bluuebunny/crossref_metadata_2025_split huggingface dataset:
α1‐Acid Glycoprotein Concentrations and Cerebrospinal Fluid Drug Distribution after Subarachnoid Hemorrhage
Authors: Woodward Donald K. , Hatton Jimmi , Ensom Mary H. H. , Young Byron , Dempsey Robert , Clifton G. Dennis 
Published: October 2023

Study Objective. To test the hypothesis that changes in α1‐acid glycoprotein (AAG) concentration alter central nervous system (CNS) drug distribution after subarachnoid hemorrhage.Design. Two‐phase, prospective study.Setting. University‐associated medical center.Patients. Twenty‐one patients with subarachnoid hemorrhage.Intervention. In phase I, serum AAG concentrations of patients with subarachnoid hemorrhage were measured serially and compared with those in 21 controls undergoing elective neurosurgical procedures. In phase II, nimodipine was the pharmacologic probe to determine the relationship between drug distribution into the CNS and changes in AAG concentration.Measurements and Main Results. Serum and cerebrospinal fluid (CSF) samples were collected from patients with subarachnoid hemorrhage treated with nimodipine and used to measure total and unbound drug concentrations. Concentrations of AAG were 39% higher in patients than in controls preoperatively. They decreased significantly by 24 hours after surgery in patients and increased in controls. In both groups the concentrations were higher than reported normal values. During the period of reduced AAG concentration, calculated unbound nimodipine concentrations were 3‐fold higher (p<0.05) than at later periods, with a trend toward higher total concentrations. Overall, mean CSF nimodipine concentration was 6.4% of mean serum total concentration. The CSF concentrations decreased as AAG concentrations increased, independent of serum concentrations (r = −0.52, p<0.02).Conclusion. Concentrations of AAG change after subarachnoid hemorrhage and are transiently influenced by surgery. Unbound drug concentration increases when AAG concentrations decrease, whereas CSF concentrations decrease when AAG concentrations increase. These preliminary findings suggest that changes in AAG concentrations can alter unbound serum nimodipine concentrations and may affect CSF drug distribution.
Optimal Management of Amiodarone Therapy: Efficacy and Side Effects
Authors: Hilleman Daniel , Miller Mary Ann , Parker Robert , Doering Paul , Pieper John A. 
Published: October 2023

Objectives. To review management and dosing guidelines for amiodarone therapy, and discuss the drug's adverse event profile.Methods. Review of relevant studies and reports.Results. Amiodarone is a highly effective antiarrhythmic drug, but is associated with adverse effects involving several organs. Amiodarone‐induced arrhythmia is rare, with frequency of 0.3% in one study. Pulmonary toxicity is the most serious noncardiac side effect (2–17% of patients). Hypersensitivity pneumonitis can appear early in the course of therapy. Interstitial pneumonitis is a more common but insidious pulmonary reaction characterized by cough, low‐grade fever, and dyspnea that occurs after months or years of therapy. Clinically important hypothyroidism and hyperthyroidism occur in 2–10% of patients. Optic neuritis or neuropathy in which patients experience decreased or blurred vision may progress to permanent blindness. Abnormalities in liver function tests, especially elevated aminotransferase and alkaline phosphatase levels, are seen in 4–25% of patients. Neurologic side effects were reported in 20–40% of patients, at times associated with tremor, ataxia, peripheral neuropathy, malaise or fatigue, sleep disturbances, dizziness, and headaches. Several types of dermatologic reactions have been reported, including allergic rash, photosensitivity, and blue‐gray skin discoloration. The best strategy for early detection of pulmonary toxicity is vigilant clinical follow‐up with monitoring of cardiac status and liver and thyroid function, and prescription of the lowest effective dosage. After an initial loading dose, 200 mg/day in many patients maintains arrhythmia control and minimizes the frequency of side effects.Conclusion. Amiodarone is a safe and efficacious antiarrhythmic agent when lower dosages are given to patients who are closely monitored and subject to careful follow‐up.
A Novel Approach: A Guide to Using Literature and Film in the Classroom
Authors: Iancu Martha A. 
Published: October 2023

Being There: Elisabeth Gareis, Martine S. Allard, Susan Gill, and Jacqueline J. Saindon Pp. vi + 110 (Student Workbook) Pp. vi + 62 (Teacher's Manual) Ann Arbor: University of Michigan Press, 1997.Fried Green Tomatoes: Elisabeth Gareis, Martine S. Allard, Susan Gill, and Jacqueline J. Saindon Pp. viii + 83 (Student Workbook) Pp. vi + 85 (Teacher's Manual) Ann Arbor: University of Michigan Press, 1998.The Shawshank Redemption: Elisabeth Gareis, Martine S. Allard, and Jacqueline J. Saindon Pp. vi + 98 (Student Workbook) Pp. vi + 106 (Teacher's Manual)
The inter‐laboratory validation study of EpiSensA for predicting skin sensitization potential
Authors: Mizumachi Hideyuki , Watanabe Mika , Ikezumi Mayu , Kajiwara Michika , Yasuda Michiyo , Mizuno Makoto , Imai Noriyasu , Sakuma Megumi , Shibata Momoko , Watanabe Shin‐ichi , Motoyama Junko , Basketter David , Eskes Chantra , Hoffmann Sebastian , Lehmann David M. , Ashikaga Takao , Sozu Takashi , Takeyoshi Masahiro , Suzuki Sho , Miyazawa Masaaki , Kojima Hajime 
Published: October 2023

AbstractThe Epidermal Sensitization Assay (EpiSensA) is a reconstructed human epidermis (RhE)‐based gene expression assay for predicting the skin sensitization potential of chemicals. Since the RhE model is covered by a stratified stratum corneum, various kinds of test chemicals, including lipophilic ones and pre‐/pro‐haptens, can be tested with a route of exposure akin to an in vivo assay and human exposure. This article presents the results of a formally managed validation study of the EpiSensA that was carried out by three participating laboratories. The purpose of this validation study was to assess transferability of the EpiSensA to new laboratories along with its within‐ (WLR) and between‐laboratory reproducibility (BLR). The validation study was organized into two independent stages. As demonstrated during the first stage, where three sensitizers and one non‐sensitizer were correctly predicted by all participating laboratories, the EpiSensA was successfully transferred to all three participating laboratories. For Phase I of the second stage, each participating laboratory performed three experiments with an identical set of 15 coded test chemicals resulting in WLR of 93.3%, 93.3%, and 86.7%, respectively. Furthermore, when the results from the 15 test chemicals were combined with those of the additional 12 chemicals tested in Phase II of the second stage, the BLR for 27 test chemicals was 88.9%. Moreover, the predictive capacity among the three laboratories showed 92.6% sensitivity, 63.0% specificity, 82.7% accuracy, and 77.8% balanced accuracy based on murine local lymph node assay (LLNA) results. Overall, this validation study concluded that EpiSensA is easily transferable and sufficiently robust for assessing the skin sensitization potential of chemicals.
Gastric inhibitory polypeptide receptor antagonism suppresses intramuscular adipose tissue accumulation and ameliorates sarcopenia
Authors: Takahashi Yuya , Fujita Hiroki , Seino Yusuke , Hattori Satoko , Hidaka Shihomi , Miyakawa Tsuyoshi , Suzuki Atsushi , Waki Hironori , Yabe Daisuke , Seino Yutaka , Yamada Yuichiro 
Published: October 2023

AbstractBackgroundIntramuscular adipose tissue (IMAT) formation derived from muscle fibro‐adipogenic progenitors (FAPs) has been recognized as a pathological feature of sarcopenia. This study aimed to explore whether genetic and pharmacological gastric inhibitory polypeptide (GIP) receptor antagonism suppresses IMAT accumulation and ameliorates sarcopenia in mice.MethodsWhole body composition, grip strength, skeletal muscle weight, tibialis anterior (TA) muscle fibre cross‐sectional area (CSA) and TA muscle IMAT area were measured in young and aged male C57BL/6 strain GIP receptor (Gipr)‐knockout (Gipr−/−) and wild‐type (Gipr+/+) mice. FAPs isolated from lower limb muscles of 12‐week‐old Gipr+/+ mice were cultured with GIP, and their differentiation into mature adipocytes was examined. Furthermore, TA muscle IMAT area and fibre CSA were measured in untreated Gipr−/− mice and GIP receptor antagonist‐treated Gipr+/+ mice after glycerol injection into the TA muscles.ResultsBody composition analysis revealed that 104‐week‐old Gipr−/− mice had a greater proportion of lean tissue mass (73.7 ± 1.2% vs. 66.5 ± 2.7%, P < 0.05 vs. 104‐week‐old Gipr+/+ mice) and less adipose tissue mass (13.1 ± 1.3% vs. 19.4 ± 2.6%, P < 0.05 vs. 104‐week‐old Gipr+/+ mice). Eighty‐four‐week‐old Gipr−/− mice exhibited increases in grip strength (P < 0.05), weights of TA (P < 0.05), soleus (P < 0.01), gastrocnemius (P < 0.05) and quadriceps femoris (P < 0.01) muscles, and average TA muscle fibre CSA (P < 0.05) along with a reduction in TA muscle IMAT area assessed by the number of perilipin‐positive cells (P < 0.0001) compared with 84‐week‐old Gipr+/+ mice. Oil Red O staining analysis revealed 1.6‐ and 1.7‐fold increased adipogenesis in muscle FAPs cultured with 10 and 100 nM of GIP (P < 0.01 and P < 0.001 vs. 0 nM of GIP, respectively). Furthermore, both untreated Gipr−/− mice and GIP receptor antagonist‐treated Gipr+/+ mice for 14 days after glycerol injection into the TA muscles at 12 weeks of age showed reduced TA muscle IMAT area (1.39 ± 0.38% and 2.65 ± 0.36% vs. 6.54 ± 1.30%, P < 0.001 and P < 0.01 vs. untreated Gipr+/+ mice, respectively) and increased average TA muscle fibre CSA (P < 0.01 and P < 0.05 vs. untreated Gipr+/+ mice, respectively).ConclusionsGIP promotes the differentiation of muscle FAPs into adipocytes and its receptor antagonism suppresses IMAT accumulation and promotes muscle regeneration. Pharmacological GIP receptor antagonism may serve as a novel therapeutic approach for sarcopenia.
Mammalian target of rapamycin inhibition impacts energy homeostasis and induces sex‐specific body weight loss in humans
Authors: Mannaa Marwan , Pfennigwerth Pia , Fielitz Jens , Gollasch Maik , Boschmann Michael 
Published: October 2023

AbstractBackgroundPrevious data from a 2‐year randomized controlled trial (CRAD001ADE12) indicated that mammalian target of rapamycin (mTOR) inhibition by everolimus slowed cyst growth in patients with autosomal‐dominant polycystic kidney disease (ADPKD). During the trial, we noted body weight loss in some patients, particularly in women. We hypothesized that everolimus causes body weight reduction by reduced food intake and/or metabolic changes, which could lead to cachexia.MethodsWithin a sub‐analysis of the CRAD001ADE12 trial, body weight course was investigated regarding sex‐specific differences in 433 adult ADPKD patients (everolimus, n = 215; placebo, n = 218). One hundred four out of 111 patients who participated in the clinical trial centre in Berlin were evaluated under everolimus/placebo therapy (on drug: everolimus, n = 48; placebo, n = 56) and after therapy (off drug: everolimus, n = 15; placebo, n = 18). Eating habits and nutrient/caloric intake were evaluated by validated questionnaires. Systemic and local metabolism was evaluated in four patients after an oral glucose load (OGL) by using calorimetry and adipose/muscle tissue microdialysis.ResultsWithin the 2‐year CRAD001ADE12 trial, a significant body weight loss was observed in female patients on everolimus versus placebo (P = 0.0029). Data of the Berlin Cohort revealed that weight loss was greater in women on everolimus versus men (P < 0.01). After 9 months, women and men had lost 2.6 ± 3.8 and 0.8 ± 1.5 kg (P < 0.05) in body weight, respectively, and after 21 months, they had lost 4.1 ± 6.6 and 1.0 ± 3.3 kg (P < 0.05), respectively. On everolimus, caloric intake was significantly lower in women versus men (1510 ± 128 vs. 2264 ± 216 kcal/day, P < 0.05), caused mainly by a lower fat and protein intake in women versus men. Cognitive restraints, disinhibition and hunger remained unchanged. In a subgroup of patients resting metabolic rate was unchanged whereas OGL‐induced thermogenesis was reduced (7 ± 2 vs. 11 ± 2 kcal, P < 0.05). Fasting and OGL‐induced fat oxidation was increased (P < 0.05) on versus off everolimus. In adipose tissue, fasting lipolytic activity was increased, but lipolytic activity was inhibited similarly after the OGL on versus off everolimus, respectively. In skeletal muscle, postprandial glucose uptake and aerobic glycolysis was reduced in patients on everolimus.ConclusionsmTOR inhibition by everolimus induces body weight reduction, specifically in female patients. This effect is possibly caused by a centrally mediated reduced food (fat and protein) intake and by centrally/peripherally mediated increased fat oxidation (systemic) and mobilization (adipose tissue). Glucose uptake and oxidation might be reduced in skeletal muscle. This could lead to cachexia and, possibly, muscle wasting. Therefore, our results have important implications for patients recieving immune‐suppressive mTOR inhibition therapy.
Anorexia of aging: An international assessment of healthcare providers' knowledge and practice gaps
Authors: Aprahamian Ivan , Coats Andrew J. , Morley John E. , Klompenhouwer Tatiana , Anker Stefan D. ,   the International Advisory Board, and Regional Advisory Boards for North America, Latin America, Europe and Japan
Published: October 2023

AbstractBackgroundAnorexia of aging is a common geriatric syndrome that includes loss of appetite and/or reduced food intake, with associated undernutrition, unintended weight loss, sarcopenia, functional decline, loss of independence and other adverse health outcomes. Anorexia of aging can have multiple and severe consequences and is often overlooked by healthcare professionals (HCPs). Even more concerningly, clinicians commonly accept anorexia of aging as an inevitable part of ‘normal’ aging. The aim of this assessment was to identify current gaps in professional knowledge and practice in identifying and managing older persons with anorexia. Results may guide educational programmes to fill the gaps identified and therefore improve patient outcomes.MethodsThis international assessment was conducted using a mixed‐methods approach, including focus group interviews with subject matter experts and an electronic survey of practicing HCPs. The assessment was led by the Society on Sarcopenia, Cachexia and Wasting Disorders (SCWD) and was supported by in‐country collaborating organizations.ResultsA quantitative survey of 26 multiple‐choice questions was completed by physicians, dietitians and other HCPs (n = 1545). Most HCPs (56.8%) recognize a consistent definition of anorexia of aging as a loss of appetite and/or low food intake. Cognitive changes/dementia (91%) and dysphagia (87%) are seen as the biggest risk factors. Most respondents were confident to give nutritional (62%) and physical activity (59.4%) recommendations and engaged caregivers such as family members in supporting older adults with anorexia (80.6%). Most clinicians assessed appetite at each visit (66.7%), although weight is not measured at every visit (41.5%). Apart from the Mini‐Nutritional Assessment Short Form (39%), other tools to screen for appetite loss are not frequently used or no tools are used at all (29.4%). A high number of respondents (38.7%) believe that anorexia is a normal part of aging. Results show that treatment is focused on swallowing disorders (78%), dentition issues (76%) and increasing oral intake (fortified foods [75%] and oral nutritional supplements [74%]). Nevertheless, the lack of high‐quality evidence is perceived as a barrier to optimal treatment (49.2%).ConclusionsFindings from this international assessment highlight the challenges in the care of older adults with or at risk for anorexia of aging. Identifying professional practice gaps between individual HCPs and team‐based gaps can provide a basis for healthcare education that is addressed at root causes, targeted to specific audiences and developed to improve individual and team practices that contribute to improving patient outcomes.
Comparing findings from the random‐intercept cross‐lagged panel model and the monozygotic twin difference cross‐lagged panel model: Maladaptive parenting and offspring emotional and behavioural problems
Authors: Kullberg Marie‐Louise J. , Van Schie Charlotte C. , Allegrini Andrea G. , Ahmadzadeh Yasmin , Wechsler Daniel L. , Elzinga Bernet M. , McAdams Tom A. 
Published: October 2023

AbstractBackgroundIn this study we compare results obtained when applying the monozygotic twin difference cross‐lagged panel model (MZD‐CLPM) and a random intercept cross‐lagged panel model (RI‐CLPM) to the same data. Each of these models is designed to strengthen researchers' ability to draw causal inference from cross‐lagged associations. We explore differences and similarities in how each model does this, and in the results each model produces. Specifically, we examine associations between maladaptive parenting and child emotional and behavioural problems in identical twins aged 9, 12 and 16.MethodChild reports of 5698 identical twins from the Twins Early Development Study (TEDS) were analysed. We ran a regular CLPM to anchor our findings within the current literature, then applied the MZD‐CLPM and the RI‐CLPM.ResultsThe RI‐CLPM and MZD‐CLPM each enable researchers to evaluate the direction of effects between correlated variables, after accounting for unmeasured sources of potential confounding. Our interpretation of these models therefore focusses primarily on the magnitude and significance of cross‐lagged associations. In both the MZD‐CLPM and the RI‐CLPM behavioural problems at age 9 resulted in higher levels of maladaptive parenting at age 12. Other effects were not consistently significant across the two models, although the majority of estimates pointed in the same direction.ConclusionIn light of the triangulated methods, differences in the results obtained using the MZD‐CLPM and the RI‐CLPM underline the importance of careful consideration of what sources of unmeasured confounding different models control for and that nuance is required when interpreting findings using such models. We provide an overview of what the CLPM, RI‐CLPM and MZD‐CLPM can and cannot control for in this respect and the conclusions that can be drawn from each model.
Time‐series analyses and cohort studies to investigate relationships between particulate matter and mortality—two approaches to one endpoint
Authors: Englert Norbert 
Published: October 2023

AbstractTime‐series analyses and cohort studies provide different methods of looking at the health effects of air pollution. With respect to mortality, the relative risk associated with a defined increase in the concentration of particulate matter is numerically much higher if derived from cohort studies than if based on time‐series analyses. This discrepancy is often explained by arguing that chronic effects of air pollutants can only be assessed in cohort studies. However, with respect to changes in life expectancy, the results of the two study types can be shown to be consistent. In calculations of pollution‐related health costs, mortality plays a dominant role. Applying the relative risk derived from cohort studies directly as a multiplier on daily or annual mortality leads to a considerable overestimation of effects. Copyright © 1999 John Wiley & Sons, Ltd.
Genetic and environmental effects on processing productivity and food product yield: drudgery of women's work
Authors: Bello Abolore , Agbona Afolabi , Olaosebikan Olamide , Edughaen Gospel , Dufour Dominique , Bouniol Alexandre , Iluebbey Peter , Ndjouenkeu Robert , Rabbi Ismail , Teeken Béla 
Published: October 2023

AbstractBACKGROUNDCassava processing is a crucial source of livelihood for rural farmers and processors in Nigeria and Cameroon. This study investigated the varietal effect on the processing productivity of women farmer processors within their working environment and compared this with the food product quality as evaluated by the processors and the field yield. Field trials were established in Nigeria (Benue and Osun state) and Cameroon (Littoral region). Eight cassava genotypes were evaluated. These eight varieties included newly bred genotypes, commercial checks and varieties provided and preferred by the processors. The roots of these genotypes were harvested and processed intogariandebaby processors. The time of each processing step was recorded. Processors assessed the quality of the roots and food products using pairwise ranking.RESULTSIn the field trials in Cameroon and Nigeria (Benue state), the newly bred genotypes showed superior performance in terms of dry matter content and fresh and dry yield. During processing, genotypes showed significant variation for most assessed parameters in both countries. Some newly bred varieties exhibited lower productivity that can make them more prone to drudgery than the local commercial checks and the varieties provided and preferred by the processors. Newly bred varieties were mostly ranked higher or equal to processors' preferred varieties concerning fresh root and food product quality. In the Cameroon location there were significant varietal differences in processing productivity and drudgery index which suggest that the particular processing methods there ‐ such as pressing methods and fermentation time ‐ cause these varietal differences to matter more.CONCLUSIONSThe varieties that were tested were observed to differ in yield, product quality, processing productivity, and potential drudgery levels. Some breeders' germplasms displayed a combination of increased yields and good product quality and good processor productivity. Those varieties that showed low processor productivity should be avoided during selection to avoid increased labour burden and associated drudgery of women processors. Further research is recommended to enhance food product color, latent culinary qualities, and processing productivity of newly bred varieties to improve acceptability and reduce processing drudgery for women. © 2023 The Authors.Journal of The Science of Food and Agriculturepublished by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.