bluuebunny/crossref_metadata_2025_split huggingface dataset:
De novo protein backbone generation based on diffusion with structured priors and adversarial training
Authors: Liu Yufeng , Chen Linghui , Liu Haiyan 
Published: December 2022

AbstractIn de novo deisgn of protein backbones with deep generative methods, the designability or physical plausibility of the generated backbones needs to be emphasized. Here we report SCUBA-D, a method using denoising diffusion with priors of non-zero means to transform a low quality initial backbone into a high quality backbone. SCUBA-D has been developed by gradually adding new components to a basic denoising diffusion module to improve the physical plausibility of the denoised backbone. It comprises a module that uese one-step denoising to generate prior backbones, followed by a high resolution denoising diffusion module, in which structure diffusion is assisted by the simultaneous diffusion of a language model representation of the amino acid sequence. To ensure high physical plausibility of the denoised output backbone, multiple generative adversarial network (GAN)-style discriminators are used to provide additional losses in training. We have computationally evaluated SCUBA-D by applying structure prediction to amino acid sequences designed on the denoised backbones. The results suggest that SCUBA-D can generate high quality backbones from initial backbones that contain noises of various types or magnitudes, such as initial backbones coarsely sketched to follow certain overall shapes, or initial backbones comprising well-defined functional sites connected by unknown scaffolding regions.
A-ring-fused pyrazoles of dihydrotestosterone targeting prostate cancer cells via the downregulation of the androgen receptor
Authors: Peřina Miroslav , Kiss Márton A. , Mótyán Gergő , Szczyrbová Eva , Eliáš Martin , Študent Vladimír , Kurfurstová Daniela , Kovalová Markéta , Mada Lukáš , Bouchal Jan , Frank Éva , Jorda Radek 
Published: December 2022

AbstractHigh expression of the androgen receptor (AR) and the disruption of its regulation are strongly responsible for the development of prostate cancer (PCa). Therapeutically relevant non-steroidal or steroidal antiandrogens are able to block the AR effect by eliminating AR-mediated signalling. Herein we report the synthesis of novel steroidal pyrazoles derived from the natural sex hormone 5α-dihydrotestosterone (DHT). 2-Ethylidene or 2-(hetero)arylidene derivatives of DHT obtained by regioselective Claisen-Schmidt condensation with acetaldehyde or (hetero)aromatic aldehydes in alkaline ethanol were reacted with monosubstituted hydrazines to give A-ring-fused 1,5-disubstituted pyrazoles as main or exclusive products, depending on the reaction conditions applied. Spontaneous or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ)-induced oxidation of the primarily formed pyrazolines resulted in the desired products in moderate to good yields, while 17-oxidation also occurred by using the Jones reagent as a strong oxidant. Transcriptional activity of the AR in a reporter cell line was examined for all novel compounds, and several previously synthesized similar DHT-based pyrazoles with differently substituted heteroring were also included to obtain information about the structure-activity relationship. Two specific regioisomeric groups of derivatives significantly diminished the transcriptional activity of AR in reporter cell line in 10 μM concentration, and displayed reasonable antiproliferative activity in AR-positive PCa cell lines. Lead compound (3d) was found to be a potent AR antagonist (IC50= 1.18 μM), generally suppressed AR signalling in time and dose dependent manner, moreover, it also led to a sharp decrease in wt-AR protein level probably caused by proteasomal degradation. We confirmed the antiproliferative activity selective for AR-positive PCa cell lines (with GI50in low micromolar ranges), cellular, biochemical and in silico binding of3din AR ligand-binding domain. Moreover, compound3dwas shown to be potent evenex vivoin patient-derived tissues, which highlights the therapeutic potential of A-ring-fused pyrazoles.Table of content graphicHighlightsA-ring-fused pyrazoles of 5α-dihydrotestosterone were introduced as AR modulatorsSAR study of 55 differently substituted derivatives was discussedCompound3dsuppressed the expression of AR targets in prostate cell linesCompound3dcaused AR degradation in time-dependent mannerEx vivo activity of3dwas demonstrated in patient-derived explants
Single-Cell Analysis of 5-ALA Intraoperative Labeling Specificity for Glioblastoma
Authors: Liu Zhouzerui , Mela Angeliki , Furnari Julia , Argenziano Michael G. , Kotidis Corina , Sperring Colin P. , Humala Nelson , Bruce Jeffrey N. , Canoll Peter , Sims Peter A. 
Published: December 2022

AbstractGlioblastoma (GBM) is the most common and aggressive malignant primary brain tumor, and surgical resection is a key part of the standard-of-care. In fluorescence-guided surgery (FGS), fluorophores are used to differentiate tumor tissue from surrounding normal brain. The heme synthesis pathway converts 5-aminolevulinic acid (5-ALA), a fluorogenic substrate used for FGS, to fluorescent protoporphyrin IX (PpIX). The resulting fluorescence is thought to be specific to transformed glioma cells, but this specificity has not been examined at single-cell level. We performed paired single-cell imaging and RNA sequencing of individual cells (SCOPE-seq2) on human GBM surgical specimens with visible PpIX fluorescence from patients who received 5-ALA prior to surgery. SCOPE-seq2 allows us to simultaneously image PpIX fluorescence and unambiguously identify transformed glioma cells from single-cell RNA-seq (scRNA-seq). We observed that 5-ALA treatment results in labeling that is not specific to transformed tumor cells. In cell culture, we further demonstrated that untransformed cells can be labeled by 5-ALA directly or by PpIX secreted from surrounding transformed cells. In acute slice cultures from mouse glioma models, we showed that 5-ALA preferentially labels GBM tumor tissue over non-neoplastic brain tissue, and that this contrast is not due to blood-brain-barrier disruption. Taken together, our findings support the use of 5-ALA as an indicator of GBM tissue, but not as a specific marker of transformed glioma cells.
The Megachilidae (Hymenoptera, Apoidea, Apiformes) of the Democratic Republic of Congo curated at the Royal Museum for Central Africa (RMCA, Belgium)
Authors: Nkulu Alain Tshibungu , Pauly Alain , Dorchin Achik , Vereecken Nicolas J. 
Published: December 2022

AbstractNatural history collections (NHCs) are a cornerstone of entomology, and the conservation of specimens is the essential prerequisite for the development of research into systematics, biogeography, ecology, evolution and other disciplines. Yet, specimens collected during decades of entomological research conducted in less developed countries across Sub-Saharan Africa on pests, beneficial insects and insect biodiversity in general have largely been exported to be permanently preserved in developed countries, primarily in South Africa, Europe and the United States of America.This is particularly true for the Democratic Republic of the Congo’s (DRC) diverse wild bee fauna, which has been investigated throughout the colonial period by visiting or resident entomologists and missionaries who have then transferred their collected material primarily to Belgium as part of a wider legacy of scientific exploration and colonialism. Digitizing NHC is one way to mitigate this current bias, by making samples accessible to researchers from the target post-colonial countries as well as to the wider international scientific community.In this study, we compiled and digitized 6,490 specimens records relevant to 195 wild bee species grouped in 18 genera within the biodiverse family Megachilidae, essentially from the colonial era (i.e., mostly between 1905-1960, with additional records up to 1978), and curated at the Royal Museum for Central Africa (RMCA) in Belgium. We provide a detailed catalogue of all records with updated locality and province names, including 26 species only available as type specimens. We also explore the historical patterns of diversity and distribution across DRC, and we provide a list of the research entomologists involved. This study is an important first step that uses digital technologies to democratize and repatriate important aspects of DRC’s natural heritage of insect biodiversity, to stimulate more contemporary field surveys, as well as to identify and characterize research gaps and biodiversity shortfalls in little-explored regions of Sub-Saharan Africa.
Prediction of vasospasms as complication in ischemic stroke patients receiving anterior circulation endovascular stroke treatment
Authors: Jesser Jessica , Awounvo Sinclair , Vey Johannes A. , Vollherbst Dominik , Hilgenfeld Tim , Chen Min , Schönenberger Silvia , Bendszus Martin , Möhlenbruch Markus A. , Weyland Charlotte S. 
Published: December 2022

AbstractBackground and PurposeVasospasms are a common and dreaded complication of endovascular stroke treatment (EST). There is a lack of understanding of risk factors for periprocedural vasospasms. Here, we aimed to identify prognostic factors for vasospasms in patients with acute ischemic stroke and EST.MethodsRetrospective single-center analysis of patients receiving EST for anterior circulation vessel occlusion between January 2015 and December 2021. Exclusion criteria were intracranial stenting and intraarterial (i.a.) thrombolysis. Study groups were defined as patients developing vasospasms during EST (V+) and patients, who did not (V-). The study groups were compared in univariate analysis. Further, multivariable regression models were developed to predict the patients’ risk for developing vasospasms based on pre-identified potential prognostic factors. Secondary endpoint was clinical outcome as modified Rankin Scale (mRS) difference between pre-stroke mRS and discharge mRS (delta mRS).ResultsIn total, 132 of 1768 patients (7.5 %) developed vasospasms during EST in this study cohort. Patients with vasospasms were younger and had a lower pre-stroke disability (as per mRS). Vasospasms were more likely to occur in ESTs with multiple thrombectomy attempts in total and after several stent retriever maneuvers. Factors with predictive value for developing vasospasms were younger (OR = 0.967, 95%-CI = 0.96 - 0.98) and had a lower pre-stroke mRS (OR = 0.759, 95%-CI = 0.63 - 0.91). The prediction model incorporating patient age, pre-stroke mRS, stent retriever thrombectomy attempts, and total attempts as prognostic factors was found to predict vasospasms with decent accuracy (AUC = 0.714, 95%-CI = 0.709-0.720). V+ patients showed higher delta mRS (median (Q1 - Q3); V-: 2 (1-3) vs. V+: 2(1-4); p = 0.014).ConclusionThis study shows that vasospasms are a common complication in EST affecting younger and previously healthier patients and are more likely after multiple stent retriever thrombectomy attempts. As independent predictors patient age, pre-stroke mRS, thrombectomy maneuvers and stent-retriever attempts predict the occurrence of vasospasms during EST with decent accuracy.
COVID-19 and Health System Response for Management of Diabetes in Bangladesh: A national qualitative study of patients with diabetes and key healthcare professionals/policy makers
Authors: Talukder Shamim Hayder , Islam Tasneem , Salahin Kazi Fayzus , Akter Shahin , Farhana Dina , Sultana Ummay Farihin , Shariful Islam Sheikh Mohammed , Shi Zumin , Hussain Akhtar , Godman Brian , Kurdi Amanj 
Published: December 2022

AbstractBackgroundUncontrolled diabetes can lead to exacerbation of symptoms and life-threatening complications. Consequently, there is a need to explore patient experience regarding the prevention and treatment of diabetic patients amidst the restrictions and lockdown measures in response to COVID-19. The objective of this study was to assess the response of the healthcare system for preventive care and treatment of people with diabetes in Bangladesh during COVID-19, and to analyze the health-seeking behavior of diabetes patients amidst social distancing and lockdown measuresMethodA descriptive qualitative design was used to collect data regarding the ability of people living with diabetes to access medication, laboratory services, and preventative care during the pandemic. The data collection process involved 12 focus group discussions (FGDs) with people living with diabetes, and 30 key informants’ interviews (KIIs) with senior diabetologist, health service managers, leaders of different diabetes-related associations, and policymakers from the local to the national level. The discussion issues were structured around the WHO framework that describes health systems in terms of six “building blocks”. In addition, different treatment guidelines, scientific articles, relevant reports, and 20 well-circulated newspapers were analyzed concerning the treatment of diabetic patients.Results44% of the respondents were aged 55-60 years, with an informed noticeable disruption of essential diabetes care services, intensified by high COVID-19 infection rates. Besides, 78% of the service receiver participants reported not seeing any government-issued public announcements regarding diabetes management on television or newspapers. There are also concerns with the current heath sector.ConclusionsThe study findings highlighted major concerns surrounding the healthcare response to deliver care for patients with diabetes during the pandemic, driven mainly by restricted access to treatment under lockdown measures coupled with a reluctance from health care providers to see patients due to high COVID-19 infection rates arising from concerns with a lack of personal protective equipment. Necessary measures can gradually bring some change in the healthcare system promote healthy lifestyles and adherence to prescribed medicines together with raising awareness about the potential risk factors of diabetes.
Health care workers’ level of adherence to infection prevention and control and its impact on puerperal and neonatal sepsis among delivering women and neonates in Central Tanzania: A protocol for prospective cohort study
Authors: Marandu Laura Edward , Masika Golden 
Published: December 2022

AbstractIntroductionDelivering women and neonates are at a great risk of acquiring infections due to lack of adherence to infection prevention and control (IPC) and low level of immunity and extended exposure to care procedures that can lead to infections. This prospective study aims to assess the level of adherence to IPC among health care workers and its impact on puerperal and neonatal sepsis in Dodoma region.Methods and AnalysisLevel of adherence to IPC is examined cross-sectionally among health care workers (HCWs’) in contact with delivering women and their neonates. Prospective cohort approach is used to assess level of exposure of 294 delivering women and their neonates to poor hygienic practices of HCW through observation checklist. Outcomes including incidence of puerperal and neonatal sepsis are evaluated clinically two days later before discharge. Laboratory culture and sensitivity confirmatory tests of blood samples are done on positive cases. Data analysis for level of adherence to IPC practices, incidence of puerperal and neonatal sepsis as well as relative risk among the exposed women and neonates will be performed.Ethics and DisseminationThe University of Dodoma Research Ethics Committee (UDOM-REC) approved this study (Ref No. MA.84/261/’A’/25). Findings of this study will be published in international peer reviewed journals, disseminated in international conferences, to the participating hospitals, the University of Dodoma and the Tanzanian Ministry of Health for informing practice and policy.Strengths and limitations of this studyBy capturing data from both health care workers and patients using mixed methods approach, the study can examine the impact of health care worker’s infection prevention, and control practice on patient’s outcomes at the same time.Compared to other studies, this study objectively tracks and quantify the risk of infection from all possible points of contact between a health care worker and a client.The study can enable early identification of puerperal or neonatal infection and initiate treatment before discharge Exposure to pre-admission infection long incubation period and manifest at the hospital post-delivery may be difficult to capture and may confound the results without culture and sensitivity.The post-delivery women and their neonates will be followed for two days only to abide to hospital discharge protocol; this will limit the data to early onset of sepsis only.
Targeting MAdCAM-1 can prevent colitic cancer progression by suppressing immune cell infiltration and inflammatory signals
Authors: Ozawa Naoya , Yokobori Takehiko , Osone Katsuya , Bilguun Erkhem-Ochir , Okami Haruka , Shimoda Yuki , Shiraishi Takuya , Okada Takuhisa , Sano Akihiko , Sakai Makoto , Sohda Makoto , Miyazaki Tatsuya , Ide Munenori , Ogawa Hiroomi , Yao Takashi , Oyama Tetunari , Shirabe Ken , Saeki Hiroshi 
Published: December 2022

AbstractChronic inflammation by infiltrating immune cells promotes colitis-associated dysplasia/colitic cancer in ulcerative colitis (UC) via activating inflammatory cytokine signalling (IL-6/p-STAT3 and TNFα/NF-κB). Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a cell adhesion molecule expressed on high endothelial venules that promote immune cell migration from the bloodstream to the gut. MAdCAM-1 targeting strategy is attracting attention as a novel therapeutic option for UC. However, the significance of MAdCAM-1-positive vessels in dysplasia/colitic cancers remains unclear. We conducted immunohistochemistry against MAdCAM-1, and immune cell markers in surgically resected samples from 11 UC patients with dysplasia/colitic cancer and 17 patients with sporadic colorectal cancer (SCRC). Moreover, we used a colitic cancer model, azoxymethane (AOM)/dextran sodium sulphate (DSS) mouse, to evaluate whether anti-MAdCAM-1 blocking antibody can suppress colitic cancer progression. MAdCAM-1-positive vessel number and infiltrating CD8-, CD68-, and CD163-positive immune cell numbers were significantly higher in dysplasia/colitic cancer than in normal mucosa, SCRC, and UC mucosa. In the AOM/DSS mouse model, MAdCAM-1 antibody reduced the tumour number, tumour diameter, number of CD8-, CD68-, and CD163-positive immune cells, and IL-6/p-STAT3 and TNFα/NF-κB expression levels. Targeting MAdCAM-1 could be promising for inflammatory carcinogenesis, and tumour progression by regulating inflammation/immune cell infiltration in patients with UC.Lay summary:MAdCAM-1 targeting strategy can control ulcerative colitis severity, carcinogenesis, and tumour progression by regulating inflammation/immune cell infiltration in patients with ulcerative colitis.
Moving from Total Concentrations to Measures of Harm in Grain Sold at Selected Markets of Southwest Nigeria
Authors: Oshatunberu Modupe Abeke , Oladimeji Adebayo , Henry Sawyerr Olawale , Olaniyan Opasola Afolabi , Raimi Morufu Olalekan 
Published: December 2022

AbstractRegardless of where you live or who you are, food safety is crucial for human health. Pesticide residues are commonly exposed to consumers in Nigeria through their food. What consequences, if any, such chemical pollutants cause to consumer health remain unclear given the presence of pesticide residues in food. To this end, the objective is to determine the concentration of the identified pesticide in grains commonly used by farmers, and which are available directly from the open markets in the Nigerian market. Pesticide residues were quantified through a multiresidue method using a varian 3800/4000 gas chromatograph mass spectrometer was used to analyze pesticide residues. The simultaneous determination of four classes of pesticides: carbamates, organochlorines, organophosphates, and pyrethroids by gas chromatography-mass spectrometry (GC/MS) method using sample preparation on QuEChERS-citrate, was developed and validated. The results frequently showed high inter- and intra-specific contamination, which makes sense given the target market and dietary diversity in the area. This study found that grains purchased from particular markets in southwest Nigeria contained numerous pesticide residues. The MRLs set by the EU or FAO/WHO or both were surpassed by 17 out of the total 27 pesticides reported in this work in at least one grain, despite the fact that there were no published codex MRLs for some pesticide residues in some grains.These residues were dispersed among the four classes of pesticides: carbamates, organochlorines, organophosphates, and pyrethroids. In actuality, 90% of the mainly banned organochlorine pesticides exceeded MRLs. Thus, this study revealed concentration levels of organo-chloride pesticides and organo-phosphate pesticides in grain samples drawn from selected markets in southwest Nigeria. Consumers seeking high-quality food in Nigeria should take note of these facts. Notwithstanding, the small percentage of samples with detectable residues suggests that there is a need to increase the monitoring of pesticides in grains, educate farmers, and raise their awareness of the dangers of unauthorized use of pesticides that are restricted for use in agriculture, which can harm the industry’s reputation as a whole.
Hypergraphs and centrality measures identifying key features in gene expression data
Authors: Barton Samuel , Broad Zoe , Ortiz-Barrientos Daniel , Donovan Diane , Lefevre James 
Published: December 2022

AbstractMultidisciplinary approaches can significantly advance our understanding of complex systems. For instance, gene co-expression networks align prior knowledge of biological systems with studies in graph theory, emphasising pairwise gene to gene interactions. In this paper, we extend these ideas, promoting hypergraphs as an investigative tool for studying multi-way interactions in gene expression data. Additional freedoms are achieved by representing individual genes with hyperedges, and simultaneous testing each gene against many features/vertices. Further gene/hyperedge interactions can be captured and explored using the line graph representations, a techniques that also reduces the complexity of dense hypergraphs. Such an approach provides access to graph centrality measures, which in turn identify salient features within a data set, for instance dominant or hub-like hyperedges leading to key knowledge on gene expression. The validity of this approach is established through the study of gene expression data for the plant speciesSenecio lautusand results will be interpreted within this biological setting.
A sigmoid curve analysis method for pharmacological experimental results
Authors: Niu Qingxia , Zhao Chengyan 
Published: December 2022

AbstractSigmoid curve (S-curve) is a basic exhibition form of dose-effect relationship in drug reaction. To analyze S-curve is an important method to well-understand drug reaction performance (DRP). The present study introduced an S-curve analysis method for pharmacological experiment results (PERs), the core of which was to solve the problem of the linear fitting of S-curve equation (S-Eq). The linear fitting Eqs of S-Eq were established with 100% fitness. Meanwhile, mathematical and pharmacological meaning of S-curve constants, ED50and maximum effect (ymax) were clarified. The same group of experimental data was analyzed by the present method and four traditional analysis methods. The result indicates that the experimental parameters and their values displaying DRP got by different methods are different. The S-curve analysis method is closer to real drug reaction law.