bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
Authors: Ge Yiyue , Tian Tingzhong , Huang Suling , Wan Fangping , Li Jingxin , Li Shuya , Wang Xiaoting , Yang Hui , Hong Lixiang , Wu Nian , Yuan Enming , Luo Yunan , Cheng Lili , Hu Chengliang , Lei Yipin , Shu Hantao , Feng Xiaolong , Jiang Ziyuan , Wu Yunfu , Chi Ying , Guo Xiling , Cui Lunbiao , Xiao Liang , Li Zeng , Yang Chunhao , Miao Zehong , Chen Ligong , Li Haitao , Zeng Hainian , Zhao Dan , Zhu Fengcai , Shen Xiaokun , Zeng Jianyang 
Published: April 2021

AbstractThe global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). In this study, we developed an integrative drug repositioning framework, which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 can interact with the nucleocapsid (N) protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.
RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-κB hyper-activation and inflammation
Authors: Wu Yaoxing , Ma Ling , Cai Sihui , Zhuang Zhen , Zhao Zhiyao , Jin Shouheng , Xie Weihong , Zhou Lingli , Zhang Lei , Zhao Jincun , Cui Jun 
Published: April 2021

AbstractThe ongoing 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has posed a worldwide pandemic and a major global public health threat. The severity and mortality of COVID-19 are associated with virus-induced dysfunctional inflammatory responses and cytokine storms. However, the interplay between host inflammatory responses and SARS-CoV-2 infection remains largely unknown. Here, we demonstrate that SARS-CoV-2 nucleocapsid (N) protein, the major structural protein of the virion, promotes the virus-triggered activation of NF-κB signaling. After binding to viral RNA, N protein robustly undergoes liquid–liquid phase separation (LLPS), which recruits TAK1 and IKK complex, the key kinases of NF-κB signaling, to enhance NF-κB activation. Moreover, 1,6-hexanediol, the inhibitor of LLPS, can attenuate the phase separation of N protein and restrict its regulatory functions in NF-κB activation. These results suggest that LLPS of N protein provides a platform to induce NF-κB hyper-activation, which could be a potential therapeutic target against COVID-19 severe pneumonia.
The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys
Authors: Jiao Li , Yang Yun , Yu Wenhai , Zhao Yuan , Long Haiting , Gao Jiahong , Ding Kaiyun , Ma Chunxia , Li Jingmei , Zhao Siwen , Wang Haixuan , Li Haiyan , Yang Mengli , Xu Jingwen , Wang Junbin , Yang Jing , Kuang Dexuan , Luo Fangyu , Qian Xingli , Xu Longjiang , Yin Bin , Liu Wei , Liu Hongqi , Lu Shuaiyao , Peng Xiaozhong 
Published: April 2021

AbstractNeurological manifestations are frequently reported in the COVID-19 patients. Neuromechanism of SARS-CoV-2 remains to be elucidated. In this study, we explored the mechanisms of SARS-CoV-2 neurotropism via our established non-human primate model of COVID-19. In rhesus monkey, SARS-CoV-2 invades the CNS primarily via the olfactory bulb. Thereafter, viruses rapidly spread to functional areas of the central nervous system, such as hippocampus, thalamus, and medulla oblongata. The infection of SARS-CoV-2 induces the inflammation possibly by targeting neurons, microglia, and astrocytes in the CNS. Consistently, SARS-CoV-2 infects neuro-derived SK-N-SH, glial-derived U251, and brain microvascular endothelial cells in vitro. To our knowledge, this is the first experimental evidence of SARS-CoV-2 neuroinvasion in the NHP model, which provides important insights into the CNS-related pathogenesis of SARS-CoV-2.
Phenotypic and genetic markers of psychopathology in a population-based sample of older adults
Authors: Gard Arianna M. , Ware Erin B. , Hyde Luke W. , Schmitz Lauren L. , Faul Jessica , Mitchell Colter 
Published: April 2021

AbstractAlthough psychiatric phenotypes are hypothesized to organize into a two-factor internalizing–externalizing structure, few studies have evaluated the structure of psychopathology in older adults, nor explored whether genome-wide polygenic scores (PGSs) are associated with psychopathology in a domain-specific manner. We used data from 6003 individuals of European ancestry from the Health and Retirement Study, a large population-based sample of older adults in the United States. Confirmatory factor analyses were applied to validated measures of psychopathology and PGSs were derived from well-powered genome-wide association studies (GWAS). Genomic SEM was implemented to construct latent PGSs for internalizing, externalizing, and general psychopathology. Phenotypically, the data were best characterized by a single general factor of psychopathology, a factor structure that was replicated across genders and age groups. Although externalizing PGSs (cannabis use, antisocial behavior, alcohol dependence, attention deficit hyperactivity disorder) were not associated with any phenotypes, PGSs for major depressive disorder, neuroticism, and anxiety disorders were associated with both internalizing and externalizing phenotypes. Moreover, the variance explained in the general factor of psychopathology increased by twofold (from 1% to 2%) using the latent internalizing or latent one-factor PGSs, derived using weights from Genomic Structural Equation Modeling (SEM), compared with any of the individual PGSs. Collectively, results suggest that genetic risk factors for and phenotypic markers of psychiatric disorders are transdiagnostic in older adults of European ancestry. Alternative explanations are discussed, including methodological limitations of GWAS and phenotypic measurement of psychiatric outcome in large-scale population-based studies.
The association between latent trauma and brain structure in children
Authors: Jeong Hee Jung , Durham E. Leighton , Moore Tyler M. , Dupont Randolph M. , McDowell Malerie , Cardenas-Iniguez Carlos , Micciche Emily T. , Berman Marc G. , Lahey Benjamin B. , Kaczkurkin Antonia N. 
Published: April 2021

AbstractThe developing brain is marked by high plasticity, which can lead to vulnerability to early life stressors. Previous studies indicate that childhood maltreatment is associated with structural aberrations across a number of brain regions. However, prior work is limited by small sample sizes, heterogeneous age groups, the examination of one structure in isolation, the confounding of different types of early life stressors, and not accounting for socioeconomic status. These limitations may contribute to high variability across studies. The present study aimed to investigate how trauma is specifically associated with cortical thickness and gray matter volume (GMV) differences by leveraging a large sample of children (N = 9270) from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). A latent measure of trauma exposure was derived from DSM-5 traumatic events, and we related this measure of trauma to the brain using structural equation modeling. Trauma exposure was associated with thinner cortices in the bilateral superior frontal gyri and right caudal middle frontal gyrus (pfdr-values < .001) as well as thicker cortices in the left isthmus cingulate and posterior cingulate (pfdr-values ≤ .027), after controlling age, sex, and race/ethnicity. Furthermore, trauma exposure was associated with smaller GMV in the right amygdala and right putamen (pfdr-values ≤ .048). Sensitivity analyses that controlled for income and parental education were largely consistent with the main findings for cortical thickness. These results suggest that trauma may be an important risk factor for structural aberrations, specifically for cortical thickness differences in frontal and cingulate regions in children.
Zbtb16 regulates social cognitive behaviors and neocortical development
Authors: Usui Noriyoshi , Berto Stefano , Konishi Ami , Kondo Makoto , Konopka Genevieve , Matsuzaki Hideo , Shimada Shoichi 
Published: April 2021

AbstractZinc finger and BTB domain containing 16 (ZBTB16) play the roles in the neural progenitor cell proliferation and neuronal differentiation during development, however, how the function of ZBTB16 is involved in brain function and behaviors unknown. Here we show the deletion of Zbtb16 in mice leads to social impairment, repetitive behaviors, risk-taking behaviors, and cognitive impairment. To elucidate the mechanism underlying the behavioral phenotypes, we conducted histological analyses and observed impairments in thinning of neocortical layer 6 (L6) and a reduction of TBR1+ neurons in Zbtb16 KO mice. Furthermore, we found increased dendritic spines and microglia, as well as developmental defects in oligodendrocytes and neocortical myelination in the prefrontal cortex (PFC) of Zbtb16 KO mice. Using genomics approaches, we identified the Zbtb16 transcriptome that includes genes involved in neocortical maturation such as neurogenesis and myelination, and both autism spectrum disorder (ASD) and schizophrenia (SCZ) pathobiology. Co-expression networks further identified Zbtb16-correlated modules that are unique to ASD or SCZ, respectively. Our study provides insight into the novel roles of ZBTB16 in behaviors and neocortical development related to the disorders.
Involvement of the thalamic reticular nucleus in prepulse inhibition of acoustic startle
Authors: You Qiang-long , Luo Zhou-cai , Luo Zheng-yi , Kong Ying , Li Ze-lin , Yang Jian-ming , Li Xiao-wen , Gao Tian-ming 
Published: April 2021

AbstractThalamic reticular nucleus (TRN) is a group of inhibitory neurons surrounding the thalamus. Due to its important role in sensory information processing, TRN is considered as the target nucleus for the pathophysiological investigation of schizophrenia and autism spectrum disorder (ASD). Prepulse inhibition (PPI) of acoustic startle response, a phenomenon that strong stimulus-induced startle reflex is reduced by a weaker prestimulus, is always found impaired in schizophrenia and ASD. But the role of TRN in PPI modulation remains unknown. Here, we report that parvalbumin-expressing (PV+) neurons in TRN are activated by sound stimulation of PPI paradigm. Chemogenetic inhibition of PV+ neurons in TRN impairs PPI performance. Further investigations on the mechanism suggest a model of burst-rebound burst firing in TRN-auditory thalamus (medial geniculate nucleus, MG) circuitry. The burst firing is mediated by T-type calcium channel in TRN, and rebound burst firing needs the participation of GABAB receptor in MG. Overall, these findings support the involvement of TRN in PPI modulation.
Simulations of the Biermann battery mechanism in two-fluid partially ionised plasmas
Authors: Martínez-Gómez D. , Popescu Braileanu B. , Khomenko E. , Hunana P. 
Published: April 2021

Context. In the absence of an initial seed, the Biermann battery term of a non-ideal induction equation acts as a source that generates weak magnetic fields. These fields are then amplified via a dynamo mechanism. The Kelvin-Helmholtz instability is a fluid phenomenon that takes place in many astrophysical scenarios and can trigger the action of the Biermann battery and dynamo processes.
Aims. We aim to investigate the effect of the ionisation degree of the plasma and the interaction between the charged and neutral species on the generation and amplification of magnetic fields during the different stages of the instability.
Methods. We use the two-fluid model implemented in the numerical code Mancha-2F. We perform 2D simulations starting from a configuration with no initial magnetic field and which is unstable due to a velocity shear. We vary the ionisation degree of the plasma and we analyse the role that the different collisional terms included in the equations of the model play on the evolution of the instability and the generation of magnetic field.
Results. We find that when no collisional coupling is considered between the two fluids, the effect of the Biermann battery mechanism does not depend on the ionisation degree. However, when elastic collisions are taken into account, the generation of magnetic field is increased as the ionisation degree is reduced. This behaviour is slightly enhanced if the process of charge-exchange is also considered. We also find a dependence on the total density of the plasma related to the dependence on the coupling degree between the two fluids. As the total density is increased, the results from the two-fluid model converge to the predictions of single-fluid models.
Conclusions. The charged-neutral interaction in a partially ionised plasmas has a non-negligible effect on the Biermann battery mechanism and it effectively enhances the generation of a magnetic field. In addition, single-fluid models, which assume a very strong coupling between the two species, may overestimate the contribution of this interaction in comparison with two-fluid models.
Schmerz und Angst bei der Hämodialyseshuntpunktion
Authors: Koppelmann Frank 
Published: April 2021

ZUSAMMENFASSUNGDer Shunt eines Dialysepatienten wird pro Jahr bis zu 300-mal punktiert. Angst vor der Punktion und Schmerzen bei der Punktion sind ein wenig behandeltes, aber dennoch vorhandenes Problem, welches genauer analysiert werden sollte. Lösungsvorschläge und Ideen diesbezüglich sind rar gesät und wenn vorhanden dann meist sehr spezifisch, nicht verallgemeinerbar und oft aus der Situation heraus geboren. Das Augenmerk dieses Beitrags liegt auf einer Definition von dem, was Angst und Schmerzen sind, sowie dem Erkennen von Schmerzen und Ängsten und bietet eine Auswahl möglicher Maßnahmen für die Patienten, um diese zu erkennen und zu lindern. Die Ergebnisse der Patientenbefragung zeigen, dass eine Mehrheit der Patienten keine Angst vor der Punktion hat, es aber definitiv eine Minderheit der Befragten gibt, die Angst als ein Problem wahrnehmen. Schmerzen bei der Punktion erleben über die Hälfte der Patienten, wenn auch nicht bei jeder Punktion.
Rufbereitschaftsdienst Peritonealdialyse in einem ambulanten Dialysezentrum
Authors: Schick Sandra 
Published: April 2021

ZUSAMMENFASSUNGDie Peritonealdialyse ist ein wichtiger Teil der Heimdialyseverfahren und bietet viele Vorteile für den Patienten. Trotzdem gibt es viele Dialysezentren in Deutschland, die keine oder nur wenige Peritonealdialysepatienten betreuen. Infolgedessen ist es für den Großteil des nephrologischen Personals nicht möglich, Routine in diesem Bereich zu erwerben. Durch Anbindung des PHV-Dialysezentrums Biberach an die Sana-Klinik kommt es regelmäßig zu Einsätzen im Rufbereitschaftsdienst auf der Intensivstation bei Hämodialysepatienten. Bei Zwischenfällen im Bereich der Peritonealdialyse, die dementsprechend selten vorkommen, kann man bei vielen Mitarbeitern des Rufbereitschaftsdienstes Unsicherheiten und Ängste beobachten. Die vorliegende Arbeit überprüft anhand eines Fragebogens die Unsicherheiten, Ursachen von Angst und die Gründe zurückliegender PD-Rufbereitschaftseinsätze. Zudem wird der persönliche Schulungsbedarf ermittelt. Ableitend aus den Ergebnissen wurden Arbeitsanleitungen erstellt und Mitarbeiterschulungen durchgeführt. Um die Ergebnisse der Arbeit sichtbar zu machen, wurde zum Abschluss des Projekts ein zweiter Fragebogen an die Mitarbeiter ausgeteilt. Die Auswertung dieser Befragung ergab, dass die Arbeitsanleitungen bei einem Peritonealdialyseeinsatz im Rufbereitschaftsdienst zwar Sicherheit vermitteln, regelmäßige Schulungen und praktische Übungen aber unerlässlich und gewünscht sind. Sicherheit und Wissen im Bereich der Peritonealdialyse zu vermitteln, ist ein kontinuierlicher Prozess und fordert ein gut ausgearbeitetes Schulungskonzept.
Recurrent Spontaneous Miscarriage: a Comparison of International Guidelines
Authors: Vomstein Kilian , Aulitzky Anna , Strobel Laura , Bohlmann Michael , Feil Katharina , Rudnik-Schöneborn Sabine , Zschocke Johannes , Toth Bettina 
Published: April 2021

AbstractWhile roughly 30% of all women experience a spontaneous miscarriage in their lifetime, the incidence of recurrent (habitual) spontaneous miscarriage is 1 – 3% depending on the employed definition. The established risk factors include endocrine, anatomical, infection-related, genetic, haemostasis-related and immunological factors. Diagnosis is made more difficult by the sometimes diverging recommendations of the respective international specialist societies. The present study is therefore intended to provide a comparison of existing international guidelines and recommendations. The guidelines of the ESHRE, ASRM, the DGGG/OEGGG/SGGG and the recommendations of the RCOG were analysed. It was shown that investigation is indicated after 2 clinical pregnancies and the diagnosis should be made using a standardised timetable that includes the most frequent causes of spontaneous miscarriage. The guidelines concur that anatomical malformations, antiphospholipid syndrome and thyroid dysfunction should be excluded. Moreover, the guidelines recommend carrying out pre-conception chromosomal analysis of both partners (or of the aborted material). Other risk factors have not been included in the recommendations by all specialist societies, on the one hand because of a lack of diagnostic criteria (luteal phase insufficiency) and on the other hand because of the different age of the guidelines (chronic endometritis). In addition, various economic and consensus aspects in producing the guidelines influence the individual recommendations. An understanding of the underlying decision-making process should lead in practice to the best individual diagnosis and resulting treatment being offered to each couple.
Wenn eine Schwangerschaft lebensbedrohlich wird – Eklampsie im Rettungsdienst
Authors: Volberg Christian 
Published: April 2021

ZusammenfassungEine 24-jährige schwangere Patientin hat aufgrund ihres alternativen Lebensstils die Mitgliedschaft in der gesetzlichen Krankenversicherung aufgegeben und während der Schwangerschaft keine
gynäkologische oder geburtshilfliche Vorsorgeuntersuchung durchführen lassen. Im 3. Trimenon kommt es zu einer Verschlechterung des Allgemeinzustandes mit Entwicklung von peripheren Ödemen
und zunehmender Lichtempfindlichkeit. Die Fallvorstellung beschreibt den gefährlichen und komplikationsreichen Verlauf einer fehlenden Schwangerschaftsüberwachung mit schwerwiegenden Folgen
für Mutter und Kind.
Kosten der Nachsorge von Patienten mit hämatologischen Neoplasien
Authors: Hörster Laura , Neusser Silke , Trautner Annika , Pahmeier Kathrin , Lax Hildegard , Merkel-Jens Anja , Lehmann Nils , Jöckel Karl-Heinz , Baum Julia , Dührsen Ulrich , Wasem Jürgen , Neumann Anja 
Published: April 2021

Zusammenfassung
Zielsetzung Im Gegensatz zu hämatologischen Neoplasien im Kindesalter gibt es für Erwachsene mit diesen Erkrankungen wenige bis keine einheitlichen Nachsorgemuster und dementsprechend auch keine rational begründeten Nachsorgepläne. Des Weiteren wurden bislang keine Studien zu den mit der Nachsorge einhergehenden Kosten veröffentlicht. Die vorliegende Studie dient zur Erfassung des Ressourcenverbrauchs und der damit einhergehenden Kosten von erwachsenen Patienten.
Methodik Die Daten des Ressourcenverbrauchs wurden 2014 retrospektiv für die letzten 12 Monate mittels eines standardisierten Fragebogens erfasst. Die Krankheitskosten (direkte medizinische sowie indirekte Kosten) wurden aus der gesellschaftlichen Perspektive ermittelt. Das Jahr 2014 dient als Basisjahr für die Berechnung der Preise. Zur Ermittlung der indirekten Kosten (Erwerbsminderung, Arbeitsunfähigkeit) wurde der Friktionskostenansatz mit einer Friktionsperiode von 90 Tagen herangezogen. Weiterhin erfolgte ein Vergleich mit Hilfe des Humankapitalansatzes.
Ergebnisse Insgesamt nahmen 1531 Patienten an der gesundheitsökonomischen Erhebung teil. 89,4 % der Teilnehmer wiesen im Erfassungszeitraum mindestens einen ambulanten Arztkontakt auf. 235 Teilnehmern (15,3 %) wurde mindestens ein der Nachsorge zuzuordnendes Medikament verabreicht. 9,7 % der Studienteilnehmer gaben keinerlei Inanspruchnahme aufgrund von Nachsorge der Krebserkrankung an. Insgesamt ergaben sich direkte medizinische Kosten von durchschnittlich ca. 3627 € pro Patient. Die indirekten Krankheitskosten beliefen sich unter Verwendung des Friktionskostenansatzes auf ca. 165 € pro Patient.
Schlussfolgerung Arzneimittelkosten verursachen mit etwa 60 % den Großteil der direkten Nachsorgekosten bei Patienten mit hämatologischen Neoplasien. Nach der zugrundeliegenden Erkrankung aufgeschlüsselt weisen myeloproliferative Erkrankungen mit einem Anteil von fast 60 % die höchsten Gesamtkosten auf. Unter Verwendung des Friktionskostenansatzes lassen sich die Nachsorgekosten in 95,7 % direkte Kosten und 4,3 % indirekte Kosten unterteilen. 9,7 % der Studienteilnehmer geben keinerlei Inanspruchnahme aufgrund von Nachsorge der Krebserkrankung an und scheinen somit komplett durch das Nachsorgesystem zu fallen.
Tailor-Made Psychosocial Intervention for the Caregivers in Emergency and Trauma Care Center
Authors: Kanmani T.R. , Raju Birudu , Konar Subhas , Shukla Dhaval , Kukkehalli Raghavendra 
Published: April 2021

Abstract

Introduction The caregiver’s psychosocial problems are unnoticed in the emergency and trauma care center. Therefore, the study objective was to understand the impact of psychoeducation and psychosocial intervention on traumatic brain injury (TBI) caregivers during hospitalization.

Methodology The study adopted a descriptive research design. Sixty-three (n = 63) consented caregivers were recruited by using a cross-sectional survey method. Two separate checklists were used to collect the psychosocial problems in emergency and trauma care as well as to know the satisfaction levels of caregivers after the intervention. R free 3.0.1 software was used to calculate the frequency and percentage.

Results The caregiver’s mean age was 39 years (39.46 ± 16.22). The majority of the caregivers were males (45; 71.4%) working as daily wagers (42; 66.7%). Caregivers experienced psychosocial problems, that is, depression, anxiety, stress, unable to handle crisis, grief, lack of coping skills (57; 90.5%), emotional distress (57; 90.5%), financial constraints (45; 71.1%), and need for referral services (45; 71.1%). Tailor-made psychosocial interventions were provided to the caregivers.

Conclusion To conclude, there is a greater need to provide psychosocial intervention and train the caregivers to provide care for TBI survivors during hospitalization. There is a need to develop the uniform standard operating procedure for medical and psychiatric social workers in providing psychosocial care in emergency and trauma care setting.