bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion ofMEC1suppresses replicative senescence of thecdc13-2mutant inSaccharomyces cerevisiae
Authors: Yao Yue , Fekete-Szücs Enikő , Rosas Bringas Fernando R. , Chang Michael 
Published: February 2023

AbstractInSaccharomyces cerevisiae, telomerase recruitment to telomeres depends on a direct interaction between Cdc13, a protein that binds single-stranded telomeric DNA, and the Est1 subunit of telomerase. Thecdc13-2allele disrupts telomerase association with telomeres, resulting in progressive telomere shortening and replicative senescence. The Mec1/ATR kinase is both a positive and negative regulator of telomerase activity, and is required for the cell cycle arrest in telomerase-deficient senescent cells. In this study, we find that deletion ofMEC1suppresses the replicative senescence ofcdc13-2. This suppression is dependent on telomerase, indicating that Mec1 antagonizes telomerase-mediated telomere extension incdc13-2cells to promote senescence.
Dissemination of IncI plasmid encodingblaCTX-M-1is not hampered by its fitness cost in the pig’s gut
Authors: Allain Margaux , Mahérault Anne Claire , Gachet Benoit , Martinez Caroline , Condamine Bénédicte , Magnan Mélanie , Kempf Isabelle , Denamur Erick , Landraud Luce 
Published: February 2023

ABSTRACTMultiresistance plasmids belonging to the IncI incompatibility group have become one of the most pervasive plasmid types in extended-spectrum beta-lactamase producingEscherichia coliof animal origin. The extent of the burden imposed on the bacterial cell by these plasmids seems to contribute to the emergence of “epidemic” plasmids. However,in vivodata in the natural environment of the strain are scarce. Here, we investigated the cost of ablaCTX-M-1-IncI1 epidemic plasmid in a commensalE. colianimal strain, UB12-RC, before and after oral inoculation of fifteen 6-to 8-week-old specific pathogen-free pigs. Growth rate in rich medium was determined on (i) UB12-RC and derivatives, with or without plasmid,in vivoand/orin vitroevolved, and (ii) strains that acquired the plasmid in the gut during the experiment. AlthoughblaCTX-M-1-IncI1 plasmid imposed no measurable burden on the recipient strain after conjugation and during the longitudinal carriage in the pig’s gut, we observed a significant difference in the bacterial growth rate between IncI1 plasmid-carrying and plasmid-free isolates collected duringin vivocarriage. Only a few mutations on the chromosome of the UB12-RC derivatives were detected by whole-genome sequencing. RNA-Seq analysis of a selected set of these strains showed that transcriptional responses to theblaCTX-M-1-IncI1 acquisition were limited, affecting metabolism, stress response, and motility functions. Our data suggest that the effect of IncI plasmid on host cells is limited, fitness cost being insufficient to act as a barrier to IncI plasmid spread among natural population ofE. coliin the gut niche.
The Hidden Footprints of Platelets in IgG4-Related Disease Pathogenesis
Authors: Oguz Ali Kemal , Oygur Cagdas Sahap , Dedeoglu Bala Gur , Turacli Irem Dogan , Kilicoglu Sibel Serin , Ergun Ihsan 
Published: February 2023

AbstractPlatelets have grabbed great attention as immune cells and principal modulators of tissue remodeling besides their well-known hemostatic and vascular wall safeguarding functions. In line with this knowledge, findings indicating an excessive platelet activation have been reported in systemic sclerosis, which is an autoimmune, multisystem, fibrotic disorder. By borrowing the transcriptomic data of Nakajima et al. (GEO data repository, GSE66465) we sought a platelet contribution in immunoglobulin G4-related disease (IgG4-RD) pathogenesis, another immune-mediated, fibroinflammatory, multiorgan disease. GEO2R for class comparisons and WebGestalt for functional enrichment analyses were used. When treatment naïve IgG4-RD patients were compared with healthy controls, 268 differentially expressed genes (204 with increased and 64 with decreased expression) were detected. Enrichment analyses performed using gene ontology (Biological Process), pathway (Panther), and disease (GLAD4U) functional databases documented many significantly enriched terms relating to platelets, coagulation, and thrombosis, including “ Thrombasthenia”, “ Low on-treatment platelet reactivity”, “ High on-treatment platelet reactivity”, “ Platelet reactivity”, “ Platelet aggregation inhibition”, “ Blood platelet disorders”, “ Platelet degranulation”, “ Platelet aggregation”, and “ Platelet activation”. The enrichment ratios of these terms were found to be between 6.4 and 83.2. Together with the limited data in the relevant literature, it seems imperative to plan meticulously designed research specifically focusing on platelets’ contribution to IgG4-RD pathogenesis.
Mortality Predictions for Men and Women Diagnosed with Anal Canal Squamous Cell Carcinoma in the United States
Authors: Ahmmad Roungu , Hosseini-Carroll Pegah , Hossain Sanwar , Muthukumaru Raina 
Published: February 2023

ABSTRACTObjectiveStudies have concluded that treatments for patients with anal cancer vary based on their age, sex, and race. We examined gender-specific differences in mortality and overall survival for patients with squamous cell carcinoma (SCC) of the anal canal (AC), based on differences in treatment, stage and demographic factors.MethodSEER’s retrospective cohort dataset was used to review all patients diagnosed with SCC of the AC between 2000 and 2018. We analyzed survival by sub-distributed Cox models and estimated overall survival probabilities through nomograms based on cancer treatments, tumor characteristics, and demographic dataResultsIn the study, 24,892 patients with SCC in the AC had a median survival time of 43 months (IQR: 16-97). However, males (median 38.0 months, IQR: 13.0-92.0) had significantly shorter median survival times than females (median 46.0 months, IQR: 17-100). There were 12% of patients in metastatic stages, with females (70.3%) receiving more treatments than males (29.7%). The survival rate of patients with SCC of the AC who underwent radiation treatment was significantly higher (HR 0.72, 95% CI: 0.65-0.80, p<0.001). Moreover, compared to those without surgery on the primary site, those undergoing surgery on the primary site had a 49% lower mortality rate (HR 0.51; 95% CI: 0.45 to 0.56, p0.001). According to the study, the overall survival probability at 5 and 10 years for patients who received chemotherapy on primary sites was about 90%, compared to only 40% and 22% for those who did not receive chemotherapy. Surgical intervention yielded similar results, but radiation therapy did not significantly improve survival rates.ConclusionCompared with men, women with SCC of the AC have a higher survival rate, and younger patients tend to live longer. The factors negatively affecting survival were increasing age, non-whites, divorced / separated / widowed, and advanced stages of cancer. A significant increase in survival was seen after surgery and chemotherapy for SCC, while radiation had little effect on survival.
How Much of the Outcome Improvement after Successful Recanalization is Explained by Follow-up Infarct Volume Reduction?
Authors: Kniep Helge , Meyer Lukas , Broocks Gabriel , Bechstein Matthias , Austein Friederike , McDonough Rosalie , Brekenfeld Caspar , Flottmann Fabian , Deb-Chatterji Milani , Alegiani Anna , Hanning Uta , Thomalla Götz , Fiehler Jens , Gellißen Susanne ,   the German Stroke Registry – Endovascular Treatment (GSR – ET)
Published: February 2023

ABSTRACTBackgroundFollow-up infarct volume (FIV) is used as surrogate for treatment efficiency in Mechanical Thrombectomy (MT). In contrast to these assumptions, previous works suggest that MT-related infarct volume reduction has only limited association with outcome comparing MT vs. medical care. It remains unclear to what extent the causal relationship between successful recanalization vs. persistent occlusion and functional outcome is explained by treatment-related reduction in FIV. Results might allow quantification of pathophysiological effects and could improve the understanding of the value of FIV as imaging endpoint in clinical trials.MethodsAll patients from our institution enrolled in the German Stroke Registry from 05/2015-12/2019 with anterior circulation stroke, availability of the relevant clinical data and follow-up CT were analyzed. A mediation analysis was conducted to investigate the effect of successful recanalization (Tici≥2b) on good functional outcome (90d mRS≤2) with mediation through final infarct volume.Results429 patients were included. 309(72 %) patients had a successful recanalization and 127(39%) achieved good functional outcome. Probability of good outcome was significantly associated with age (OR=0.89,p<0.001), pre-stroke mRS (OR=0.38,p<0.001), FIV (OR=0.98,p<0.001), hypertension (OR=2.08,p<0.05) and successful recanalization (OR=3.57,p<0.01). Using linear regression in the mediator pathway, FIV was significantly associated with ASPECTS (Coefficient(Co)=-26.13,p<0.001), NIHSS admission (Co=3.69,p<0.001), age (Co=-1.18,p<0.05) and successful recanalization (Co=-85.22,p<0.001). Mediation analysis suggest a 23 percentage points (pp) increase of probability of good functional outcome (95%CI:16pp-29pp) in patients with successful recanalization. 56% (95%CI:38%-78%) of the improvement in good outcome was explained FIV reduction.Conclusions56% of the improvement of functional outcome after successful recanalization is explained by FIV reduction. Results corroborate established pathophysiological assumptions and confirm the value of infarct volume as imaging endpoint in clinical trials. 44% of the improvement in outcome is not explained by FIV reduction and reflects the remaining mismatch between radiological and clinical outcome measures.Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT03356392(NCT03356392)
Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features
Authors: Martelloni Gabriele , Turchi Alessio , Fallerini Chiara , Degl’Innocenti Andrea , Baldassarri Margherita ,   GEN-COVID Multicenter study, Olmi Simona , Furini Simone , Renieri Alessandra 
Published: February 2023

ABSTRACTThe impact of common and rare variants in COVID-19 host genetics is widely studied in [16]. Here, common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. Firstly, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score, the so called IPGS, which offers a very simple description of the contribution of host genetics in COVID-19 severity. IPGS leads to an accuracy of 55-60% on different cohorts and, after a logistic regression with in input both IPGS and the age, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using the information on the host organs involved in the disease. We generalized the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features”, inspired by the Quantum Mechanics. The organs’ coefficients were set via the application of the genetic algorithm Pygad and, after that, we defined two new Integrated PolyGenic Score (and). By applying a logistic regression with both(or indifferently) and age as input, we reach an accuracy of 84-86%, thus improving the results previously shown in [16] by a factor of 10%.
Nuclear genetic background influences the phenotype of theDrosophila tko25tmitochondrial protein-synthesis mutant
Authors: Jacobs Howard T. , Tuomela Tea , Lillsunde Päivi 
Published: February 2023

ABSTRACTTheDrosophila tko25tpoint mutation in the gene encoding mitoribosomal protein S12 produces a complex phenotype of multiple respiratory chain deficiency, developmental delay, bang-sensitivity, impaired hearing, sugar and antibiotic sensitivity and impaired male courtship. Its phenotypic severity was previously shown to be alleviated by inbreeding, and to vary with mitochondrial genetic background. Here we show similarly profound effects conferred by nuclear genetic background. We backcrossedtko25tinto each of two standard nuclear backgrounds, Oregon R andw1118, the latter used as recipient line in many transgenic applications requiring selection for thewhiteminigene marker. In thew1118background,tko25tflies showed a moderate developmental delay and modest bang-sensitivity. In the Oregon R background, males showed longer developmental delay and more severe bang-sensitivity, and we were initially unable to produce homozygoustko25tfemales in sufficient numbers to conduct a meaningful analysis. When maintained as a balanced stock over 2 years,tko25tflies in the Oregon R background showed clear phenotypic improvement though were still more severely affected than in thew1118background. Phenotypic severity did not correlate with the expression level of thetkogene. Analysis of tko25t hybrids between the two backgrounds indicated that phenotypic severity was conferred by autosomal, X-chromosomal and parent-of-origin dependent determinants. Although some of these effects may betko25t-specific, we recommend that, in order to minimize genetic drift and confounding background effects, the genetic background of non-lethal mutants should be controlled by regular backcrossing, even if stocks are usually maintained over a balancer chromosome.
Using pose estimation and 3D rendered models to study leg-mediated self-righting by lanternflies
Authors: Bien Theodore , Alexander Benjamin H. , Li Chengpei , Goeler-Slough Natalie , Tonia Hsieh S. , Kane Suzanne Amador 
Published: February 2023

AbstractThe ability to upright quickly and efficiently when overturned on the ground (terrestrial self-righting) is crucial for living organisms and robots. Previous studies have mapped the diverse behaviors used by various animals to self-right on different substrates, and proposed physical models to explain how body morphology can favor specific self-righting methods. However, to our knowledge no studies have quantified and modeled all of an animal’s limb motions during these complicated behaviors. Here, we studied terrestrial self-righting for nymphs of the invasive spotted lanternfly (Lycorma delicatula), an insect that must frequently recover from being overturned after jumping and falling in its native habitat. These nymphs self-righted successfully in 92-100% of trials on three substrates with different friction and roughness, with no significant difference in the time or number of attempts required. They accomplished this using three stereotypic sequences of movements. To understand these motions, we combined 3D poses tracked on multi-view high-speed video with articulated 3D models created using photogrammetry and Blender rendering software. The results were used to calculate the mechanical properties (e.g., potential and kinetic energy, angular speed, stability margin, torque, force, etc.) of these insects during righting trials. We used an inverted physical pendulum model (a “template”) to estimate the kinetic energy available in comparison to the increase in potential energy required to flip over. While these insects began righting using primarily quasistatic motions, they also used dynamic leg motions to achieve final tip-over. However, this template did not describe important features of the insect’s center of mass trajectory and rotational dynamics, necessitating the use of an “anchor” model comprising the 3D rendered body model and six articulated two-segment legs to model the body’s internal degrees of freedom and capture the role of the legs’ contribution to inertial reorientation. This anchor elucidated the sequence of highly coordinated leg movements these insects used for propulsion, adhesion, and inertial reorientation during righting, and how they frequently pivot about a body contact point on the ground to flip upright. In the most frequently used method, diagonal rotation, these motions allowed nymphs to spin their bodies to upright with lower force with a greater stability margin compared to the other less frequently-used methods. We provide a concise overview of necessary background on 3D orientation and rotational dynamics, and the resources required to apply these low-cost modeling methods to other problems in biomechanics.
Development of minimum reporting sets of patient characteristics in epidemiological research: a methodological systematic review
Authors: Vuong My Luong , Trang Tu Pham Hien , Duong Khanh Linh , Vo Tat-Thang 
Published: February 2023

AbstractBackgroundCore patient characteristic sets (CPCS) are increasingly developed to identify variables that should be reported to describe the target population of epidemiological studies in the same medical area, while keeping the additional burden on the data collection acceptable.MethodsWe conduct a systematic review of primary studies/ protocols published aiming to develop CPCS, using the PubMed database. We particularly focus on the study design and the characteristics of the proposed CPCS. Quality of Delphi studies was assessed by a tool prosposed in the literatue. All results are reported descriptively.ResultsAmong 23 eligible studies, Delphi survey is the most frequently used technique to obtain consensus in CPCS development (69.6%, n=16). Most studies do not include patients as stakeholders. The final CPCS rarely include socioeconomic factors. 60.9% (n=14) and 31.6% (n=6) of studies provide definition and recommend measurement methods for items, respectively.ConclusionThis study identified a considerable variation and suboptimality in many methodological aspects of CPCS studies. To enhance the credibility and adoption of CPCS, a standard for conducting and reporting CPCS studies is warranted.FundingNo funds, grants, or other support were received during the preparation of this manuscript.RegistrationThis review was not pre-registered.
Non-Communicable Disease Service Readiness in Nepal: A Further Analysis of Nepal Health Facility Survey- 2021
Authors: Adhikari Bikram , Pandey Achyut Raj , Lamichhane Bipul , Saugat Pratap KC , Joshi Deepak , Regmi Shophika , Giri Santosh , Baral Sushil Chandra 
Published: February 2023

AbstractObjectiveTo assess the readiness of public and private health facilities(HFs) in delivering Cardiovascular Diseases(CVDs), Diabetes Mellitus(DM), Chronic Respiratory Diseases(CRDs), and Mental Health(MH) services in Nepal.MethodsWe analyzed data on service readiness for CVDs, DM, CRDs, and MH from Nepal Health Facility Survey 2021 using Service Availability and Readiness Assessment manual of the World Health Organization. Readiness score was measured as the average availability of tracer items in percent, and facilities were considered “ready” for Non-Communicable Diseases (NCDs) management if scored ≥70 (out of 100). We performed weighted descriptive analysis, univariate and multivariable logistic regression to determine association of readiness of HFs with province, type of HFs, ecological region, quality assurance activities, external supervision, client’s opinion review, and frequency of HF meetings. The result of regression analysis are presented as odds ratio with 95% confidence interval(CI) and p-value.ResultsOf 1581 facilities offering any NCDs related services, 93.1%(95% CI: 90.9 to 94.7), 75.8%(95%CI: 72.4 to 78.8), 99.3%(95%CI: 98.3 to 99.7) and 26.0%(95%CI: 23.0 to 29.2) provide CVDs, DM, CRDs and MH-related services respectively. The overall readiness score for CVDs, DM, CRDs, and MH-related services were 38.1±15.4, 38.5±16.7, 32.6±14.7 and 24.0±23.1 respectively with readiness score lowest for the guidelines and staff training domain and highest for essential equipment and supplies domain. Peripheral public HFs were more likely to be ready to provide all NCDs-related services as compared to federal/provincial facilities. The HFs with external supervision in past 4 months were less likely to be ready to provide CRDs and DM related services and HFs reviewing client’s opinions were more likely to be ready to provide CRDs, CVDs and DM related services.ConclusionReadiness of HFs to provide CVDs, DM, CRDs, and MH-related services was sub-optimal in Nepal. It is recommended to reform policy to improve service readiness for NCDs.Strengths and limitations of this studyNationally representative sample of health facilities in Nepal, with coverage of all seven provinces and 77 districtsSurvey has adopted a highly standardized survey with the globally accepted research protocol. Variables for readiness analysis are based on standardized WHO’s SARA guideline and thus, findings are comparable to findings from other countries.Weighted analysis has been performed, which takes into account the complex sampling procedures and adjusts for non-response and disproportionate sampling.Since the survey was conducted while the COVID-19 pandemic was ongoing, there could be some impact of the pandemic on study results.
Who Wears the Face Mask? Preventive Measures Against COVID-19 in Latin America Before Vaccination
Authors: Rentería Elisenda , Gómez-Casillas Amalia , Zueras Pilar 
Published: February 2023

AbstractThe COVID-19 pandemic outbreak imposed the use of the sanitary mask as a protective measure to reduce the spread of the pandemic, recommended by the World Health Organization. However, the use of the face mask has been uneven and determined by individual, regional, cultural, and political factors. Based on data from the Latinobarometer, we aim to understand the profile of people who used a mask in the context of the COVID-19 pandemic in 18 countries of Latin America, between October and November 2020, right before the mass vaccination campaigns. Results show that women, older people, those with higher education, being employed and not working in temporarily jobs, retirees, students, people with a centrist political ideology, and Catholics, had a higher chance of using a face mask on a regular basis. People living in Venezuela, Chile, Costa Rica and Brazil were the most likely to use face masks. These results call attention to the need to understand social forces behind the willingness to adopt non-pharmacological preventive measures in order to make them more effective in health crisis emergencies.