bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Psychological Impact of Torture and State Repression in Türkiye between 2015 and 2018: Reports from Turkish Refugees Seeking Asylum in Germany
Authors: Tambini Stollwerck Estella Alejandra , Sarikaya Ilkem , Yen Kathrin , Friederich Hans-Christoph , Nikendei Christoph 
Published: October 2023

AbstractTorture seeks to undermine not only the physical and emotional well-being of an individual but to damage the coherence of entire communities. Thus, torture and state repression are used to weaken entire subpopulations. After the failed coup d’état in Türkiye in 2016 and during the subsequently following state of emergency that lasted until 2018, allegations of torture and other degrading treatment in Türkiye spread widely. Since then, the number of asylum-seekers in Germany has risen considerably.This paper analyses the reports of twenty Turkish citizens that fled to Germany to seek asylum in the aftermath of the events. In semi-structured interviews held in Turkish, we assessed the experiences of torture and state repression, psychological consequences, and the current well-being and living situation.All interviewees described illicit experiences with violence from state authorities and government supporters, especially while under arrest. Though the methods varied, there was a constant pattern of imbalance of power. The psychological impact of these methods were present after relocation in Germany and included signs of PTSD, anxiety disorders, and major depression.The reports of torture, state repression, and their psychological impact emphasise the importance for policy makers to address the prevention of human rights violations and support the needs of survivors.
Prevalence of Depression among Senior Secondary School Students in Enugu Metropolis
Authors: Okeke Nzubechukwu Gift , Okenyi Johncross Ogbonna , Ohanu Eberechi Cyprian , Okeke Chidera 
Published: October 2023

ABSTRACTBackgroundDepression is defined as a state of low mood and aversion to activity. A mental health disorder characterized by persistent low mood or loss of interest in activities causing significant impairment in daily life. Depression amongst secondary school students is an issue that is often ignored. It is frequently unrecognized when present in adolescents who make up the population of secondary school students (age 10-19 years). In our environment, studies have reported that 21.2% of Nigerian adolescents are suffering from mild to moderate depression and depression when left unchecked and untreated, takes a toll on the quality of life of individuals affected. This is why this study was conducted to determine the prevalence of depression among senior secondary school students in Enugu metropolis, to create proper awareness and sensitize people involved and the public on this menace.MethodA descriptive cross-sectional study was carried out with a sample size of 270 secondary school students across 10 secondary schools in Enugu metropolis. The population of 270 students was sampled using simple random sampling. All met the inclusion criteria. A self-administered semi-structured questionnaire was used for data collection. Data was analyzed using statistical package for social sciences (SPSS) version 22. Data was presented using tables.ResultThe study had a 100% response rate. Results showed the prevalence of mild depression amongst the respondents as 58.1%, the prevalence of moderate depression amongst the respondents as 31.1% while the prevalence of severe depression was 10.7%. The study found the prevalence of depression to be higher in older adolescents and females. There was also a significant relationship between satisfaction with academic performance and depression.ConclusionThere was significant level of prevalence of depression among senior secondary school students in Enugu metropolis, notably among the females, older adolescents and those who were not satisfied with their academic performance.RecommendationsDepression should be seen as what it is, a disease and awareness should be carried out to adequately sensitize the involved population on early recognition of signs and symptoms of depression, appropriate support and therapy and subsequent rehabilitation of depressed individuals.
A lightweight data-driven spiking neural network model ofDrosophilaolfactory nervous system with dedicated hardware support
Authors: Nanami Takuya , Yamada Daichi , Someya Makoto , Hige Toshihide , Kazama Hokto , Kohno Takashi 
Published: October 2023

AbstractData-driven spiking neural network (SNN) models are vital for understanding the brain’s information processing at the cellular and synaptic level. While extensive research has focused on developing data-driven SNN models for mammalian brains, their complexity poses challenges in achieving precision. Network topology often relies on statistical inference, and the functions of specific brain regions and supporting neuronal activities remain unclear. Additionally, these models demand significant computational resources. Here, we propose a lightweight data-driven SNN model that strikes a balance between simplicity and reproducibility. We target theDrosophilaolfactory nervous system, extracting its network topology from connectome data. The model implemented on an entry-level field-programmable gate array successfully reproduced the functions and characteristic spiking activities of different neuron types. Our approach thus provides a foundation for constructing lightweightin silicomodels that are critical for investigating the brain’s information processing mechanisms at the cellular and synaptic level through an analysis-by-construction approach and applicable to edge artificial intelligence (AI) systems.
Nanobodies against SARS-CoV-2 non-structural protein Nsp9 inhibit viral replication by targeting innate immunity
Authors: Venit Tomas , Blavier Jeremy , Maseko Sibusiso B. , Shu Sam , Espada Lilia , Breunig Christopher , Holthoff Hans-Peter , Desbordes Sabrina C. , Lohse Martin , Esposito Gennaro , Twizere Jean-Claude , Percipalle Piergiorgio 
Published: October 2023

AbstractNanobodies are emerging as critical tools for drug design. Several have been recently created to serve as inhibitors of SARS-Cov-2 entry in the host cell by targeting surface-exposed Spike protein. However, due to the high frequency of mutations that affect Spike, these nanobodies may not target it to their full potential and as a consequence, inhibition of viral entry may not be efficient. Here we have established a pipeline that instead targets highly conserved viral proteins that are made only after viral entry into the host cell when the SARS-Cov-2 RNA-based genome is translated. As proof of principle, we designed nanobodies against the SARS-CoV-2 non-structural protein Nsp9, required for viral genome replication. To find out if this strategy efficiently blocks viral replication, one of these anti-Nsp9 nanobodies, 2NSP23, previously characterized using immunoassays and NMR spectroscopy for epitope mapping, was encapsulated into lipid nanoparticles (LNP) as mRNA. We show that this nanobody, hereby referred to as LNP-mRNA- 2NSP23, is internalized and translated in HEK293 cells. We next infected HEK293-ACE2 cells with multiple SARS-CoV-2 variants and subjected them to LNP-mRNA-2NSP23 treatment. Analysis of total RNA isolated from infected cells treated or untreated with LNP-mRNA-2NSP23 using qPCR and RNA deep sequencing shows that the LNP-mRNA-2NSP23 nanobody protects HEK293-ACE2 cells and suppresses replication of several SARS-CoV-2 variants. These observations indicate that following translation, the nanobody 2NSP23 inhibits viral replication by targeting Nsp9 in living cells. We speculate that LNP-mRNA-2NSP23 may be translated into an innovative technology to generate novel antiviral drugs highly efficient across coronaviruses.
Rho GTPase signaling and mDia facilitate endocytosis via presynaptic actin
Authors: Oevel Kristine , Hohensee Svea , Kumar Atul , Rosas-Brugada Irving , Bartolini Francesca , Soykan Tolga , Haucke Volker 
Published: October 2023

ABSTRACTNeurotransmission at synapses is mediated by the fusion and subsequent endocytosis of synaptic vesicle membranes. Actin has been suggested to be required for presynaptic endocytosis but the mechanisms that control actin polymerization and its mode of action within presynaptic nerve terminals remain poorly understood. We combine optical recordings of presynaptic membrane dynamics and ultrastructural analysis with genetic and pharmacological manipulations to demonstrate that presynaptic endocytosis is controlled by actin regulatory diaphanous-related formins mDia1/3 and Rho family GTPase signaling. We show that impaired presynaptic actin assembly in the near absence of mDia1/3 and reduced RhoA activity is partly compensated by hyperactivation of Rac1. Inhibition of Rac1 signaling further aggravates impaired presynaptic endocytosis elicited by loss of mDia1/3. Our data suggest that interdependent mDia1/3-Rho and Rac1 signaling pathways cooperatively act to facilitate synaptic vesicle endocytosis by controlling presynaptic F-actin.
The RNA binding protein, HNRNPA2B1, regulates IFNG signaling in macrophages
Authors: Salih Mays Mohammed , Weindel Chi G , Malekos Eric , Sudek Lisa , Katzman Sol , Mabry Cory J , Coleman Aja K , Azam Sikandar , Watson Robert , Patrick Kristin , Carpenter Susan 
Published: October 2023

SummaryHeterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) is a well known RNA binding protein but the mechanisms by which it contributes to innate immune gene regulation are poorly understood. Here we report that HNRNPA2B1 functions in macrophages to regulate IFNG (IFN-γ) signaling through alternative splicing of the IFNG receptor. Specific deletion of HNRNPA2B1 in macrophages resulted in altered cytokine responses in both an endotoxic shock model and followingSalmonellainfection. Interestingly, while HNRNPA2B1 can function as a viability gene, we observed increased macrophage and neutrophil numbers in the KO mice following LPS induced endotoxic shock. We also discovered that HNRNPA2B1 restricts replication ofSalmonella enterica in vivo. Mechanistically, loss of HNRNPA2B1 resulted in an increase in NGO transcripts, which lack a start codon, of the IFNG receptor (Ifngr) leading to lower expression of the receptor at the cell surface impacting the downstream IFNG signaling cascade. Collectively, our data highlight an important role for HNRNPA2B1 in regulating IFNG signaling and restricting intracellular bacterial pathogens in macrophages.
Multiparameter flow cytometric detection and analysis of rare cellsin in vivomodels of cancer metastasis
Authors: Mallin Mikaela M , Pienta Kenneth J. , Amend Sarah R. 
Published: October 2023

AbstractRapid and reliable circulating tumor cell (CTC) and disseminated tumor cell (DTC) detection forms a major underpinning of rigorousin vivometastasis research. While many cancer cells initiate metastasis, very few can complete it. Clinical data evidences that each successive step of metastatic cascade presents increasing barriers to metastatic success, limiting the number of successful metastatic cells to fewer than 1 in 1,500,000,000. As such, it is critical to employ metastasis research approaches that allow scientists to discern which step(s) of the cascade present metastatic barriers to their model systems, and in which steps their model systems might display competency. Here, we present a novel flow-cytometry based method that allows for the simultaneous comparison of multiple steps of the cascade within one model system via the co-identification of CTC and DTCs from single animals. This approach is not only highly reliable and reproducible, but also broadly applicable and highly adaptable to a wide range of scientific inquiries.
Activation of automethylated PRC2 by dimerization on chromatin
Authors: Sauer Paul V. , Pavlenko Egor , Cookis Trinity , Zirden Linda C. , Renn Juliane , Singhal Ankush , Hunold Pascal , Hoehne Michaela N. , van Ray Olivia , Hänsel-Hertsch Robert , Sanbonmatsu Karissa Y. , Nogales Eva , Poepsel Simon 
Published: October 2023

SummaryPolycomb Repressive Complex 2 (PRC2) is an epigenetic regulator that trimethylates lysine 27 of histone 3 (H3K27me3) and is essential for embryonic development and cellular differentiation. H3K27me3 is associated with transcriptionally repressed chromatin and is established when PRC2 is allosterically activated upon methyl-lysine binding by the regulatory subunit EED. Automethylation of the catalytic subunit EZH2 stimulates its activity by an unknown mechanism. Here, we show that PRC2 forms a dimer on chromatin in which an inactive, automethylated PRC2 protomer is the allosteric activator of a second PRC2 that is poised to methylate H3 of a substrate nucleosome. Functional assays support our model of allosterictrans-autoactivation via EED, suggesting a novel mechanism mediating context- dependent activation of PRC2. Our work showcases the molecular mechanism of auto- modification coupled dimerization in the regulation of chromatin modifying complexes.
Prevalence of Autoimmune Diseases in Functional Neurological Disorder: Influence of Psychiatric Comorbidities and Biological Sex
Authors: Joseph Anna , Baslet Gaston , Neal Mary A O’ , Polich Ginger R , Gonsalvez Irene , Christoforou Andrea N , Dworetzky Barbara A , Spagnolo Primavera A 
Published: October 2023

AbstractBackgroundFunctional neurological disorder (FND) is a common and disabling neuropsychiatric condition, which disproportionally affects women compared to men. While the etiopathogenesis of this disorder remains elusive, immune dysregulation is emerging as one potential mechanism.AimTo begin to understand the role of immune dysfunction in FND, we assessed the prevalence of several common autoimmune diseases (ADs) in a large cohort of patients with FND and examined the influence of psychiatric comorbidities and biological sex.MethodsUsing a large biorepository database (Mass General Brigham Biobank), we obtained demographic and clinical data of a cohort of 643 patients diagnosed with FND between January 2015 and December 2021. The proportion of ADs was calculated overall, by sex and by presence of psychiatric comorbidities.ResultsThe overall prevalence of ADs in our sample was 41.9%, with connective tissue and autoimmune endocrine diseases being the most commonly observed ADs. Among patients with FND and ADs, 27.7% had ≥2 ADs and 8% met criteria for multiple autoimmune syndrome. Rates of ADs were significantly higher in subjects with comorbid major depressive disorder and post-traumatic stress disorder (p=□0.02). Women represented the largest proportion of patients with concurrent ADs, both in the overall sample and in the subgroups of interest (p’s□<□0.05).ConclusionsThis study is unique in providing evidence of an association between FND and ADs. Future studies are needed to investigate the mechanisms underlying this association and to understand whether FND is characterized by distinct dysregulations in immune response.
Diversity, Equity, and Inclusion or Bigotry, Inequity, and Exclusion? Applicant Perceptions of Obstetrics and Gynecology Residency Programs
Authors: Hale Corinne M. , Cowley Elise S. , Hebgen Shanaya , Spencer Ryan , Jacques Laura 
Published: October 2023

AbstractIntroductionResidency applicants often evidence of Obstetrics and Gynecology (ObGyn) residency programs’ commitments to diversity, equity, and inclusion. Online peer-to-peer discussions suggest applicants evaluate program commitment to diversity, equity, and inclusion through formal and informal channels and share their insights and experiences to help each other form opinions about program culture.MethodsThe study team examined applicant descriptions of ObGyn residency programs using qualitative data collected from a public resource available on the social media platform, Reddit. Using an inductive approach, the team analyzed anonymous comments in a shared document called “2020-2021 OB GYN Residency Applicant Spreadsheet” housed within Reddit to better understand applicants’ experiences with and perceptions of US ObGyn residency programs. Codes were collectively determined and assigned to 731 unique comments; this paper focuses on the codes directly and indirectly related to diversity, equity, and inclusion as well as racism, discrimination, and bigotry.ResultsWe found that applicants used visual, verbal, and behavioral cues to analyze ObGyn residency programs. Students primarily used perceptions gained in program interview days, social events, faculty social media profiles, and program websites to decipher programs’ values and internal commitment to pursuing diversity, equity, and inclusion.ConclusionsThis study emphasizes the value applicants place on residency programs’ commitments to DEI. Programs that can clearly demonstrate their dedication to DEI principles are more likely to attract a diverse applicant pool that will become the future medical workforce. Programs can provide informative context related to DEI undertakings, reducing the risk that applicants will draw erroneous conclusions from partial information.
Genetically refactoredAgrobacterium-mediated transformation
Authors: Thompson Mitchell G. , Kirkpatrick Liam D. , Geiselman Gina M. , Waldburger Lucas M. , Pearson Allison N. , Szarzanowicz Matthew , Vuu Khanh M. , Markel Kasey , Hummel Niklas F. C. , Suazo Dennis D. , Tahmin Claudine , Cui Ruoming , Liu Shuying , Cevallos Jasmine , Pannu Hamreet , Liu Di , Gin Jennifer W. , Chen Yan , Petzold Christopher J. , Gladden John M. , Keasling Jay D. , Chang Jeff H. , Weisberg Alexandra J. , Shih Patrick M. 
Published: October 2023

AbstractMembers ofAgrobacteriumare costly plant pathogens while also essential tools for plant transformation. ThoughAgrobacterium-mediated transformation (AMT) has been heavily studied, its polygenic nature and its complex transcriptional regulation make identifying the genetic basis of transformational efficiency difficult through traditional genetic and bioinformatic approaches. Here we use a bottom-up synthetic approach to systematically refactor the tumor-inducing plasmid, wherein the majority of AMT machine components are encoded, into a minimal set of genes capable of plant and fungal transformation that is both controllable and orthogonal to its environment. We demonstrate that engineered vectors can be transferred to new heterologous bacteria, enabling them to transform plants. Our reductionist approach demonstrates how bottom-up engineering can be used to dissect and elucidate the genetic underpinnings of complex biological traits, and may lead to the development of strains of bacteria more capable of transforming recalcitrant plant species of societal importance.
Human pluripotent stem cell-derived hepatocyte-like cells for hepatitis D virus studies
Authors: Chi Huanting , Qu Bingqian , Prawira Angga , Maurer Lars , Hu Jungen , Fu Rebecca M. , Lempp Florian A. , Zhang Zhenfeng , Grimm Dirk , Wu Xianfang , Urban Stephan , Dao Thi Viet Loan 
Published: October 2023

AbstractCurrent culture systems available for studying hepatitis D virus (HDV) are suboptimal. In this study, we demonstrate that hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) are fully permissive to HDV infection across various tested genotypes. When co- infected with the helper hepatitis B virus (HBV) or transduced to express the HBV envelope protein HBsAg, HLCs effectively secrete infectious progeny virions. We also show that HLCs expressing HBsAg support extracellular spread of HDV, thus providing a valuable platform for testing available anti-HDV regimens. By challenging the cells along the differentiation with HDV infection, we have identified CD63 as a potential HDV/HBV co-entry factor, which was rate-limiting HDV infection in immature hepatocytes. Given their renewable source and the potential to derive hPSCs from individual patients, we propose HLCs as a promising model for investigating HDV biology. Our findings offer new insights into HDV infection and expand the repertoire of research tools available for the development of therapeutic interventions.TeaserA human stem cell-derived hepatocyte culture model for hepatitis D virus studies
Enhancing a multipurpose artificial urine for culture and gene expression studies of uropathogenicEscherichia colistrains
Authors: Rimbi Patricia T. , O’Boyle Nicky , Douce Gillian R. , Pizza Mariagrazia , Rosini Roberto , Roe Andrew J. 
Published: October 2023

AbstractUropathogenicEscherichia coli(UPEC) are the most common cause of urinary tract infections, which pose a great burden on global health and the economy through morbidity, mortality, healthcare costs and loss of productivity. Pooled human urine can be used as a growth medium forin vitrostudies, however even if the same donors are used, composition can vary depending largely on diet and fluid intake. There have been a number of artificial urine formulae used as alternatives to pooled human urine. However, we observed that a recently reported multipurpose artificial urine was unable to support the growth of prototypic UPEC strains suggesting it lacked key metabolites. We therefore used liquid chromatography mass spectrometry to identify and adjust the metabolic profile of multipurpose artificial urine closer to that of pooled human urine. Modification in this way facilitated growth of UPEC strains with growth rates similar to those obtained in pooled human urine. Transcriptomic analysis of UPEC strains cultured in enhanced artificial urine and pooled human urine showed that the gene expression profiles are similar, with less than 7% of genes differentially expressed between the two conditions. The data support this enhanced artificial urine as a robust media to study aspects of UPEC physiologyin vitro.
Fucose is an essential feature in cryoprotective polysaccharides
Authors: Guerreiro B. M. , Concórdio-Reis P. , Pericão H. , Martins F. , Moppert X. , Guézennec J. , Lima J.C. , Silva J.C. , Freitas F. 
Published: October 2023

AbstractBiological cryopreservation often involves using a cryoprotective agent (CPA) to mitigate lethal physical stressors cells endure during freezing and thawing, but effective CPA concentrations are cytotoxic. Hence, natural polysaccharides have been studied as biocompatible alternatives. Our current investigation studied 26 natural polysaccharides as potential CPA, probing correlations between post-thaw metabolic viability (PTV) of cryopreserved Vero cells and monomeric composition. The best performing cryoprotective polysaccharides contained significant fucose amounts, resulting in average PTV 2.8-fold (up to 3.1-fold) compared to 0.8-fold and 2.2-fold for all non-cryoprotective and cryoprotective polysaccharides, respectively, outperforming the optimized commercial CryoStor™ CS5 formulation (2.6-fold). Stoichiometrically, a balance between fucose (18–35.7 mol%), uronic acids (UA) (13.5–26 mol%) and high molecular weight (MW > 1 MDa) generated optimal PTV. To deconvolute multiple variable effects, principal component analysis (PCA) coupled toK-means clustering was performed. Two major mechanisms of action explained PTV variability: a charge-dependent effect of contrasting charged uronic acid and neutral monomer compositions, and a MW-scaled charge-independent mechanism exclusively attributed to fucose. Ultimately, our research showed the critical role neutral fucose plays in enhancing cellular cryopreservation outcomes, disputing previous assumptions of polyanionicity being the sole governing predictor of cryoprotection, highlighting the potential of fucose-rich polyanionic polysaccharides.