syedzayyan/paper_mill_benchmark huggingface dataset:
Prevention of indigenous malaria cases by strengthening migration surveillance at village level in Purbalingga Regency, Central Java Province, Indonesia.

Purbalingga regency had achieved zero indigenous malaria cases in april 2016, 3 years before the targeted deadline for elimination.Currently, the biggest threat to elimination efforts is the risk of local malaria reintroduction due to imported cases in the receptive areas.The aim of this study was to describe the implementation of village level migration surveillance and identify the areas for improvement in it.We performed the study in four malaria-free focus villages in purbalingga regency, i.e., pengadegan, sidareja, panusupan, and rembang, from march to october 2019.A total of 108 participants were involved in the processes.Data on malaria vector species, community mobility from malaria-endemic areas, and implementation of malaria migration surveillance (mms) were collected.We use descriptive analysis for quantitative data and thematic content for qualitative data.Socialization of migration surveillance in pengadegan and sidareja villages has been carried out to the wider community, whereas in panusupan and tunjungmuli villages, it is still limited to neighbors.Communities in pengadegan and sidareja villages have participated in reporting the arrivals of migrant workers, and the village malaria interpreter conducts blood tests on all migrants.Community participation in reporting migrant workers arriving in panusupan and tunjungmuli villages is still low.Recording of migrant data reporting has been carried out by mms officers, but malaria checks are only carried out before eid al-fitr to prevent importation of malaria cases.The program needs to strengthen the community mobilization and case-finding efforts.

Journal: WHO South-East Asia journal of public health (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Efficacy and Safety of Posterior Long-Segment Fixation Versus Posterior Short-Segment Fixation for Kummell Disease: A Meta-Analysis.

Posterior short-segment fixation (ssf) and long-segment fixation (lsf) are two methods for the treatment of kummell disease, but the safety and effectiveness of these two surgical methods still lack adequate medical evidence.This study aimed to evaluate the two methods.Methods database searches for randomized controlled trials, case-control studies, and cohort studies of posterior ssf and posterior lsf in the treatment of kummell disease were performed.After the document quality was evaluated with the newcastle-ottawa quality assessment scale, a meta-analysis was carried out.Results meta-analysis revealed that the operation time and intraoperative blood loss in the lsf group were higher than those in the ssf group [md = -18.17, 95% ci (-30.31, -6.03), z = 2.93,p= .003; md = -82.07, 95% ci (-106.91, -57.24], z = 6.48,p .05).Conclusion ssf and lsf are effective and safe for the treatment of kummell disease.Ssf can reduce the operation time and intraoperative bleeding; lsf can better maintain the long-term stability of kyphosis.The methods should be evaluated by clinicians according to the individual situation of the patients.

Journal: Geriatric orthopaedic surgery & rehabilitation (2022)
Publication types: Journal Article;Review
Binding specificity of type three secretion system effector NleH2 to multi-cargo chaperone CesT and their phosphorylation.

Gram-negative pathogens like enteropathogenic escherichia coli (epec) utilize the type three secretion system (t3ss) to translocate various effector proteins that are needed to "hijack" the host system for pathogenic survival.Specialized t3ss chaperones inside bacterial cells stabilize these effector proteins and facilitate their translocation.Ces t is a unique multi-cargo chaperone that interacts with and translocates ~10 different effector proteins.Here, we report the specific interaction between ces t and its key effector, nle h2, and explore the potential role of nle h2 as a kinase for ces t phosphorylation.First, we identified the chaperone-binding domain (cbd; 19-97aa) of nle h2, and mapped the specific interaction sites for both ces t and nle h2.The n- and c-terminal residues of the cbd interact with the dimeric interface of ces t.Further, we compared the ces t binding to nle h2, to that of another key effector tir and with the global carbon regulator csr a.Notably, the effectors have the binding regions at the β-sheet core and dimer interface of ces t, whereas the csr a regulator interacts predominantly through the c-terminal region, which is found ~17 å away from the effectors-binding sites.Next, we showed that nle h2 remains an active kinase even as a complex with ces t and is responsible for its autophosphorylation as well as phosphorylation of ces t at tyr153.Collectively, our findings enhance the understanding of the role of multi-cargo chaperone ces t in orchestrating effector translocation through t3ss.

Journal: Protein science : a publication of the Protein Society (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
In silicoassessment and sonochemical synthesis of 2-alkynyl 3-chloropyrazines as prospective ligands for SARS-CoV-2.

The recent global pandemic caused by covid-19 has triggered an intense effort worldwide towards the development of an effective cure for this disease.In our effort we have explored the 2-alkynyl substituted 3-chloropyrazine framework as a potential template for the design of molecules for this purpose.Our strategy was supported by thein silicostudies of representative compounds to assess their binding affinitiesviadocking into the n-terminal rna-binding domain (ntd) of n-protein of sars-co v-2.Thus we created a small library of molecules based on the aforementioned templateviaan environmentally safer method that involved the rapid synthesis of 2-alkynyl 3-chloropyrazine derivatives under cu-catalysis assisted by ultrasound.The reactions proceededviathe coupling of 2,3-dichloropyrazine with commercially available terminal alkynes in the presence of cu i, pph3and k2co3in peg-400.Further molecular modelling studies helped in establishing a virtual sar (structure activity relationship) within the series and identification of three potential hits.The desirable adme was also predicted for these three molecules suggesting their prospective medicinal value.

Journal: Journal of molecular structure (2021)
Publication types: Journal Article
Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial.

Sunitinib, a multitargeted tyrosine kinase inhibitor (tki), is approved for advanced gastrointestinal stromal tumor (gist) after imatinib failure.Ripretinib is a switch-control tki approved for advanced gist after prior treatment with three or more tkis, including imatinib.We compared efficacy and safety of ripretinib versus sunitinib in patients with advanced gist who were previously treated with imatinib (intrigue, clinical trials.gov identifier: nct03673501).Patients and methods random assignment was 1:1 to once-daily ripretinib 150 mg or once-daily sunitinib 50 mg (4 weeks on/2 weeks off) and stratified by kit/platelet-derived growth factor αmutation and imatinib intolerance.The primary end point was progression-free survival (pfs) by independent radiologic review using modified response evaluation criteria in solid tumors version 1.1.Secondary end points included objective response rate by independent radiologic review, safety, and patient-reported outcome measures.Results overall, 453 patients were randomly assigned to ripretinib (intention-to-treat [itt], n = 226;kitexon 11 itt, n = 163) or sunitinib (itt, n = 227;kitexon 11 itt, n = 164).Median pfs for ripretinib and sunitinib (kitexon 11 itt) was 8.3 and 7.0 months, respectively (hazard ratio, 0.88; 95% ci, 0.66 to 1.16;p= .36); median pfs (itt) was 8.0 and 8.3 months, respectively (hazard ratio, 1.05; 95% ci, 0.82 to 1.33; nominal p= .72).Neither was statistically significant.Objective response rate was higher for ripretinib versus sunitinib in the kitexon 11 itt population (23.9%v14.6%, nominal p= .03).Ripretinib was associated with a more favorable safety profile, fewer grade 3/4 treatment-emergent adverse events (41.3%v65.6%, nominal p< .0001), and better scores on patient-reported outcome measures of tolerability.Conclusion ripretinib was not superior to sunitinib in terms of pfs.However, meaningful clinical activity, fewer grade 3/4 treatment-emergent adverse events, and improved tolerability were observed with ripretinib.

Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2022)
Publication types: Randomized Controlled Trial;Clinical Trial, Phase III;Journal Article;Research Support, Non-U.S. Gov't
The transgenic chicken derived anti-CD20 monoclonal antibodies exhibits greater anti-cancer therapeutic potential with enhanced Fc effector functions.

Modern genetic techniques, enable the use of animal bioreactor systems for the production and functional enhancement of anti-cancer antibodies.Chicken is the most efficient animal bioreactor for the production of anti-cancer antibodies because of its relatively short generation time, plentiful reproductive capacity, and daily deposition in the egg white.Although several studies have focused on the production of anti-cancer antibodies in egg white, in-depth studies of the biological activity and physiological characteristics of transgenic chicken-derived anti-cancer antibodies have not been fully carried out.Here, we report the production of an anti-cancer monoclonal antibody against the cd20 protein from egg whites of transgenic hens, and validated the bio-functional activity of the protein in b-lymphoma and b-lymphoblast cells.Quantitative analysis showed that deposition of the chickenised cd20 monoclonal antibody (c cd20 m ab) from transgenic chickens increased in successive generations and with increasing transgene copy number.Ultra-performance liquid chromatography (uplc) tandem mass spectrometry (lc/ms/ms) analysis showed that the c cd20 m ab exhibited 14 n-glycan patterns with high-mannose, afucosylation and terminal galactosylation.The c cd20 m ab did not exhibit significantly improved fab-binding affinity, but showed markedly enhanced fc-related functions, including complement-dependent cytotoxicity (cdc) and antibody-dependent cellular cytotoxicity (adcc) compared to commercial rituximab, a chimeric m ab against cd20.Our results suggest that the transgenic chicken bioreactor is an efficient system for producing anti-cancer therapeutic antibodies with enhanced fc effector functions.

Journal: Biomaterials (2018)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Connectome mapping with edge density imaging differentiates pediatric mild traumatic brain injury from typically developing controls: proof of concept.

Although acute neurologic impairment might be transient, other long-term effects can be observed with mild traumatic brain injury.However, when pediatric patients with mild traumatic brain injury present for medical care, conventional imaging with ct and mr imaging often does not reveal abnormalities.Objective to determine whether edge density imaging can separate pediatric mild traumatic brain injury from typically developing controls.Materials and methods subjects were recruited as part of the "therapeutic resources for attention improvement using neuroimaging in traumatic brain injury" (train-tbi) study.We included 24 adolescents (χ=14.1 years of age, σ=1.6 years, range 10-16 years), 14 with mild traumatic brain injury (tbi) and 10 typically developing controls.Neurocognitive assessments included the pediatric version of the california verbal learning test (cvlt) and the attention network task (ant).Diffusion mr imaging was acquired on a 3-tesla (t) scanner.Edge density images were computed utilizing fiber tractography.Principal component analysis (pca) and support vector machines (svm) were used in an exploratory analysis to separate mild tbi and control groups.The diagnostic accuracy of edge density imaging, neurocognitive tests, and fractional anisotropy (fa) from diffusion tensor imaging (dti) was computed with two-sample t-tests and receiver operating characteristic (roc) metrics.Results support vector machine-principal component analysis of edge density imaging maps identified three white matter regions distinguishing pediatric mild tbi from controls.The bilateral tapetum, sagittal stratum, and callosal splenium identified mild tbi subjects with sensitivity of 79% and specificity of 100%.Accuracy from the area under the roc curve (auc) was 94%.Neurocognitive testing provided an auc of 61% (cvlt) and 71% (ant).Fractional anisotropy yielded an auc of 48%.Conclusion in this proof-of-concept study, we show that edge density imaging is a new form of connectome mapping that provides better diagnostic delineation between pediatric mild tbi and healthy controls than dti or neurocognitive assessments of memory or attention.

Journal: Pediatric radiology (2020)
Publication types: Journal Article
snoDB: an interactive database of human snoRNA sequences, abundance and interactions.

Small nucleolar rnas (sno rnas) are an abundant type of non-coding rna with conserved functions in all known eukaryotes.Classified into two main families, the box c/d and h/aca sno rnas, they enact their most well characterized role of guiding site specific modifications in ribosomal rna, through the formation of specific ribonucleoprotein complexes, with fundamental implications in ribosome biogenesis.However, it is becoming increasingly clear that the landscape of sno rna cellular functionality is much broader than it once seemed with novel members, non-uniform expression patterns, new and diverse targets as well as several emerging non-canonical functions ranging from the modulation of alternative splicing to the regulation of chromatin architecture.In order to facilitate the further characterization of human sno rnas in a holistic manner, we introduce an online interactive database tool: sno db.Its purpose is to consolidate information on human sno rnas from different sources such as sequence databases, target information, both canonical and non-canonical from the literature and from high-throughput rna-rna interaction datasets, as well as high-throughput sequencing data that can be visualized interactively.

Journal: Nucleic acids research (2020)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Requirements for an electronic handover system for interprofessional collaboration between psychotherapists and occupational health professionals - a qualitative study.

An electronic handover system provides a potential way to bridge the interface between psychotherapy and occupational health.This qualitative study therefore aimed assessing (1) content-related and (2) functional requirements that psychotherapists and occupational health professionals expect from an electronic handover system to exchange relevant information about their patients with common mental disorders.Methods five focus groups with psychotherapists and occupational health professionals (occupational physicians and members of company integration management) were conducted via video conference using an interview guide.The focus groups were transcribed and content-analysed using maxqda.Results with regard to content-related requirements, information that serve to assess employee's ability to work was described as particularly relevant by occupational physicians and members of company integration management (e.g.Restrictions in certain work areas or ability to work under time pressure).Psychotherapists indicated that information about the employee's working conditions is particularly relevant.This includes description of work tasks or conflicts at the workplace.Concerning functional requirements, all professional groups attached importance to data security and functions to improve communication and collaboration (e.g.The use of standardised handover forms).Conclusion this study provides insight into the desired content-related and functional requirements by psychotherapists, occupational physicians and members of company integration management for an electronic handover system.However, the theoretical and practical development of such a system requires several additional steps, such as the involvement of further relevant stakeholders (e.g.Patients, software developers).

Journal: BMC health services research (2022)
Publication types: Journal Article
Air Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blood.

Venous air embolism, which may complicate medical and surgical procedures, activates complement and triggers thromboinflammation.In lepirudin-anticoagulated human whole blood, we examined the effect of air bubbles on complement and its role in thromboinflammation.Whole blood from 16 donors was incubated with air bubbles without or with inhibitors of c3, c5, c5a r1, or cd14.Complement activation, hemostasis, and cytokine release were measured using elisa and quantitative pcr.Compared with no air, incubating blood with air bubbles increased, on average, c3a 6.5-fold, c3bc 6-fold, c3b bb p 3.7-fold, c5a 4.6-fold, terminal complement complex s c5b9 3.6-fold, prothrombin fragments 1+2 (ptf1+2) 25-fold, tissue factor m rna (tf-m rna) 26-fold, microparticle tissue factor 6.1-fold, β-thromboglobulin 26-fold (allp< 0.05), and 25 cytokines 11-fold (range, 1.5-78-fold; allp< 0.0001).C3 inhibition attenuated complement and reduced ptf1+2 2-fold, tf-m rna 5.4-fold, microparticle tissue factor 2-fold, and the 25 cytokines 2.7-fold (range, 1.4-4.9-fold; allp< 0.05).C5 inhibition reduced ptf1+2 2-fold and tf-m rna 12-fold (allp< 0.05).C5 or cd14 inhibition alone reduced three cytokines, including il-1β (p= 0.02 andp= 0.03).Combined c3 and cd14 inhibition reduced all cytokines 3.9-fold (range, 1.3-9.5-fold;p< 0.003) and was most pronounced for il-1β (3.2- versus 6.4-fold), il-6 (2.5- versus 9.3-fold), il-8 (4.9- versus 8.6-fold), and ifn-γ (5- versus 9.5-fold).Antifoam activated complement and was avoided.Ptf1+2 was generated in whole blood but not in plasma.In summary, air bubbles activated complement and triggered a c3-driven thromboinflammation.C3 inhibition reduced all mediators, whereas c5 inhibition reduced only tf-m rna.Combined c5 and cd14 inhibition reduced il-1β release.These data have implications for future mechanistic studies and possible pharmacological interventions in patients with air embolism.

Journal: Journal of immunology (Baltimore, Md. : 1950) (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Food hygiene and food safety practices of households in a township north of Tshwane, Gauteng.

Foodborne illness is still a major public health concern worldwide.Most cases of foodborne illness can be traced to the home.The food safety practices of food handlers in the household are an important determining factor in food safety at the household level.Aim to assess the food safety practices of food handlers in households in ga-rankuwa, tshwane.Setting the study was conducted in zones 1-9 and zone 16, as well as extension 25 of ga-rankuwa, tshwane.Methods a quantitative descriptive study design was used for which a structured questionnaire was administered among 339 food handlers.Descriptive and inferential statistical analysis was performed in stata 13.1.Results the majority of food handlers reported always washing their hands before (81%) and after handling raw meat, chicken or fish; the majority of food handlers (69%) reported always washing preparation surfaces and utensils with clean, soapy water after handling raw meat, chicken or fish.Less than half (45%) of food handlers reported never thawing frozen meat, chicken or fish in a bowl of cold water.Conclusion the food handlers reported appropriate food safety practices regarding hand washing and food preparation surfaces and utensils.However, their practices regarding the storage of meat, chicken and fish were inappropriate.Contribution this study builds on the existing body of literature on the food safety practices of food handlers.Moreover, the study findings can serve as a basis for the development of interventions to ensure food safety at a household level.

Journal: Health SA = SA Gesondheid (2023)
Publication types: Journal Article
Single-Cell Transcriptomic Atlas of Primate Ovarian Aging.

Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear.We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates (nhps) and identified seven ovarian cell types with distinct gene-expression signatures, including oocyte and six types of ovarian somatic cells.In-depth dissection of gene-expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages.Further analysis of cell-type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age.Additionally, inactivated antioxidative pathways, increased reactive oxygen species, and apoptosis were observed in granulosa cells from aged women.This study provides a comprehensive understanding of the cell-type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.

Journal: Cell (2020)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
The World Health Organization road map for neglected tropical diseases 2021-2030: implications for onchocerciasis elimination programs.

In its new roadmap for neglected tropical diseases, the world health organization proposes three important strategic shifts: (i) stronger accountability which shifting from process to impact indicators; (ii) intensified cross-cutting approaches; and (iii) stronger country ownership.In this paper we discuss the implementation of these three strategies in the setting of a high onchocerciasis disease burden in south sudan.

Journal: Infectious diseases of poverty (2021)
Publication types: Editorial