bluuebunny/crossref_metadata_2025 huggingface dataset:
A DESTITUIÇÃO DO "SOCIAL": Estado, governo e políticas sociais
Authors: Ivo Anete Brito Leal
Published: August 2022

A transição democrática, nas décadas de 80/90, alterou, em tempos e ritmos variados, as tradicionais relações entre o Estado e a sociedade na América Latina. De um lado, observa-se a afirmação de um sujeito popular e a formação do espaço público; de outro, a integração à acumulação globalizada, e os ajustes afetam o pacto social anteriormente prevalecente, agravando as formas de coesão e integração social, como crise de governabilidade. Nesse contexto, observase uma reconversão do tratamento da ‘questão social’, que passa de política redistributiva, produtora de justiça social, para um tratamento mitigador, setorializado, e focalizado da pobreza, dentro de um modelo excludente. Este artigo discute essa questão, analisando: (i) a governabilidade como crise de racionalidade; (ii) os fatores conjunturais e históricoculturais que singularizam a política nessa região; (iii) a despolitização da relação entre sociedade e Estado, inscrita nos diagnósticos da governabilidade; (iv) os limites e ambigüidades da reconversão do ‘novo social’. PALAVRAS-CHAVES: Transformações do Estado, governabilidade, reforma do Estado, política social, América Latina. THE SOCIAL ISSUE DESTITUTION: state, government and social policies The demographic transition in the 80s and 90s changed the traditional State and society relationships, in Latin America in different times and pace. It was possible to observe, on one hand, the confirmation of a popular subject and public space formation; on the other hand how the integration with the globalized accumulation and adjustment affect the existing social pact, worsening the forms of cohesion and social integration as a governance crisis. In this context, a re-conversion of the social issue treatment can be observed, which ranges from a redistribution policy that fosters social justice, to a mitigating, compartmentalized treatment that concentrated on poverty in the scope of an excluding model. The paper discusses this issue analyzing: 1) governance as a rationality crisis; II) the state of affairs and historiccultural factors that make the policy unique in this region; III) the depoliticizing relationship between society and State, inscribed in the governance diagnosis, and; iv) the limits and ambiguity of the ‘new social’ re-conversion. KEY WORDS: State transformations, governance, state reform, social polity and Latin America. Publicação Online do Caderno CRH: http://www.cadernocrh.ufba.br
ESTADO E DEMOCRACIA NO GOVERNO DO PT E NOS GOVERNOS PETISTAS
Authors: De Souza Lincoln Moraes
Published: August 2022

O objetivo central do trabalho é apreender as propostas de Estado e democracia do programa partidário do PT e nas administrações petistas. Para tanto, analisa-se o Programa Nacional do Partido e como o mesmo foi rebatido na estrutura e funcionamento de seus governos municipais. Foram observadas e estudadas diferentes experiências e os respectivos significados teórico-políticos, bem como as dificuldades, dilemas e inflexões na implementação das propostas programáticas nacionais no plano local. PALAVRAS-CHAVE: Estado e Democracia, partido político, Partido dos Trabalhadores, poder local, Brasil. STATE AND DEMOCRACY IN THE WORKERS’ PARTY (PT) PROGRAM AND IN THE WORKERS’ PARTY GOVERNMENT The central objective of the paper is to grasp the state and democracy proposals of the Workers’ Party Program and administrations. To achieve its goal, it analyzes the National Program of the Party and how it was rejected in terms of structure and operation of its local government. Different experiences and their respective theoretical and political meanings were observed and studied, as well as the difficulties, dilemmas and inflections for implementing the national proposals at a local level. KEY WORDS: State and Democracy, political party, Workers’ Party, Local Power, Brazil Publicação Online do Caderno CRH: http://www.cadernocrh.ufba.br
Treating Alcohol Use Disorder With Hallucinogens—Renewed Interest After a 50-Year Hiatus
Authors: Kranzler Henry R. , Hartwell Emily E.
Published: August 2022

This Viewpoint discusses the use of hallucinogens to treat alcohol use disorder.
Scientific Influence of R01 Grants Issued to Department of Surgery Investigators, 2000 to 2015
Authors: Kolb Bradley , Kim Dustin
Published: August 2022

This observational study uses citation rates to measure the influence of National Institutes of Health R01 grants issued to department of surgery investigators and compared them according to whether the investigator was a surgeon-scientist or a research-scientist.
ExacTrac Dynamic workflow evaluation: Combined surface optical/thermal imaging and X‐ray positioning
Authors: Da Silva Mendes Vanessa , Reiner Michael , Huang Lili , Reitz Daniel , Straub Katrin , Corradini Stefanie , Niyazi Maximilian , Belka Claus , Kurz Christopher , Landry Guillaume , Freislederer Philipp
Published: August 2022

In modern radiotherapy (RT), especially for stereotactic radiotherapy or stereotactic radiosurgery treatments, image guidance is essential. Recently, the ExacTrac Dynamic (EXTD) system, a new combined surface‐guided RT and image‐guided RT (IGRT) system for patient positioning, monitoring, and tumor targeting, was introduced in clinical practice. The purpose of this study was to provide more information about the geometric accuracy of EXTD and its workflow in a clinical environment. The surface optical/thermal‐ and the stereoscopic X‐ray imaging positioning systems of EXTD was evaluated and compared to cone‐beam computed tomography (CBCT). Additionally, the congruence with the radiation isocenter was tested. A Winston Lutz test was executed several times over 1 year, and repeated end‐to‐end positioning tests were performed. The magnitude of the displacements between all systems, CBCT, stereoscopic X‐ray, optical‐surface imaging, and MV portal imaging was within the submillimeter range, suggesting that the image guidance provided by EXTD is accurate at any couch angle. Additionally, results from the evaluation of 14 patients with intracranial tumors treated with open‐face masks are reported, and limited differences with a maximum of 0.02 mm between optical/thermal‐ and stereoscopic X‐ray imaging were found. As the optical/thermal positioning system showed a comparable accuracy to other IGRT systems, and due to its constant monitoring capability, it can be an efficient tool for detecting intra‐fractional motion and for real‐time tracking of the surface position during RT.
Large Memory Window of van der Waals Heterostructure Devices Based on MOCVD‐Grown 2D Layered Ge4Se9
Authors: Noh Gichang , Song Hwayoung , Choi Heenang , Kim Mingyu , Jeong Jae Hwan , Lee Yongjoon , Choi Min‐Yeong , Oh Saeyoung , Jo Min‐kyung , Woo Dong Yeon , Jo Yooyeon , Park Eunpyo , Moon Eoram , Kim Tae Soo , Chai Hyun‐Jun , Huh Woong , Lee Chul‐Ho , Kim Cheol‐Joo , Yang Heejun , Song Seungwoo , Jeong Hu Young , Kim Yong‐Sung , Lee Gwan‐Hyoung , Lim Jongsun , Kim Chang Gyoun , Chung Taek‐Mo , Kwak Joon Young , Kang Kibum
Published: August 2022

Van der Waals (vdW) heterostructures have drawn much interest over the last decade owing to their absence of dangling bonds and their intriguing low‐dimensional properties. The emergence of 2D materials has enabled the achievement of significant progress in both the discovery of physical phenomena and the realization of superior devices. In this work, the group IV metal chalcogenide 2D‐layered Ge4Se9 is introduced as a new selection of insulating vdW material. 2D‐layered Ge4Se9 is synthesized with a rectangular shape using the metalcorganic chemical vapor deposition system using a liquid germanium precursor at 240 °C. By stacking the Ge4Se9 and MoS2, vdW heterostructure devices are fabricated with a giant memory window of 129 V by sweeping back gate range of ±80 V. The gate‐independent decay time reveals that the large hysteresis is induced by the interfacial charge transfer, which originates from the low band offset. Moreover, repeatable conductance changes are observed over the 2250 pulses with low non‐linearity values of 0.26 and 0.95 for potentiation and depression curves, respectively. The energy consumption of the MoS2/Ge4Se9 device is about 15 fJ for operating energy and the learning accuracy of image classification reaches 88.3%, which further proves the great potential of artificial synapses.
Ferromagnetic Order in Semiconducting Cr‐Doped α‐MnTe Nanosheets Grown by Chemical Vapor Deposition
Authors: Zhang Zheshan , Dong Xinyue , Gao Zhansheng , Chen Jiabiao , Wang Bing , Fu Huixia , Du Yaping , Luo Feng , Wu Jinxiong
Published: August 2022

Ferromagnetic semiconductors (FMSs) have been extensively investigated to fulfill the prospect of simultaneous control spin and charge of electron over the past decades. However, it is still highly desirable to identify new ferromagnetic semiconductors with robust and reliable sign of coexistence of semi‐conductivity and ferromagnetism, especially for those ultrathin film systems with great potential for electrical gating. Here, ultrathin Cr‐doped α‐MnTe nanosheets can be readily prepared via a facile chemical vapor deposition (CVD) method, which sustain the crystal structure of parent α‐MnTe but exhibit utterly changed electrical and magnetic properties. Derived from anomalous Hall measurements, the CVD‐grown sample presented a robust out‐of‐plane ferromagnetic order with Curie temperature of ≈210 K and a large coercivity >3.5 T at 2 K. Additionally, Cr‐doped α‐MnTe nanosheets show tunable ferromagnetism and different gating effects with varied thicknesses. The theoretical calculation is performed to explain the origin of its ferromagnetism and semi‐conductivity, probably attributed to the specific antiferromagnetic arrangement of each Mn/Cr plane and non‐zero net magnetic moment with Cr introducing. The work sheds new light on the development of dilute ferromagnetic semiconductors and spintronics.
Current status of liver transplantation for non‐B non‐C liver cirrhosis and hepatocellular carcinoma
Authors: Nishio Takahiro , Ito Takashi , Hata Koichiro , Taura Kojiro , Hatano Etsuro
Published: August 2022

Recently, non‐B non‐C chronic liver diseases, including alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), have markedly increased worldwide. Liver transplantation (LT) is an effective curative therapy for hepatocellular carcinoma (HCC) as well as decompensated liver cirrhosis. In Japan, where the source of liver grafts is strongly dependent on living donors, efforts have been made to unify the indications for eligibility of HCC patients for LT, leading to the development of 5‐5‐500 criteria. Along with the expansion of eligibility for LT, the current changing trends in underlying liver diseases of LT recipients, which are related to the rising tide of non‐B non‐C cirrhosis and HCC, are highlighting the importance of peri‐transplant management of patients with various comorbidities. The post‐LT prognosis of patients with ALD is significantly affected by de novo malignancies and metabolic syndrome‐related complications as well as posttransplant alcohol relapse. NAFLD/NASH patients often suffer from obesity, type 2 diabetes mellitus, and other metabolic syndrome‐related disorders, and nonneoplastic factors such as cardiovascular events and recurrence of NAFLD/NASH have a significant impact on post‐LT outcomes. Patient management in the peri‐transplant period as well as risk assessment for LT are key to improving post‐LT outcomes in the era of a growing number of cases of LT for non‐B non‐C liver diseases.
Effects of spot size on biomarker levels of field‐collected dried blood spots: A new algorithm for exact dried blood spot size measurement
Authors: Groh Rebecca , Weiss Luzia M. , Börsch‐Supan Martina , Börsch‐Supan Axel
Published: August 2022

Objectives

The quality of blood values analyzed from survey‐collected dried blood spot (DBS) samples is affected by fieldwork conditions, particularly spot size. We offer an image‐based algorithm that accurately measures the area of field‐collected DBS and we investigate the impact of spot size on the analyzed blood marker values.

Methods

SHARE, a pan‐European study, collected 24 000 DBS samples in 12 countries in its sixth wave. Our new algorithm uses photographs of the DBS samples to calculate the number of pixels of the blood‐covered area to measure the spot sizes accurately. We ran regression models to examine the association of spot size and seven DBS analytes. We then compared the application of our new spot‐size measures to common spot‐size estimation.

Results

Using automated spot‐size measurement, we found that spot size has a significant effect on all markers. Smaller spots are associated with lower measured levels, except for HbA1c, for which we observe a negative effect. Our precisely measured spot sizes explain substantially more variance of DBS analytes compared to commonly used spot‐size estimation.

Conclusion

The new algorithm accurately measures the size of field‐collected DBS in an automated way. This methodology can be applied to surveys even with very large numbers of observations. The measured spot sizes improve the accuracy of conversion formulae that translate blood marker values derived from DBS into venous blood values. The significance of the spot‐size effects on biomarkers in DBS should also incentivize the improvement of fieldwork training and monitoring.
Novel thiadiazole‐derived Schiff base ligand and its transition metal complexes: Thermal behaviour, theoretical study, chemo‐sensor, antimicrobial, antidiabetic and anticancer activity
Authors: Radha Venkittapuram Palaniswamy , Prabakaran Mayakrishnan
Published: August 2022

Novel thiadiazole‐based Schiff base ligand (L) and their Co(II), Ni(II), Cu(II) and Zn(II) metal complexes have been prepared and characterized using elemental analysis, IR, 1H‐NMR, 13C‐NMR, UV‐vis spectroscopy, EPR, thermal analysis, magnetic moment and conductometric measurements. Based on the above studies, the metal complexes were found to exhibit octahedral geometry except that of Zn(II) complex, which is tetrahedral. The thermal stability and the presence of coordinated water molecules of the metal complexes were investigated by thermogravimetric analysis. Geometry optimization of the ligand and its Zn(II) complex was performed using B3LYP functional with LANL2DZ basis set. The HOMO–LUMO energy gap, molecular properties, NLO, polarizability and MEP were theoretically calculated. The fluorescence spectra of the ligand revealed that the sensor could detect K+ ions over the pool of other metal ions. The Schiff base ligand and its metal complexes have been screened for their antimicrobial activity against different bacterial and fungal species using inhibition zone technique and by well diffusion methods. The results revealed that metal complexes have more activity than that of the ligand. The anticancer activities of Co(II) and Cu(II) complexes have been studied towards breast cancer (MCF‐7) cell lines. The Co(II) and Cu(II) complexes have also been evaluated for in vitro α‐amylase inhibitory activity.
‘Rigid‐soft’ synergistic effects to improve the microstructure and superflexibility properties of aramid nanofiber aerogel
Authors: Li Jiaoyang , Lu Zhaoqing , Huang Jizhen , Hua Li
Published: August 2022

Designing aramid nanofiber (ANF) aerogel with excellent microstructure and high thermal insulation property is benefit for applications in integrated thermal management system. To obtain a structurally controllable ANF‐based aerogel, the cellulose nanofiber (CNF) and poly (vinyl alcohol) (PVA) were ‘stiff–soft’ synergistic to improve the microstructure. The cobweb like structures distributed in the honeycomb layered pores of the CNF/PVA/ANF composite aerogel which was conducive to the performance and application of composite aerogel. The resulting CNF1/PVA1/ANF composite aerogels are highly porous (99.12%) and tiny volume shrinkage (4.65%), leading to excellent thermal insulation performance (26.83 mW/m·K). The ‘stiff–soft’ feature endows the composite aerogels high flexibility as well as large compression strength. These favorable multi‐features make the CNF/PVA/ANF composite aerogels ideal advanced material for aerospace, industrial, and commercial applications.
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

The 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

This 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

Teaching 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

Astragalus 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

Arsenic 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

Coding 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

The 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

Linezolid, 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

A 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

The 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

In 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

Background

The 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.

Results

Cichlid 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.

Conclusions

Differential 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

Objective

This 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.

Method

The 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.

Results

Across 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.

Discussion

This 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 Significance

Based 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

Aims

Transthyretin 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 results

Prevalence 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.

Conclusions

Hereditary 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.
Sumatriptan prevents central sensitization specifically in the trigeminal dermatome in humans
Authors: Peng Kuan‐Po , Jürgens Tim , Basedau Hauke , Ortlieb Luise , May Arne
Published: August 2022

Background

The exact mechanism and site of action of triptans in aborting migraine attacks remain under debate. We hypothesized that the clinical efficacy of triptans lies in aborting central sensitization and focused on the question of why triptans are headache specific, that is highly effective in migraine and cluster headache and ineffective in extracephalic pain.

Methods

Forty healthy participants were enrolled in this double‐blinded, randomized, placebo‐controlled study. The effect of sumatriptan (n = 20) versus placebo (n = 20) was investigated in a trigeminal (V1) versus an extracephalic dermatome (forearm) using a topical capsaicin sensitization model. Capsaicin‐induced primary and secondary hyperalgesia were evaluated using quantitative sensory testing.

Results

After capsaicin application, primary hyperalgesia developed in both the sumatriptan and placebo groups in both dermatomes. However, sumatriptan exclusively prevented secondary hyperalgesia in the V1 dermatome but not on the forearm. Placebo exerted no effects on secondary hyperalgesia in both trigeminal and extracephalic dermatomes. Additionally, sumatriptan reduced the flare size exclusively in the V1 dermatome.

Conclusions

Our data suggest that sumatriptan reduces central sensitization (secondary hyperalgesia) without modulating peripheral sensitization (primary hyperalgesia) in a human pain model of capsaicin‐induced sensitization. Moreover, despite a systemic administration of sumatriptan, the modulatory effects are trigeminal specific, echoing the clinical effect of triptans in aborting headaches, but not extracephalic pain.

Significance

Our data suggest that triptans exert their efficacy by suppressing central sensitization. By revealing a dermatome‐specific modulation, our study demonstrates a previously unrecognized interaction between the pharmacodynamics of triptans and the trigeminal nociceptive system that provides new insight into how triptans may work in aborting headache attacks.
Data science and climate risk analytics
Authors: Sain Stephan R.
Published: August 2022

With influences from different communities, data science has evolved to provide insights in many different data‐driven environments, including climate science. In this article, a brief review of data science and its connection to climate science will be presented. Additionally, two data science pipelines for quantifying risks from climate change are discussed. These pipelines focus on flooding due to tropical cyclone storm surge and changes in the distribution of temperature or precipitation or wind due to climate change via downscaling climate models. Finally, some key data science research areas in climate risk analytics are discussed.
Experimental study on the mechanical properties, acoustic emission characteristics, and permeability evolution of sandstone under triaxial hydromechanical coupling
Authors: Wang Guozhu , Song Lei , Wang Qirui , Tian Zhuangcai , Fan Junqi , Wang Yu , Ren Jianwei , Yang Weihao , Li Haipeng , Zhang Mingwei , Shen Honglei
Published: August 2022

In situ stress and groundwater have important effects on the deformation and stability of deep underground rock masses. Therefore, it is extremely important to study the mechanical properties and permeability evolutionary processes of rocks under hydromechanical (HM) coupling. The purpose of this study was to investigate the mechanical properties and permeability evolution of sandstone using triaxial compression tests under different confining and seepage pressures. The test results show that the confining pressure can increase the strength of sandstone, whereas the seepage pressure has the opposite effect. The initial and maximum permeabilities were positively correlated with seepage pressure and negatively correlated with confining pressure. The confining and seepage pressures had little effect on the change in initial permeability. As a common parameter of acoustic emission (AE), cumulative AE counts can intuitively reflect the permeability evolutionary process in the sandstone failure process. A permeability evolutionary early warning model for the sandstone failure process under HM coupling is proposed. The results are helpful for understanding the influence of in situ stress and seepage pressure on deep sandstone and the permeability evolutionary mechanism, and they can be used to provide early warning of water inrush disasters in deep underground structures.
Vertical wind speed extrapolation model using long short‐term memory and particle swarm optimization
Authors: Al‐Shaikhi Ali , Nuha Hilal , Mohandes Mohamed , Rehman Shafiqur , Adrian Monterico
Published: August 2022

Investigating the potential for deploying a wind farm requires accurate knowledge of the vertical profile of wind speed (WS), both temporal and with height. Commonly, WS estimations at different heights involves calculating site‐dependent parameters such as roughness length, atmospheric conditions, and wind shear coefficient. This study proposes a hybrid model to estimate WS at different heights based on measurements at lower heights using particle swarm optimization and long short‐term memory (PSO‐LSTM). The training procedure consists of two steps, namely the Levenberg–Marquardt (LM) and the PSO, to minimize the mean squared error. To perform vertical extrapolation, the PSO‐LSTM utilizes the measured WS at 10‐40 m heights to predict WS at 50 m. The predicted results at 50 m are then utilized along with the measured WS at 10–40 to extrapolate WS to 60 m. This process continues until the extrapolation of WS at 120 m is made. The PSO is compared with other optimization methods like genetic algorithm (GA), tuna swarm optimization (TSO), grey wolf optimization (GWO), sparrow search algorithm (SSA), and bald eagle search (BES) on improving the LSTM accuracy. The performance of the PSO‐LSTM is compared with the standard LSTM, feedforward neural network and the logarithmic law (LogLaw) based estimation. The extrapolated values obtained using these methods are compared with LiDAR system‐based measurements. The proposed method outperformed the other methods.
Antagonism of nonaflatoxigenic Aspergillus flavus isolated from peanuts against aflatoxigenic A. flavus growth and aflatoxin B1 production in vitro
Authors: Rahman Mohd Azuar Hamizan , Selamat Jinap , Samsudin Nik Iskandar Putra , Shaari Khozirah , Mahror Norlia , John Joshua Mark
Published: August 2022

Aspergillus section Flavi constitutes several species of opportunistic fungi, notable among them are A. flavus and A. parasiticus, capable of surviving harsh conditions and colonizing a wide range of agricultural products pre‐ and postharvest. Physical and chemical control methods are widely applied in order to mitigate the invasion of A. flavus in crops. However, physical control is not suitable for large scale and chemical control often leads to environmental pollution, whereas biological control offers a safer, environmentally friendly, and economical alternative. The present study aimed to investigate the antagonism of several non‐aflatoxigenic A. flavus strains against the aflatoxigenic ones in vitro (semisynthetic peanut growth medium; MPA) in terms of colony growth rate and AFB1 inhibition. Different peanut concentrations were used to obtain the optimum peanut concentration in the formulated growth medium. A dual culture assay was performed to assess the antagonism of nonaflatoxigenic strains against the aflatoxigenic ones. Results revealed that 9% MPA exhibited the highest growth and AFB1 inhibition by nonaflatoxigenic strains. It was also found that different nonaflatoxigenic strains exhibited different antagonism against the aflatoxigenic ones which ranged from 11.09 ± 0.65% to 14.06 ± 0.14% for growth inhibition, and 53.97 ± 2.46% to 72.64 ± 4.54% for AFB1 inhibition. This variability could be due to the difference in antagonistic metabolites produced by different nonaflatoxigenic strains assessed in the present study. Metabolomics study to ascertain the specific metabolites that conferred the growth and aflatoxin inhibition is ongoing.