bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of depression: Are psychotropic drugs appropriately dosed in women and in the elderly? Dosages of psychotropic drugs by sex and age in routine clinical practice
Authors: Greil Waldemar , de Bardeci Mateo , Seifert Johanna , Bernegger Xueqiong , Cattapan Katja , Stassen Hans , Wagner Anita L. , Sieberer Marcel , Grohmann Renate , Toto Sermin 
Published: August 2021

AbstractBackgroundSeveral researchers have shown higher concentration‐dose ratios of psychotropic drugs in women and the elderly. Therefore, lower dosages of psychotropic drugs may be recommended in women and the elderly. This study describes sex‐ and age‐related dosage of psychotropic drugs prescribed to patients with major depressive disorder (MDD) in routine clinical practice.MethodInfluence of sex and age on dosages are analysed for the 10 most commonly prescribed drugs in our dataset consisting of 32,082 inpatients with MDD. Data stems from the European drug safety program “Arzneimittelsicherheit in der Psychiatrie”. The observed sex and age differences in prescriptions are compared to differences described in literature on age‐ and gender‐related pharmacokinetics.ResultsAmong patients over 65 years, a statistically significant decrease in dosages with increasing age (between 0.65% and 2.83% for each increasing year of age) was observed, except for zopiclone. However, only slight or no influence of sex‐related adjustment of dosage in prescriptions was found.ConclusionAge appears to influence adjustment of dosage in most psychotropic drugs, but to a lower extent than data on age‐related pharmacokinetics suggests. Although literature also suggests that lower dosages of psychotropic drugs may be appropriate for females, this study found women are usually prescribed the same dosage as men.
Global View of Per Capita Daily Vitamin D Supply Estimates as Proxy Measures for Vitamin D Intake Data
Authors: Cashman Kevin D. 
Published: August 2021

ABSTRACTNationally representative data on vitamin D intake can inform on the adequacy of dietary supply of vitamin D in a population, but such data is lacking for a majority of countries. Estimates of average per capita supply of vitamin D, as calculated using information from the Food and Agriculture Organisation of the United Nations (FAO) national food balance sheets (FBSs) can be used as proxy measures for vitamin D intake within a population. In the present work, FAO national FBSs (from 2004 to 2017) for 173 to 178 countries around the globe were used to generate such average per capita vitamin D supply estimates. For countries where food fortification with vitamin D was common, the estimates accounted for this. Using the 2004–2013 FBS data, there was a large range in average per capita vitamin D supply ranging from 0.3 (Ethiopia) to 17.8 (Maldives) μg/d. Globally, 40, 60, 70, four, two, and two countries had average per capita vitamin D supply estimates <1.5, 1.6–3, 3.1–5.5, 5.6–7.5, 7.6–10, and >10 μg/d, respectively. Pelagic fish was the major contributory food commodity (supplying 53%–86%) in countries with supply >7.6 μg/d. Median per capita vitamin D supply estimates for constituent countries within Africa, Americas, Asia, Europe, and Oceania were 1.4, 2.7, 2.8, 4.1, and 4.7 μg/d, respectively. These overall supply trends were mirrored in the newer, 2014–2017 FBS data. Fortification of milk and dairy or wheat flour with vitamin D had an important impact on the vitamin D supply estimates (average increments of 1.6 and 3.1 μg/d, respectively). Overall, the work showed how the per capita daily vitamin D supply estimates, as surrogate for vitamin D intake data, can highlight countries where inadequacy of supply may be of concern. It also shows how fortification of food with vitamin D can have an important impact on addressing low vitamin D intake. © 2021 The Author. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PTH and FGF23 Exert Interdependent Effects on Renal Phosphate Handling: Evidence From Patients With Hypoparathyroidism and Hyperphosphatemic Familial Tumoral Calcinosis Treated With Synthetic Human PTH 1–34
Authors: Ovejero Diana , Hartley Iris R , de Castro Diaz Luis Fernandez , Theng Elizabeth , Li Xiaobai , Gafni Rachel I , Collins Michael T 
Published: August 2021

ABSTRACT
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) both influence blood phosphate levels by regulating urinary phosphate reabsorption. Clinical data suggest that adequate renal phosphate handling requires the presence of both FGF23 and PTH, but robust evidence is lacking. To investigate whether the phosphaturic effects of PTH and FGF23 are interdependent, 11 patients with hypoparathyroidism, which features high blood phosphate in spite of concomitant FGF23 elevation, and 1 patient with hyperphosphatemic familial tumoral calcinosis (HFTC), characterized by deficient intact FGF23 action and resulting hyperphosphatemia, were treated with synthetic human PTH 1–34 (hPTH 1–34). Biochemical parameters, including blood phosphate, calcium, intact FGF23 (iFGF23), nephrogenic cAMP, 1,25(OH)2 vitamin D (1,25D), and tubular reabsorption of phosphate (TRP), were measured at baseline and after hPTH 1–34 treatment. In patients with hypoparathyroidism, administration of hPTH 1–34 increased nephrogenic cAMP, which resulted in serum phosphate normalization followed by a significant decrease in iFGF23. TRP initially decreased and returned to baseline. In the patient with HFTC, hPTH 1–34 administration also increased nephrogenic cAMP, but this did not produce changes in phosphate or TRP. No changes in calcium were observed in any of the studied patients, although prolonged hPTH 1–34 treatment did induce supraphysiologic 1,25D levels in the patient with HFTC. Our results indicate that PTH and FGF23 effects on phosphate regulation are interdependent and both are required to adequately regulate renal phosphate handling. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.
The current knowledge concerning solid cancer and therapy
Authors: Najafi Masoud , Majidpoor Jamal , Toolee Heidar , Mortezaee Keywan 
Published: August 2021

AbstractSolid cancers comprise a large number of new cases and deaths from cancer each year globally. There are a number of strategies for addressing tumors raised from solid organs including surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, combinational therapy, and stem cell and extracellular vesicle (EV) therapy. Surgery, radiotherapy, and chemotherapy are the dominant cures, but are not always effective, in which even in a localized tumor there is a possibility of tumor relapse after surgical resection. Over half of the cancer patients will receive radiotherapy as a part of their therapeutic schedule. Radiotherapy can cause an abscopal response for boosting the activity of the immune system outside the local field of radiation, but it may also cause an unwanted bystander effect, predisposing nonradiated cells into carcinogenesis. In the context of immunotherapy, immune checkpoint inhibition is known as the standard‐of‐care, but the major concern is in regard with cold cancers that show low responses to such therapy. Stem‐cell therapy can be used to send prodrugs toward the tumor area; this strategy, however, has its own predicaments, such as unwanted attraction toward the other sites including healthy tissues and its instability. A substitute to such therapy and quite a novel strategy is to use EVs, by virtue of their stability and potential to cross biological barriers and long‐term storage of contents. Combination therapy is the current focus. Despite advances in the field, there are still unmet concerns in the area of effective cancer therapy, raising challenges and opportunities for future investigations.
Neuroprotective effect of α‐pinene self‐emulsifying nanoformulation against 6‐OHDA induced neurotoxicity on human SH‐SY5Y cells and its in vivo validation for anti‐Parkinson's effect
Authors: Srivastava Rajnish , Choudhury Pratim K. , Dev Suresh K. , Rathore Vaibhav 
Published: August 2021

AbstractsOxidative stress (OS) is involved in the multifaceted pathogenic paradigm of neurodegenerative diseases like Parkinson's disease (PD). Monoterpenes like α‐pinene (ALP) is considered to be a therapeutically potent antioxidant agent able to attenuate and scavenge various reactive oxygen species and reactive nitrogen species. The present study aimed to evaluate the in vitro and in vivo neuroprotective effect of α‐pinene self‐emulsifying nanoformulation (ALP‐SENF) for PD. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay was done to evaluate the neurotoxic dose of the ALP‐SENF; however, the neuroprotective effect was assessed by 6‐hydroxydopamine (6‐OHDA) induced neurotoxicity model on SH‐SY5Y taking NAC (N‐acetyl‐l‐cysteine) as standard. The in vivo anti‐Parkinson's activity of the ALP‐SENF was compared with that of the plain ALP suspension by using reserpine antagonism and haloperidol‐induced Parkinsonism model in rats. Various behavioral tests and biochemical antioxidant enzymes were estimated. The in vitro results revealed that treatment with ALP‐SENF at a concentration of 100 and 200 µM was found to show significant neuronal SH‐SY5Y cell viability against 50 µM 6‐OHDA. ALP‐SENF treated animals have seen significant neurobehavioral improvement. Furthermore, the levels of antioxidative enzymes in biochemical test reveals a marked enhancement in the expression of antioxidant enzymes that significantly attenuated the OS induced neurodegeneration. Due to the mechanisms of their antioxidant action, it was probably due to the scavenging of free radicals and the expression of antioxidant enzymes. It also improved neurobehavioral changes induced by reserpine and haloperidol.
Doxazosin and erlotinib have anticancer effects in the endometrial cancer cell and important roles in ERα and Wnt/β‐catenin signaling pathways
Authors: Karaca Büşra , Bakır Elçin , Yerer Mükerrem Betül , Cumaoğlu Ahmet , Hamurcu Zuhal , Eken Ayşe 
Published: August 2021

AbstractERα and Wnt/β‐catenin pathways are critical for the progression of most endometrial cancers. We aimed to investigate the cytotoxic and apoptotic effects of tamoxifen and quinazoline derivative drugs of doxazosin and erlotinib, and their roles in ERα and Wnt/β‐catenin signaling pathways in human endometrial cancer RL 95‐2 cell. 3‐(4,5‐Dimethylthiazol‐2yl)−2,5‐diphenyltetrazolium bromide assay and xCELLigence systems were performed to evaluate cytotoxicity. Furthermore, apoptotic induction was tested by Annexin V analysis. Caspase‐3 and ‐9 activity and changes in the mitochondrial membrane potential were evaluated. The level of reactive oxygen species was measured by incubating with dichlorofluorescein diacetate. Protein ratios of p‐ERα/ERα, GSK3β/p‐GSK3β, and p‐β‐catenin/β‐catenin and expression levels of ESR1, EGFR, c‐Myc genes were evaluated to elucidate mechanisms in signaling pathways. We found that the tested drugs showed cytotoxic and apoptotic effects in the cells. Doxazosin significantly reduced ESR1 expression, slightly reduced the p‐β‐catenin/β‐catenin ratio and c‐Myc expression. Erlotinib significantly increased c‐Myc expression while significantly decreasing the p‐β‐catenin/β‐catenin and p‐ERα/ERα ratio, and ESR1 expression. However, we observed that the cells develop resistance to erlotinib over a certain concentration, suggesting that ERα, ESR1, EGFR, and c‐Myc may be a new target for overcoming drug resistance in the treatment of endometrial cancer. We also observed that erlotinib and doxazosin play an important role in the ERα signaling pathway and can act as potent inhibitors of PKA and/or tyrosine kinase in the Wnt/β‐catenin signaling pathway in RL 95‐2 cell. In conclusion, doxazosin and erlotinib may have a possible therapeutic potential in human endometrial cancer.
Elevated pulmonary levels of Axin2 in mice exposed to herbicide 2,4‐D with or without endotoxin
Authors: Kaur Gurvinder , Verma Ramneek , Mukhopadhyay Chandra Shekhar , Sethi Ramsaran 
Published: August 2021

Abstract2,4‐Dichlorophenoxyacetic acid (2,4‐D), a member of the phenoxy family of herbicides is commonly used in agriculture for controlling broadleaf weeds but its uncontrolled and incoherent use has been linked to incidences of lung toxicity. The present study aimed to understand the molecular mechanisms behind the 2,4‐D alone or in combination with endotoxin (lipopolysaccharide [LPS]) induced pulmonary toxicity. Blood and lung samples were collected from Swiss albino mice (n = 48) following chronic exposure to high (37 mg/kg; 1/10th of LD50) and low (18.5 mg/kg; 1/20th of LD50) doses of 2,4‐D alone or in combination with endotoxin (80 µg/animal). Transcriptome analysis revealed Wnt Canonical signaling as one of the top dysregulated pathways in mice lung following exposure to 2,4‐D with and without endotoxin (LPS) co‐exposure. Global view of differentially expressed genes showed increased messenger RNA expression of Axin2 by 0.26, 2.58, 3.14, 2.59, and 2.97 folds following exposure to LPS, high dose alone or in combination with LPS and low dose alone or in combination with LPS, respectively. The microarray data were validated using quantitative polymerase chain reaction and immunohistochemistry. Furthermore, the plasma concentration of Axin2 was elevated in the high dose group as revealed by Sandwich ELISA. The data taken together suggest a role of Axin2 to activate the Canonical Wnt signaling pathway in 2,4‐D and or endotoxin‐induced lung damage in mice.
Perfect and nearly perfect separation dimension of complete and random graphs
Authors: Yuster Raphael 
Published: August 2021

AbstractThe separation dimension of a hypergraph is the smallest natural number for which there is an embedding of into , such that any pair of disjoint edges is separated by some hyperplane normal to one of the axes. The perfect separation dimension further requires that any pair of disjoint edges is separated by the same amount of such (pairwise nonparallel) hyperplanes. While it is known that for any fixed , the separation dimension of any ‐vertex ‐graph is , the perfect separation dimension is much larger. In fact, no polynomial upper‐bound for the perfect separation dimension of ‐uniform hypergraphs is known. In our first result we essentially resolve the case , that is, graphs. We prove that the perfect separation dimension of is linear in , up to a small polylogarithmic factor. In fact, we prove it is at least and at most . Our second result proves that the perfect separation dimension of almost all graphs is also linear in , up to a logarithmic factor. This follows as a special case of a more general result showing that the perfect separation dimension of the random graph is w.h.p. for a wide range of values of , including all constant . Finally, we prove that significantly relaxing perfection to just requiring that any pair of disjoint edges of is separated the same number of times up to a difference of for some absolute constant , still requires the dimension to be . This is perhaps surprising as it is known that if we allow a difference of , then the dimension reduces to .
Applying the nutrient transfer continuum framework to phosphorus and nitrogen losses from livestock farmyards to watercourses
Authors: Vero Sara E. , Doody Donnacha 
Published: August 2021

AbstractFarmyards are commonly conceptualized as point sources of nutrient pollution nested within the wider agricultural landscape. However, within farmyards there are individual sources and delivery pathways, each of which is affected by a range of management practices and infrastructure. Rainfall mobilizes these nutrients, which may then be delivered to a receptor or to the wider drainage network. As such, the nutrient transfer continuum (NTC), which has been established as a framework to understand and mitigate nutrient loss at a landscape scale, can be similarly applied to disentangle the stages of nutrient transfer from farmyards. The NTC differentiates nutrient transfer into source, mobilization, delivery, and impact stages. This differentiation allows targeting of mitigation measures and evaluation of costs and benefits. This review paper applies the NTC template to farmyard nitrogen and phosphorus transport to conceptualize causative factors and to identify mitigation options.
Genetic counseling student rotations in industry: How COVID‐19 magnified the urgency for virtual learning options in diverse training settings
Authors: Arjunan Aishwarya , Sanders Merideth , Chen Anthony , Roscow Breanna , Ray Jessica 
Published: August 2021

AbstractThe COVID‐19 pandemic created unprecedented challenges worldwide that required rapid adaptation and transformation across the entire healthcare system. Graduate medical training programs across all specialties have moved to rapidly adjust to the virtual landscape. This created a unique opportunity for genetic counselors who work in industry and within diagnostic laboratories to develop internship and rotation programs that can be offered virtually to meet the needs of genetic counseling training programs. Myriad Genetics, Inc., was contacted by numerous graduate programs in genetic counseling beginning in March 2020 requesting the opportunity for their students to participate in remote laboratory‐based rotations. As a result of these requests, a working group of genetic counselors across Myriad came together to adapt existing experiences to fully remote formats and develop new remote‐based opportunities for students. We describe our experience of expanding genetic counseling student rotations during the COVID‐19 pandemic with the goal of providing examples of remote learning experiences that may be applicable to other diagnostic laboratory industry‐based rotations for genetic counseling students. In 2020, a total of 59 second‐year genetic counseling students, from 21 different genetic counseling training programs, participated in one of five different virtual experiences. Furthermore, two new rotation experiences were created to increase capacity and highlight diversity of industry roles. Genetic counselors in industry are uniquely positioned to provide both remote training opportunities for genetic counseling students and exposure to the variety of roles that genetic counselors can occupy. Increasing the exposure to these roles is important as the genetic counseling workforce continues to expand and diversify, and it is imperative among all programs to enable access to these opportunities.
Reconstruction of Middle to Late Quaternary sea level using submerged speleothems from the northeastern Yucatán Peninsula
Authors: Steidle Simon D. , Warken Sophie F. , Schorndorf Nils , Förstel Julius , Schröder‐Ritzrau Andrea , Moseley Gina E. , Spötl Christoph , Aviles Jeronimo , Stinnesbeck Wolfgang , Frank Norbert 
Published: August 2021

ABSTRACTWe examined 14 subaerially deposited speleothems retrieved from submerged caves in the northeastern Yucatán Peninsula (Mexico). These speleothems grew during the Middle to Late Quaternary and were dated by 230Th‐U techniques to provide upper depth limits for past sea levels. We report the first relative sea‐level limits for Marine Isotope Stages (MIS) 11 and 6, and present new evidence for sea‐level oscillations during MIS 5 and early MIS 1. For the latter periods, the origin of growth interruptions is evaluated by combining petrographic methods with trace element analyses. The MIS 5c sea‐level highstand probably occurred between 103.94 ± 0.58 ka and 96.82 ± 0.42 ka and must have exceeded ‐10.8 m (relative to present‐day local sea level). The minimum average rate of sea‐level fall over a 9.4 ka‐long period during the MIS 5e/5d transition is calculated from stalagmite and published coral data at 1.74 ± 0.37 m/ka. For the early Holocene, previous discrepancies with respect to a potential multimetre oscillation of local sea level were found to be challenging to reconcile with the existing speleothem data from the area.
Use of mineral element profiling coupled with chemometric analysis to distinguish Zanthoxylum bungeanum cultivars and health risks of potentially toxic elements in pericarps
Authors: Ma Yao , Wang Xiaona , Huang Chen , Tian Mingjing , Wei Anzhi 
Published: August 2021

AbstractBACKGROUNDZanthoxylum bungeanum pericarps (ZBP) are commonly used as food additives and traditional herbal medicines. Several mineral elements are known to have important physiological functions in organisms, whereas others are reported to have toxic effects. We determined levels of macro elements (Mg, S and Ca), essential trace elements (B, Mn, Fe, Cu, Zn, Se and Mo) and toxic elements (Ni, Al, Cr, As, Cd, Hg and Pb) in the pericarps of 19 Z. bungeanum cultivars. Hazard index values and incremental lifetime cancer risks were calculated to express health risks associated with pericarp consumption. Moreover, several chemometric analyses based on the mineral elements were used to distinguish Z. bungeanum cultivars.RESULTSThe concentrations of 17 determined elements in the pericarps were ranked: Ca > Mg > S > Fe > Al > Mn > Zn > B > Cu > Ni > Pb > Cr > Mo > As > Cd > Hg > Se. The elements Zn, Cr and As had the highest variations in their concentrations. Cu, Mn, Se, Zn, Al, As, Cd, Cr, Hg, Ni and Pb posed some non‐cancer risks, while As and Cd posed cancer risks. Mn, Fe, Zn, and Al were chosen as critical element markers for assessing ZBP using chemometric analyses.CONCLUSIONChemometric analyses could highlight mineral concentration differentiation among the 19 cultivars. The Z. bungeanum cultivar Z12 (from Wudu, Gansu) is best for producing ZBP, and cultivar Z18 (Guanling, Guizhou) can be a reference to classify and evaluate ZBP quality. The results provide valuable information for evaluating the potential safety risks of ZBP and contribute to inter‐cultivar discrimination. © 2021 Society of Chemical Industry.
The selective breeding and mutagenesis mechanism of high‐yielding surfactin Bacillus subtilis strains with atmospheric and room temperature plasma
Authors: Xu Haining , Dai Chunhua , Tang Yingxiu , Xu Xueting , Umego Ekene Christopher , He Ronghai , Ma Haile 
Published: August 2021

AbstractBACKGROUNDSurfactin, a good biological surfactant, is derived from the metabolites of microorganisms. However, the ability of natural strains to produce surfactin is low, and so the presented study aimed to use a novel mutagenesis technology to increase their yields.RESULTSAtmospheric and room temperature plasma (ARTP) was used to conduct mutation breeding of Bacillus subtilis CICC 10721, and a mutant strain M45 with a higher surfactin yield of 34.2% and a stable subculture was screened out. From the fermentation kinetics study, it was found that the maximum cell dry weight, maximum growth rate and surfactin synthesis parameters of the mutant strain M45 were all greater than that of the original strain. Scanning electron microscope and laser scanning confocal microscope observations showed that the spore morphology changed after ARTP treating, and the intracellular Ca2+ concentration of the mutant increased. Genome resequencing analysis showed that 66 single nucleotide poymorphism non‐synonymous mutation sites occurred in M45, and the identification results of the fermentation broth extract from M45 showed that it is composed of C12‐C16 surfactin.CONCLUSIONARTP mutagenesis was found to change the morphology of bacteria, membrane permeability and genes related to the synthesis and secretion of surfactin. The present study provides a basis for industrial production of surfactin and an understanding of the mutagenesis mechanism. © 2021 Society of Chemical Industry.