bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self‐assembled nanoprodrugs from reducible dextran‐diethyldithiocarbamate conjugates for robust tumor‐targeted chemotherapy
Authors: Jin Rong , Yang Zhengshi , Sun Jing , Chang Qing , Cai Li , Lin Chao 
Published: August 2022

AbstractThe development of anticancer prodrugs from repurposing approved drugs offers a rich source of potential new medicines for clinical cancer therapy. Herein, a folate‐decorated dextran prodrug (FADP) conjugate based on disulfiram (DSF), a repurposing drug, was designed for tumor‐targeted chemotherapy. The FADP conjugates with a high drug content (>10%) were readily achieved by the disulfide conjugation between orthopyridyl disulfide dextran (5, 10, and 20 kDa) and diethyldithiocarbamate (DDTC) as the metabolite of DSF. Data showed that the FADP conjugates could self‐assemble to form nanosized prodrugs (nanoprodrugs) with neutral surface charge under physiological conditions and that the nanoprodrugs could actively release DDTC in an intracellular reductive environment. In vitro experiments indicated that the FADP conjugates had a low cytotoxicity in CT‐26 cells but yielded marked cytotoxicity in the presence of copper (II) ions. Moreover, the FADP with 10 kDa of dextran (FADP10k) exerted the best anticancer ability in the cells with comparable anticancer efficacy to that of DSF. The significant anticancer ability of the FADP10k was associated with their folate receptor‐mediated uptake in the cells, following by a high cellular uptake level in comparison with the parent dextran prodrug (DP) without folates. The chemotherapy of the CT‐26 tumor xenografted in Balb/c mouse model elicited that the FADP10k group exerted marked tumor growth inhibition with a minor systemic toxicity at DDTC dose of 20 mg Kg−1 and the anticancer efficacy was superior to that obtained by the DP and DSF groups. This work highlights a high potential of DSF‐based dextran prodrugs for cancer chemotherapy.
Fast fabrication of a light‐scattering polycarbonate with high transmittance, high haze, and excellent flame‐retardant performance
Authors: Duan Yuhao , Yi Ping , Ding Yitong , Li Bowen , Xiong Ying , Guo Shaoyun 
Published: August 2022

AbstractThis paper used a simple, economical, and environmentally benign melt blending process to prepare light‐scattering polycarbonate (PC) containing flame‐retardant scatterers poly(styrene‐co‐acrylonitrile) (SAN)‐hydroxyl‐grafted methylphenylsilicone resin (PSi). During processing, the strong hydrogen bond interaction between PSi and SAN enabled the in‐situ formation of flame‐retardant scatterers SAN‐PSi. With the increase of PSi content, the flame‐retardant properties of PC/SAN‐PSi were greatly improved. After adding 12% PSi, the limit oxygen index (LOI) of the composites increased from 19.0% to 28.0%. The peak heat release rate (pk‐HRR) dropped from 334.3 W g−1 to 213.4 W g−1 and the total heat release rate (Total HR) reduced from 21.7 kJ g−1 to 19.9 kJ g−1, while the transmittance and haze of the composites remained above 88% and 90% respectively, indicating PC/SAN‐PSi was excellent in both light‐scattering and flame‐retardant ability. In short, this work provides an efficient and environment‐friendly fabrication to prepare the light‐scattering PC with excellent flame‐retardant performance, which is expected to be applied to LED and other optoelectronic fields.
Ready to spar: Winning the hearts and minds of college students in the psychoanalytic classroom
Authors: Klein Michael C. 
Published: August 2022

AbstractTeaching psychoanalytic principles to undergraduates is a rewarding and daunting task. Due to societal biases and current academic trends, students arrive with a variety of implicit fears and wishes with respect to the course content. Syllabus development is a unique challenge because there are no standardized foundational concepts. Course requirements, most notably written assignments, are another facet of course development that each instructor chooses to suit their individual goals. This essay is based on 3 years of teaching a senior seminar on psychoanalysis. Data on 39 student course evaluations is described, analyzed, and discussed. Qualitative and quantitative data on student interest, preferences, and satisfaction are included to support the author's recommendations for student learning and engagement.
Simultaneous determination and pharmacokinetic study of six components in beagle dog plasma by UPLC–MS/MS after oral administration of Astragalus Membranaceus aqueous extract
Authors: Yu Xin , Xia Kexin , Wu Siyang , Wang Qiutao , Cheng Wenhao , Ji Chun , Yang Wei , Kang Chen , Yuan Zheng , Li Yingfei 
Published: August 2022

AbstractAstragalus Membranaceus (AM) is widely applied in Chinese herbal compound formulas for treating various kinds of diseases. However, relative pharmacokinetics data on AM in nonrodents is still lacking. Here, an UPLC–MS/MS method for determining the six main compounds of AM was developed. The chromatographic separation was carried out by a Waters Acquity UPLC HSS T3 column (100 × 2.1 mm, 1.8 μm) with gradient elution of water–formic acid (99.98:0.02, v/v) and acetonitrile–formic acid (99.98:0.02, v/v) at a flow rate of 0.3 ml/min within 11 min. Analyses of all compounds were conducted in multiple reaction monitoring mode with a positive/negative ion‐switching mode of an electrospray ionization source in a single run. The analytical method was validated in terms of specificity, linearity, accuracy, precision, stability, etc. The method showed excellent linearity (r > 0.999) over certain concentration ranges. The intra‐day and inter‐day precisions were evaluated, and the RSD values were <12.4%. Furthermore, the validated method was successfully applied to determine the six components in plasma after oral administration of AM aqueous extract to beagle dogs and the pharmacokinetic parameters were obtained. Together, this study provides a reference for medication in the clinical practice of AM.
Arsenic compounds activate MAPK and inhibit Akt pathways to induce apoptosis in MA‐10 mouse Leydig tumor cells
Authors: Juan Wei‐Sheng , Mu Yi‐Fen , Wang Chia‐Yih , So Edmund‐Cheung , Lee Yi‐Ping , Lin Sheng‐Che , Huang Bu‐Miin 
Published: August 2022

AbstractArsenic compounds have been applied treating acute promyelocytic 1eukemia and solid tumors with brief mechanism investigations. In fact, we have demonstrated that sodium arsenite plus dimethylarsenic acid could activate apoptosis in MA‐10 mouse Leydig tumor cells by inducing caspase pathways. However, detail underlying mechanisms how caspase cascade is regulated remains elusive. Therefore, the apoptotic mechanism of sodium arsenite plus dimethylarsenic acid were examined in MA‐10 cells in this study. Our results reveal that Fas/FasL protein expressions were stimulated by sodium arsenite plus dimethylarsenic acid in MA‐10 cells. In addition, reactive oxygen species (ROS) generation, cytochrome C release, Bid truncation, and Bax translocation were induced in MA‐10 cells by arsenic compounds. Moreover, activation of p38, JNK and ERK1/2, MAPK pathways was stimulated while Akt phosphorylated levels and Akt expression were decreased by sodium arsenite plus dimethylarsenic in MA‐10 cells. In conclusion, sodium arsenite and dimethylarsenic acid did activate MAPK pathway plus ROS generation, but suppress Akt pathway, to modulate caspase pathway and then induce MA‐10 cell apoptosis.
Strong founder effect for BRCA1 c.3629_3630delAG pathogenic variant in Chechen patients with breast or ovarian cancer
Authors: Sokolenko Anna P. , Sultanova Luisa V. , Stepanov Ilya A. , Romanko Alexandr A. , Venina Aigul R. , Sokolova Tatiana N. , Musayeva Hedi S. , Tovgereeva Marina Ya. , Magomedova Mareta Kh. , Akhmatkhanov Khusein U. , Vagapova Elisa I. , Suleymanov Elkhan A. , Vasilyeva Elena V. , Bakaeva Elvina Kh. , Bizin Ilya V. , Aleksakhina Svetlana N. , Imyanitov Evgeny N. 
Published: August 2022

AbstractCoding sequences of BRCA1, BRCA2, ATM, TP53, and PALB2 genes were analyzed in 68 consecutive Chechen patients with high‐grade serous ovarian cancer (HGSOC). Pathogenic BRCA1/2 variants were identified in 15 (22%) out of 68 HGSOC cases. Nine out of ten patients with BRCA1 pathogenic alleles carried the same deletion (c.3629_3630delAG), and three out of five BRCA2 heterozygotes had Q3299X allele. The analysis of 49 consecutive patients with triple‐negative breast cancer (TNBC) revealed 3 (6%) additional BRCA1 heterozygotes. All women with BRCA1 c.3629_3630delAG allele also carried linked c.1067G>A (Q356R) single nucleotide polymorphism, indicating that this is a genuine founder variant but not a mutational hotspot. An ATM truncating allele was detected in one HGSOC patient. There were no women with TP53 or PALB2 germline alterations. Genetic analysis of non‐selected HGSOC patients is an efficient tool for the identification of ethnicity‐specific BRCA1/2 pathogenic variants.
Midfacial development and the wisdom of teeth: A case series
Authors: Singh G. Dave , Lee Sangmin 
Published: August 2022

AbstractThe alignment of third molars has largely been overlooked by orthodontists. Since difficulties arise during their eruption, a plethora of surgical procedures is advocated for their management, including prophylactic extraction. This case series describes the use of midfacial development in 4 patients and illustrates successful patterns of third molar eruption.
Bioequivalence of Two Linezolid Tablets Under Fed and Fasting Conditions in Healthy Chinese Individuals
Authors: Wang Shumin , Guo Shaojie , Han Ying , Ni Siyang , Wu Feng , Dai Yuyang , Xia Qiang , Yang Yan , Zhao Xiuli 
Published: August 2022

AbstractLinezolid, an oxazolidinone antibacterial agent with several formulations, has been widely used for over 20 years. This study aimed to compare the bioequivalence, pharmacokinetics, and safety of test and reference linezolid tablets after a single oral dose under fasting/fed conditions. In this open‐label, randomized, two‐period, crossover, bioequivalence study, 48 healthy volunteers were enrolled equally to fasting or fed groups to receive one 600‐mg test or reference linezolid tablet in each period. Pharmacokinetic parameters were calculated using noncompartmental methods. Adverse events (AEs) were recorded to assess safety. The geometric mean terminal half‐lives of test and reference formulations were 3.8 and 3.6 hours, respectively, under both fasting and fed conditions. The median time to reach the maximum observed concentration was 1.0 hour (both formulations) in the fasting group, and 2.0 hours (test formulation) and 2.5 hours (reference formulation) in the fed group. No substantial differences were observed in the area under plasma concentration–time curve (AUC) from time 0 to the last sampling time (AUC0‐t) and the maximum observed concentration (Cmax) between formulations. Geometric least square mean ratios for Cmax, AUC0‐t, and AUC from time 0 to infinity were approximately 100%, and the corresponding 90% confidence intervals for bioequivalence were within 80%–125%. Ten participants reported 11 AEs; AEs were mild, except for one pregnancy event with an outcome of induced absorption. Bioequivalence between the two linezolid formulations was demonstrated under fasting and fed conditions, and a similar safety profile was observed among healthy Chinese volunteers.
A case of multiple solitary neurofibromas located in the hypopharynx and cervical esophagus
Authors: Kazu Hamada , Yuzo Shimode , Yoshiyuki Hata , Hiroaki Kunou , Rika Kobayashi , Kazuhiro Matsunaga , Ken Kawaura , Tsuyoshi Mukai , Hidekazu Kitakata , Tohru Itoh , Masashi Okuro , Sohsuke Yamada 
Published: August 2022

AbstractA 50‐year‐old female was admitted to our hospital because of mild throat discomfort. Esophagogastroduodenoscopy demonstrated multiple 2–3 mm diameter whitish granules in her hypopharynx and cervical esophagus. Based on biopsy specimens, we considered the lesions to represent normal tissue or very mild mucosal dysplasia. However, S‐100 immunohistochemical staining 3 years later led to a diagnosis of multiple solitary neurofibromas located in the hypopharynx and cervical esophagus. Histological finding characteristics of neurofibroma were present in 72.7% of hypopharyngeal biopsy specimens and 33.3% of esophageal specimens. When diagnosing neurofibroma, it is important to perform biopsies at multiple locations and at different times and to enlist the cooperation of endoscopists and pathologists for immunohistochemical staining with S‐100.
Maternal stress and mental health before pregnancy and offspring diurnal cortisol in early childhood
Authors: Guardino Christine M. , Rahal Danny , Rinne Gabrielle R. , Mahrer Nicole E. , Davis Elysia Poggi , Adam Emma K. , Shalowitz Madeleine. U. , Ramey Sharon L. , Schetter Christine Dunkel 
Published: August 2022

AbstractThe current study investigates whether prepregnancy maternal posttraumatic stress disorder (PTSD) symptoms, depressive symptoms, and stress predict children's cortisol diurnal slopes and cortisol awakening responses (CARs) adjusting for relevant variables. Mothers were enrolled after delivering a baby and followed through their subsequent pregnancy with 5 years of longitudinal data on their subsequent child. This prospective design allowed assessment of PTSD symptoms, depressive symptoms, and perceived stress prior to pregnancy. Children provided three saliva samples per day on three consecutive days at two timepoints in early childhood (M age = 3.7 years, SD = 0.38; M age = 5.04 years, SD = 0.43). Mothers’ PTSD symptoms prior to pregnancy were significantly associated with flatter child diurnal cortisol slopes at 4 and 5 years, but not with child CAR. Findings at the age of 4 years, but not 5 years, remained statistically significant after adjustment for maternal socioeconomic status, race/ethnicity, child age, and other covariates. In contrast, maternal prepregnancy depressive symptoms and perceived stress did not significantly predict cortisol slopes or CAR. Results suggest that maternal prepregnancy PTSD symptoms may contribute to variation in early childhood physiology. This study extends earlier work demonstrating risk of adverse outcomes among children whose mothers experienced trauma but associations cannot be disentangled from effects of prenatal mental health of mothers on children's early childhood.
Addressing recent challenges in isotope ratio mass spectrometry: Development of a method applicable to 1‐androstene‐steroids, 6α‐hydroxy‐androstenedione, and androstatrienedione
Authors: Piper Thomas , Thevis Mario 
Published: August 2022

AbstractIn 2020, the confirmation of the non‐endogenous origin of several pseudo‐endogenous steroids by means of isotope ratio mass spectrometry (IRMS) was recommended by the World Anti‐Doping Agency (WADA), in addition to previously established target analytes for IRMS in sports drug testing. To date, however, IRMS‐based methods validated in accordance with current WADA regulations have not been available. Therefore, the aim of this research project was the development and validation of a method to determine the carbon isotope ratios (CIR) of all newly considered pseudo‐endogenous steroids, encompassing the anabolic androgenic steroids comprising a 1‐ene‐core structure (5α‐androst‐1‐ene‐3β,17β‐diol, 5α‐androst‐1‐ene‐3,17‐dione [1AD], 17β‐hydroxy‐5α‐androst‐1‐en‐3‐one, 3α‐hydroxy‐5α‐androst‐1‐ene‐17‐one [1AND], and 3β‐hydroxy‐5α‐androst‐1‐ene‐17‐one [1EpiAND]), as well as steroids referred to as hormone and metabolic modulators (androsta‐1,4,6‐triene‐3,17‐dione [TRD] and its main metabolite 17β‐hydroxy‐androsta‐1,4,6‐triene‐3‐one) and 6α‐ and 6β‐hydroxy‐androst‐4‐ene‐3,17‐dione. With peak purity of target analytes being critical for IRMS analyses, a twofold high‐performance liquid chromatography (HPLC)‐based sample purification was employed, with all analytes being acetylated between the first and second HPLC fractionation. Using established gas chromatography/combustion/IRMS instrumentation, limits of quantification were estimated at 10 ng/ml for a 20 ml urine aliquot for all analytes, except for 1AND (20 ng/ml), and combined measurement uncertainties were estimated between 0.4‰ and 0.9‰. For proof‐of‐concept, samples collected after the single oral administration of a nutritional supplement containing 1AD and 1EpiAND were analyzed as well as existing excretion study urine samples obtained after the administration of 4‐androstenedione and TRD. Based on the obtained results, the developed method was considered to be fit‐for‐purpose.
Cellular basis of differential endochondral growth in Lake Malawi cichlids
Authors: Johnson Savannah , Heubel Brian , Bredesen Carson , Schilling Thomas , Le Pabic Pierre 
Published: August 2022

AbstractBackgroundThe shape and size of skeletal elements is determined by embryonic patterning mechanisms as well as localized growth and remodeling during post‐embryonic development. Differential growth between endochondral growth plates underlies many aspects of morphological diversity in tetrapods but has not been investigated in ray‐finned fishes. We examined endochondral growth rates in the craniofacial skeletons of two cichlid species from Lake Malawi that acquire species‐specific morphological differences during postembryonic development and quantified cellular mechanisms underlying differential growth both within and between species.ResultsCichlid endochondral growth rates vary greatly (50%‐60%) between different growth zones within a species, between different stages for the same growth zone, and between homologous growth zones in different species. Differences in cell proliferation and/or cell enlargement underlie much of this differential growth, albeit in different proportions. Strikingly, differences in extracellular matrix production do not correlate with growth rate differences.ConclusionsDifferential endochondral growth drives many aspects of craniofacial morphological diversity in cichlids. Cellular proliferation and enlargement, but not extracellular matrix deposition, underlie this differential growth and this appears conserved in Osteichthyes. Cell enlargement is observed in some but not all cichlid growth zones and the degree to which it occurs resembles slower growing mammalian growth plates.
Validation study on the child, adult, and parent version of the ARFID module 2.0 for the Eating Disorder Examination
Authors: Schmidt Ricarda , Hiemisch Andreas , Kiess Wieland , von Klitzing Kai , Schlensog‐Schuster Franziska , Hilbert Anja 
Published: August 2022

AbstractObjectiveThis study presents a psychometric evaluation of the avoidant/restrictive food intake disorder (ARFID) module 2.0 for the Eating Disorder Examination (EDE), its child (ChEDE), and parent version. Within a pediatric sample seeking treatment for restrictive feeding or eating disorders and non‐treatment‐seeking controls, the module's interrater reliability, parent–child agreement, and its convergent, divergent, and discriminant validity were examined.MethodThe child, adult, and/or parent version of the German ARFID module was administered to N = 176 children and adolescents (0–17 years) and their parents, as were the (Ch)EDE, well‐established measures on food‐avoidance behaviors, food variety, and body esteem, and objective anthropometric measures.ResultsAcross all versions of the ARFID module, substantial to almost perfect interrater reliability was shown. Parent–child agreement for ARFID diagnosis was substantial. Based on medium‐to‐large associations between interview‐assessed avoidant/restrictive food intake and questionnaire‐assessed food‐avoidance behaviors, food variety, and objective weight status, the module showed high convergent validity, especially for the child and parent version. Low associations of avoidant/restrictive food intake with weight and shape concern demonstrated divergent validity. Individuals with ARFID differed significantly from those with anorexia nervosa and individually matched controls in a range of clinical characteristics, indicating discriminant validity.DiscussionThis comprehensive validation supports the EDE ARFID module to be a valuable measure for the assessment and diagnosis of ARFID in 0–17‐year‐olds based on self‐ and parent‐report. Validation of the ARFID module against other interview‐based measures on ARFID and its evaluation in an adult sample are pending.Public SignificanceBased on good reliability and validity of the avoidant/restrictive food intake disorder (ARFID) module for the Eating Disorder Examination (EDE) in its child, adult, and parent version, the present study paves the way for the clinical and research use of the interview‐based EDE ARFID module for assessing ARFID across childhood and adolescence.
Frequency of hereditary transthyretin amyloidosis among elderly patients with transthyretin cardiomyopathy
Authors: Maestro‐Benedicto Alba , Vela Paula , de Frutos Fernando , Mora Nerea , Pomares Antonia , Gonzalez‐Vioque Emiliano , Briceño Ana , Cabrera Eva , Cobo‐Marcos Marta , Dominguez Fernando , Gonzalez‐Lopez Esther , Segovia Javier , Lara‐Pezzi Enrique , Garcia‐Pavia Pablo 
Published: August 2022

AbstractAimsTransthyretin amyloid cardiomyopathy (ATTR‐CM) is increasingly recognized as a cause of heart failure in the elderly. Although wild‐type transthyretin amyloidosis is the most frequent form of ATTR‐CM found in the elderly, hereditary transthyretin amyloidosis (ATTRv) can also occur. We sought to determine the prevalence of ATTRv among elderly ATTR‐CM patients, identify predictors of ATTRv and evaluate the clinical consequences of positive genetic testing in this population.Methods and resultsPrevalence of ATTRv in elderly ATTR‐CM patients (≥70 years) was assessed in a cohort of 300 consecutive ATTR‐CM patients (median age 78 years at diagnosis, 82% ≥70 years, 16% female, 99% Caucasian). ATTRv was diagnosed in 35 (12%; 95% confidence interval [CI] 3.1–8.8) and 13 (5.3%; 95% CI 5.6–26.7) patients in the overall cohort and in those ≥70 years, respectively. Prevalence of ATTRv among elderly female patients with ATTR‐CM was 13% (95% CI 2.1–23.5). Univariate analysis identified female sex (odds ratio [OR] 3.66; 95% CI 1.13–11.85; p = 0.03), black ancestry (OR 46.31; 95% CI 3.52–Inf; p = 0.005), eye symptoms (OR 6.64; 95% CI 1.20–36.73; p = 0.03) and polyneuropathy (OR 10.05; 95% CI 3.09–32.64; p < 0.001) as the only factors associated with ATTRv in this population. Diagnosis of ATTRv in elderly ATTR‐CM patients allowed initiation of transthyretin‐specific drug treatment in 5 individuals, genetic screening in 33 relatives from 13 families, and identification of 9 ATTRv asymptomatic carriers.ConclusionsHereditary transthyretin amyloidosis is present in a substantial number of ATTR‐CM patients aged ≥70 years. Identification of ATTRv in elderly patients with ATTR‐CM has clinical meaningful therapeutic and diagnostic implications. These results support routine genetic testing in patients with ATTR‐CM regardless of age.