its modulation by the drift rate were normal, whereas modulation of the GR power was significantly altered. A moderate increase in drift rate had an unusually strong facilitating effect on the GR power in PMDD, regardless of the MC phase. In contrast, the normally suppressive effect of a strong increase in drift rate was attenuated in PMDD during the luteal phase and predicted symptom severity assessed on the same day. Perceptual spatial suppression did not differ between the groups, but decreased from the follicular to the luteal phase only in PMDD subjects.The atypical GR power modulation suggests that neuronal excitability in the visual cortex is constitutively elevated in women with PMDD, and that this E/I imbalance is further exacerbated during the luteal phase, possibly due to an abnormal sensitivity to neurosteroids. However, the unchanged frequency of GR and normal spatial suppression in women with PMDD speak against the dysfunction of their inhibitory neurons, at least those involved in generation of visual gamma oscillations.Three key pointsAtypical modulation of visual gamma power by excitatory drive in women with PMDD suggests the presence of neuronal hyperexcitability, which is exacerbated during the symptomatic luteal phase, possibly due to altered sensitivity to neurosteroids.The peak frequency of gamma oscillations does not differ between women with PMDD and control women and demonstrates the luteal phase-specific effect of the 1st scan in both groups, which suggest normal functioning of inhibitory neurons in the visual cortex in PMDD.The presence of normal perceptual spatial suppression also speaks against inhibitory deficit in the visual cortex in PMDD.
Adaptive and neutral processes that select on life course diversification
Authors: Steiner Ulrich , Tuljapurkar Shripad 
Published: September 2022

AbstractHeterogeneity among individuals in fitness components is what selection acts upon. One of the fundamental questions in evolution is how such heterogeneity arises and is maintained. Fundamental evolutionary theories predict that selection acts against such heterogeneity but contrasting these predictions substantial non-genetic and non-environmental driven variability in phenotypes can be observed; not only under highly controlled lab conditions, but also in less controlled settings. Here we ask, by analysing structured population models across a large range of biological taxa, how selective forces act on the processes that generate variation among life courses. Our findings suggest that non-genetic, non-environmental driven variation is in general neither truly neutral, selected for, or selected against. Much variation exists among species and populations within species, with mean patterns suggesting close to neutral evolution of life course variability. Populations that show greater diversity of life courses do not show, in general, increased or decreased population growth rates, and selective forces acting on the processes of diversification seem not to generally increase or decrease life course variability. Approaches in quantitative genetics that identified similar lack of understanding of maintenance of variability might be extended to include non-genetic and non-environmental driven variability. We believe to be only at the beginning in understanding the evolution and maintenance of non-genetic non environmental variation.
Equilibrium policy portfolios when some investors are restricted from holding certain assets
Authors: Randl Otto , Westerkamp Arne , Zechner Josef 
Published: September 2022

PurposeThe authors analyze the equilibrium effects of non-tradable assets on optimal policy portfolios. They study how the existence of non-tradable assets impacts optimal asset allocation decisions of investors who own such assets and of investors who do not have access to non-tradable assets.Design/methodology/approachIn this theoretical analysis, the authors analyze a model with tradable and non-tradable asset classes whose cash flows are jointly normally distributed. There are two types of investors, with and without access to non-tradable assets. All investors have constant absolute risk aversion preferences. The authors derive closed form solutions for optimal investor demand and equilibrium asset prices. They calibrated the model usingUS datafor listed equity, bonds and private equity. Further, the authors illustrate the sensitivities of quantities and prices with respect to the main parameters.FindingsThe study finds that the existence of non-tradable assets has a large impact on optimal asset allocation. Investors with (without) access to non-tradable assets tilt their portfolios of tradable assets away from (toward) assets to which non-tradable assets exhibit positive betas.Practical implicationsThe model provides important insights not only for investors holding non-tradable assets such as private equity but also for investors who do not have access to non-tradable assets. Investors who ignore the effect of non-tradable assets when reverse-engineering risk premia from asset covariances and market capitalizations might severely underestimate the equity risk premium.Originality/valueThe authors provide the first comprehensive analysis of the equilibrium effects of non-tradability of some assets on optimal policy portfolios. Thus, this paper goes beyond analyzing the effects of market imperfections on individual portfolio choices.
Digital literacy skills among African library and information science professionals – an exploratory study
Authors: A. Subaveerapandiyan , Sinha Priyanka , Ugwulebo Jeremiah Emeka 
Published: September 2022

Purpose
This study aims to assess the digital literacy of African library and information science (LIS) professionals. Digital literacy skills are required in the digital library environment.

Design/methodology/approach
Relevant literature was reviewed on this topic; previous study questionnaires, various university LIS curriculum, content analysis and job advertising were used for preparing the survey questionnaire. This study used an ex post facto research design. Purposive sampling was adopted in this study, and data were collected from Google form by sharing the research questionnaire by hyperlink which was undertaken from March 15, 2022 to May 24, 2022. The data were collected by a structured questionnaire. A four-point Likert scale was used to measure how library professionals acquired digital literacy skills. Content analysis of more than 500 job vacancies over the past three years (2018–2022) of library job advertisements was taken randomly.

Findings
This study’s findings show that the majority of the good at basic level of digital literacy skills at the same time have less in advanced digital literacy skills. The finding of this study shows the majority of them have to upgrade and learn about advanced digital literacy skills.

Practical implications
This study recommends adopting a new syllabus and updating a LIS curriculum based on the library’s technological development. Furthermore, this study’s potential result suggests more practical classes instead of theoretical study and it is useful to the library schools, associations, MOOC providers and lifelong learners.

Originality/value
This study is conducted with 102 African library professionals from 13 countries. This study discusses futuristic digital literacy skills and basic literacy skills. This study is beneficial to those who are preparing a new curriculum in LIS fields.