Borrebach0834

Topoisomerase 1 (Top1) removes transcription-associated helical stress to suppress G4-formation and its induced recombination at genomic loci containing guanine-run containing sequences. Interestingly, Top1 binds tightly to G4 structures, and its inhibition or depletion can cause elevated instability at these genomic loci. Top1 is targeted by the widely used anti-cancer chemotherapeutic camptothecin (CPT) and its derivatives, which stabilize Top1 covalently attached on a DNA nick and prevent the re-ligation step. Here we investigated how CPT-resistance conferring Top1 mutants, which emerge in cancer patients and cells treated with CPT, affect G4-induced genomic instability in S. cerevisiae. We found that Top1 mutants form stable complexes with G4 DNA and that expression of Top1 cleavage-defective mutants but not a DNA-binding-defective mutant lead to significantly elevated instability at a G4-forming genomic locus. Elevated recombination rates were partly suppressed by their proteolytic removal by SPRTN homolog Wss1 SUMO-dependent metalloprotease in vivo. Furthermore, interaction between G4-DNA binding protein Nsr1, a homolog to clinically-relevant human nucleolin, and Top1 mutants lead to a synergistic increase in G4-associated recombination. These results in the yeast system are strengthened by our cancer genome data analyses showing that functionally detrimental mutations in Top1 correlate with an enrichment of mutations at G4 motifs. Our collective experimental and computational findings point to cooperative binding of Top1 cleavage-defective mutants and Nsr1 as promoting DNA replication blockage and exacerbating genomic instability at G4-motifs, thus complicating patient treatment.Missing hierarchical is-a relations and missing concepts are common quality issues in biomedical ontologies. Non-lattice subgraphs have been extensively studied for automatically identifying missing is-a relations in biomedical ontologies like SNOMED CT. However, little is known about non-lattice subgraphs' capability to uncover new or missing concepts in biomedical ontologies. In this work, we investigate a lexical-based intersection approach based on non-lattice subgraphs to identify potential missing concepts in SNOMED CT. We first construct lexical features of concepts using their fully specified names. Then we generate hierarchically unrelated concept pairs in non-lattice subgraphs as the candidates to derive new concepts. For each candidate pair of concepts, we conduct an order-preserving intersection based on the two concepts' lexical features, with the intersection result serving as the potential new concept name suggested. We further perform automatic validation through terminologies in the Unified Medical Language System (UMLS) and literature in PubMed. Applying this approach to the March 2021 release of SNOMED CT US Edition, we obtained 7,702 potential missing concepts, among which 1,288 were validated through UMLS and 1,309 were validated through PubMed. The results showed that non-lattice subgraphs have the potential to facilitate suggestion of new concepts for SNOMED CT.The context in which drinking occurs is a critical but relatively understudied factor in alcohol use disorder (AUD) etiology. Selleck Guggulsterone E&Z In this article, I offer a social-contextual framework for examining AUD risk by reviewing studies on the unique antecedents and deleterious consequences of social versus solitary alcohol use in adolescents and young adults. Specifically, I provide evidence of distinct emotion regulatory functions across settings, with social drinking linked to enhancing positive emotions and social experiences and solitary drinking linked to coping with negative emotions. I end by considering the conceptual, methodological, and clinical implications of this social-contextual account of AUD risk.

Middle-aged and older individuals with spinal cord injury (SCI) often require long-term care even after receiving rehabilitation treatment, making it difficult for them to return home. We retrospectively investigated our active rehabilitation treatment for patients with SCI.

Included in this case series were ten patients with SCI who were admitted to our general hospital (located in the southern part of Wakayama Prefecture) and who underwent active rehabilitation treatment. The participants were investigated retrospectively by access to electronic medical records. The Barthel index scores for discharged patients were determined at an outpatient clinic, and the community phase of rehabilitation management was recorded. The average age of the 10 patients was 67.4 ± 13.4 years, and the average period from onset to transfer to our hospital was 102.6 ± 69.9 days. The Barthel index scores significantly improved from 39.0 ± 30.9 at admission to 65.0 ± 28.2 at discharge (P<0.05). Among the seven patients who were discharged to their homes, six had cervical SCI. Some patients with American Spinal Injury Association impairment scale grades A and B at admission could be discharged home, and their Barthel index scores were maintained after discharge.

Even in a remote rural hospital, the activities of daily living of patients with SCI improved, and seven of the ten patients were discharged home. The activities of daily living of the discharged patients were maintained. To achieve these results, active rehabilitation treatment conducted by rehabilitation specialists is important.

Even in a remote rural hospital, the activities of daily living of patients with SCI improved, and seven of the ten patients were discharged home. The activities of daily living of the discharged patients were maintained. To achieve these results, active rehabilitation treatment conducted by rehabilitation specialists is important.This paper uses spatial statistical techniques to reflect on geographies of COVID-19 infections in metropolitan Melbourne. We argue that the evolution of the COVID-19 pandemic, which has become widespread since early 2020 in Melbourne, typically proceeds through multiple built environment attributes - diversity, destination accessibility, distance to transit, design, and density. The spread of the contagion is institutionalised within local communities and postcodes, and reshapes movement practices, discourses, and structures of administrative politics. We demonstrate how a focus on spatial patterns of the built environment can inform scholarship on the spread of infections associated with COVID-19 pandemic and geographies of infections more broadly, by highlighting the consistency of built environment influences on COVID-19 infections across three waves of outbreaks. A focus on the built environment influence seeks to enact visions of the future as new variants emerge, illustrating the importance of understanding geographies of infections as global cities adapt to 'COVID-normal' living. We argue that understanding geographies of infections within cities could be a springboard for pursuing sustainable urban development via inclusive compact, mixed-use development and safe public transport.The COVID-19 pandemic is a global problem that confronted the economy and household food security of many countries. This study aimed to analyze the determinants of a household's food insecurity status in the era of the COVID-19 pandemic in Ethiopia. A panel data of 2,410 households in a six-round High-Frequency Phone Survey were retrieved from the World Bank database. The product of the corresponding pairwise severity weight and household responses to each coping strategy was summed up to get the individual's Coping Strategy Index. The Random Effect Model (REM) for panel data analysis was used to identify factors associated with household-related food insecurity during the COVID-19 pandemic. The descriptive statistics result shows that 18.63% and 11.08% of rural households and 56.55% and 38.13% of urban residents were food secure in the first and sixth rounds, respectively. On the contrary, 3.65% and 3.2% of rural households and 6.8% and 7.18% of urban households experienced severe food insecurity from the first to the sixth round, respectively. Most households have maintained their food security in urban areas than rural residents. However, the number of food secure households was gradually reduced from Round-1 to Round-6. Besides, REM output indicates that access to financial services, farm income, wage employment, income from property, investment, and savings, and NGO assistance negatively affected household's food insecurity. Whereas government support showed a positive association with households' food insecurity. Based on the findings, we recommend that households should adopt the behavior of enhancing and diversifying their sources of income, and the government also emphasize the establishment of national social security services by taking experience from NGOs' emergency response mechanisms.For the Pacific Small Island Developing States (PSIDS), climate change will greatly exacerbate their vulnerability. The PSIDS have a high ranking in the Climate Risk Index and the World Risk Index. Financial losses due to climate-induced disasters, in terms of gross domestic product (GDP), are also high in the Pacific region. While climate risk insurance solutions could play a key role in the efficient distribution of recovery resources, there are many challenges to their successful implementation. Effective climate risk insurance products for the vulnerable sections of these societies are almost non-existent in this part of the world. Among the worst climate-induced disasters to affect the PSIDS are those related to cyclones and floods. These not only adversely impact the welfare of the households affected by these disasters, but they lower the long-term development potential of the countries involved. There is also evidence to suggest that climate-induced disasters are increasing in frequency and intensity over time due to climate change. It is against this background that an inquiry into the necessity for climate risk insurance products in the context of PSIDS should take place. This paper gives a comprehensive review of the literature addressing climate risk insurance as a risk mitigation or climate adaptation tool for managing the climate-induced financial vulnerabilities in the PSIDS. The paper explores the affordability of climate risk insurance, particularly among the vulnerable sections of society, and discusses the challenges of implementing an appropriate climate risk insurance model in the region. Finally, it examines recent climate risk insurance initiatives that have been attempted by multilateral agencies, such as the United Nations Development Programme (UNDP), the United Nations' Pacific Financial Inclusion Practice (UNCDF), Pacific Insurance and Climate Adaptation Programme (PICAP), and respective local governments.Childlessness or infertility among couples has become a global health concern. Due to the rise in infertility, couples are looking for medical supports to attain reproduction. This paper deals with diagnosing infertility among men and the major factor in diagnosing infertility among men is the Sperm Morphology Analysis (SMA). In this manuscript, we explore establishing deep learning frameworks to automate the classification problem in the fertilization of sperm cells. We investigate the performance of multiple state-of-the-art deep neural networks on the MHSMA dataset. The experimental results demonstrate that the deep learning-based framework outperforms human experts on sperm classification in terms of accuracy, throughput and reliability. We further analyse the sperm cell data by visualizing the feature activations of the deep learning models, providing a new perspective to understand the data. Finally, a comprehensive analysis is also demonstrated on the experimental results obtained and attributing them to pertinent reasons.