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X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.

Haptic feedback of gripping forces during robotassisted surgery can benefit the surgical outcome by means of reduced forces applied to the tissue. A custom-designed haptic user interface allows to control four degrees of freedom of the instrument’s endeffector and to display gripping forces. System-centered evaluation is performed to assess its capability of displaying feedback with high mechanical bandwidth. In addition, the perception of gripping forces is evaluated using task-centered methods. Two tasks were performed by ten participants to assess the perceived feedback regarding size and stiffness of grasped objects. Maximum feedback forces of 4.3N and a mechanical bandwidth of 73.5 Hz are achieved. Tests with participants showed promising results regarding the discrimination of size and stiffness of grasped objects.

This paper focuses on determining the cable tension required for a cable-driven endoscopic manipulator to reach a given position under an external load at the end effector. The aim is to restore the initial position of the end effector without an external force. A simulation was performed using MATLAB, where mathematical models and algorithms were used to calculate the required tension. The mathematical model, based on Optimized Motion Estimation Analysis, considers the joint stiffness and the influence of gravity, in addition to the cable tensions and external load. The algorithm minimizes the sum of moments to achieve a stable position. An optical tracking system was used to validate the simulation results against experimental data. The manipulator successfully compensated for an external load of 1.96N and returned to its initial position with adjusted cable tensions. The results showed that the manipulator was deformed by an external load, highlighting the need to adjust the cable tension for position compensation. The discrepancies between the experimental and simulation results were due to factors such as marker size, as well as joint imperfections due to manufacturing and friction effects. Nevertheless, the proposed method proved to be effective in compensating for external loads and restoring the manipulator to the desired position.

Concentric tube robots (CTR) have gained popularity in robotic research due to their potential for smaller instrument sizes, enhanced dexterity and reduced trauma. However, CTR control can be complex, with tip direction and curvature being kinematically coupled. To address this, a symmetric eccentric tube robot (ETR) is presented, where three identical pre-curved wires are arranged in parallel and constrained by an outer sheath. Instrument curvature is controlled by a single input angle. This study aims to demonstrate the suitability as manually actuated instrument. A model for curvature as a function of input angle is presented, and a prototype ETR with an outer diameter of 1 mm is assembled and evaluated. The results show that the ETR follows the expected shape, the curvature decreasing with the separation angle in an almost linear way that may be perceived as intuitive and predictable by the human user. However, some unsteady behavior (snapping) is observed, which may be addressed by preventing torsion of the wires through mechanical means. The simplified model neglecting the sheath stiffness provides precise enough predictions for the working space of a manual ETR. The findings suggest that manual ETRs have potential applications in superficial interventions, such as injections, arthroscopy, or ophthalmic surgery, where their curved section can be beneficial in comparison to current straight needles. Further research could explore interlocking mechanical designs to prevent torsion or modular setups for enhanced functionality.

Abstract We developed and validated the Influenza Severity Scale (ISS), a standardized risk assessment for influenza, to estimate and predict the probability of major clinical events in patients with laboratory-confirmed infection. Data from the Canadian Immunization Research Network’s Serious Outcomes Surveillance Network (2011/2012–2018/2019 influenza seasons) enabled the selecting of all laboratory-confirmed influenza patients. A machine learning-based approach then identified variables, generated weighted scores, and evaluated model performance. This study included 12,954 patients with laboratory-confirmed influenza infections. The optimal scale encompassed ten variables: demographic (age and sex), health history (smoking status, chronic pulmonary disease, diabetes mellitus, and influenza vaccination status), clinical presentation (cough, sputum production, and shortness of breath), and function (need for regular support for activities of daily living). As a continuous variable, the scale had an AU-ROC of 0.73 (95% CI, 0.71–0.74). Aggregated scores classified participants into three risk categories: low (ISS

Introduction Persons after stroke experience limitations in activities of daily living even in the chronic phase. Many patients who had a stroke report mobility limitations with loss of social roles such as reduced gait-related participation. International best-practice recommendations for patients who had a stroke include interprofessional diagnostics as a core element for goal setting and intervention planning to improve social participation. Interprofessional diagnostics has not yet been implemented in Germany.Methods and analysis The aim is to develop an interprofessional diagnostic toolkit. This will be done in a multi-step process: first, an integrative review is conducted to synthesise the literature. Second, the experiences regarding diagnostics and walking outside is captured in focus groups with persons after stroke, relatives and health professionals. Third, a toolkit for the interprofessional diagnostic process of gait-related-participation will be developed based on the results of the previous steps in a future workshop. Fourth, the results of each work package will be integrated into the iterative development process for evaluation and implementation. All steps will be performed in accordance with the respective reporting guidelines.Ethics and dissemination This study has been approved by the ethics committee at the Ludwig Maximilians University (LMU), Germany and is overseen by LMU-Medical Institutional Review Board. Written informed consent will be obtained from all participants. Results will be disseminated through knowledge exchange with stakeholders and in peer-reviewed journal publications, scientific conferences, formal and informal reports. Stakeholders, patients and providers will be involved in most steps of the development from the beginning, which will facilitate later implementation at a larger scale.Trial registration number German Register Clinical Trials/Deutsches Register Klinischer Studien DRKS00032389.

ABSTRACT The Serra da Bodoquena National Park is an important protected area that promotes the conservation of a threatened ecosystem, the Dry Forest. It comprises two major fragments of predominantly Seasonally Dry Forest vegetation. The two fragments are under different protection schemes because they are considered different biomes. The southern fragment is considered part of the Atlantic Forest biome, and is thus protected by the Atlantic Forest Law, while the northern one is considered part of the Cerrado biome and is protected by the Native Vegetation Protection Law of Brazil (2012). This difference affects management and threatens the conservation of the National Park. The Native Vegetation Protection Law is more permissive, thus increasing the conflicts between the park and surroundings in the northern fragment. We used floristic composition to provide a more accurate definition for the two fragments with regard to their phytogeographical domain. Our results identified high floristic similarity between the fragments, indicating the same vegetation type for both. Among the 202 plant species identified in this study, 76% belong to the Atlantic Forest biome. This relatively high proportion indicates that the predominant vegetation and species composition of the National Park is typical of the Atlantic Forest. The occurrence of fragments of the Atlantic Forest, with a representative number of species of its flora outside the area of application of the law of the Atlantic Forest, defined by Decree No. 6.660 / 2008, indicates the need to elaborate or adapt the law to protect these fragments.

Objective: This study aimed to compare the precision of a temporomandibular joint (TMJ)-related bite-registration technique with the occlusion-related registration technique using various polyvinyl siloxane materials. Methods: The interocclusal relation of 40 patients was transferred to stone casts by bite registrations using polyvinyl siloxane materials with different Shore harnesses (SH) values including Registrado clear (SH=70 A), Registrado xtra (SH=51 D) and Registrado scan (SH=90A). A joint-related registration technique (called the Gerber technique or gothic arch tracing) was also applied in all patents. The clinical contact situation and the contacts on stone casts were marked and transferred to a 3D-measuring software. The deviation of the occlusal contacts on the stone casts to the clinical reference was measured and compared between the registration methods. Results: There was no statistically significant difference in contact deviation values between different types of registration methods (P=0.093). However, the frequency of missing contacts was significantly greater in the Gerber technique compared to the occlusion-related bite registrations (P0.05).Conclusions: The hardness of the polyvinyl siloxane materials for occlusion-related bite registration did not affect the precision of the registration techniques in dentulous patients. Polyvinyl siloxane materials should be preferred for joint-related registration in TMD patients

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player of lipid metabolism with higher plasma levels in women throughout their life. Statin treatment affects PCSK9 levels also showing evidence of sex-differential effects. It remains unclear whether these differences can be explained by genetics. Methods We performed genome-wide association meta-analyses (GWAS) of PCSK9 levels stratified for sex and statin treatment in six independent studies of Europeans (8936 women/11,080 men respectively 14,825 statin-free/5191 statin-treated individuals). Loci associated in one of the strata were tested for statin- and sex-interactions considering all independent signals per locus. Independent variants at the PCSK9 gene locus were then used in a stratified Mendelian Randomization analysis (cis-MR) of PCSK9 effects on low-density lipoprotein cholesterol (LDL-C) levels to detect differences of causal effects between the subgroups. Results We identified 11 loci associated with PCSK9 in at least one stratified subgroup (p

Introduction. The COVID-19 pandemic, etiologically related to SARS-CoV-2, was the longest-lasting pandemic for an acute respiratory disease and had a significant impact on demography, economics and politics globally. Experiences with this pandemic are significant for the sustainable development of human society. A detailed analysis of these experiences in epidemic control should include details of the pathogen evolution down to the regional level. The aim of the study was to establish the regularities of the COVID-19 epidemic process in connection with the change of the pathogen genetic variants on the territory of Primorsky Krai. Materials and methods. A retrospective epidemiological analysis of COVID-19 incidence and dynamics of circulation of SARS-CoV-2 genetic variants during the pandemic of this disease (11.03.2020–05.05.2023) in Primorsky Krai was carried out. Data was gathered from the Department of Rospotrebnadzor in Primorsky Krai, the Centre of Hygiene and Epidemiology in Primorsky Krai, as well as the G.P. Somov Research Institute of Epidemiology and Microbiology of the Russian Federation and Russian Platform for Aggregation of Information on Virus Genomes (VGARus). In particular, 1055 nucleotide sequences of full-length SARS-CoV-2 genomes from Primorsky Krai, among which 553 were sequenced at the G.P. Somov Research Institute of Epidemiology and Microbiology were included in analysis. Results. When analyzing the epidemic dynamics of COVID-19 in Primorsky Krai (2020–2023), 7 rises in incidence with different clinical and epidemiological symptoms depending on the genetic variants of the pathogen were identified. At the beginning of the pandemic in Primorsky Krai, as well as throughout Russia, Wuhan-like variants of SARS-CoV-2 were predominant, though later, Delta and Omicron genetic variants were in the majority. By the end of April — beginning of May 2023, the proportion of Omicron sub-variants (XBB.1.9.2 and XBB.1.16) in Primorsky Krai was higher than the Russian average and comparable to that in neighboring countries (Republic of Korea and Japan). Conclusion. Due to the ongoing evolution of SARS-CoV-2, the possibility of the emergence of new pathogens, the peculiarities of the geographical location as well as political and economic importance of Primorsky Krai, it is necessary to consistently improve regional capabilities for operational molecular virological monitoring.

Phlebia radiata is a widespread white-rot basidiomycete fungus with significance in diverse biotechnological applications due to its ability to degrade aromatic compounds, xenobiotics, and lignin using an assortment of oxidative enzymes including laccase. In this work, a chemical screen with 480 conditions was conducted to identify chemical inducers of laccase expression in P. radiata. Among the chemicals tested, phenothiazines were observed to induce laccase activity in P. radiata, with promethazine being the strongest laccase inducer of the phenothiazine-derived compounds examined. Secretomes produced by promethazine-treated P. radiata exhibited increased laccase protein abundance, increased enzymatic activity, and an enhanced ability to degrade phenolic model lignin compounds. Transcriptomics analyses revealed that promethazine rapidly induced the expression of genes encoding lignin-degrading enzymes, including laccase and various oxidoreductases, showing that the increased laccase activity was due to increased laccase gene expression. Finally, the generality of promethazine as an inducer of laccases in fungi was demonstrated by showing that promethazine treatment also increased laccase activity in other relevant fungal species with known lignin conversion capabilities including Trametes versicolor and Pleurotus ostreatus.

BackgroundThe COVID-19 pandemic caused graduate medical education (GME) programs to pivot to virtual interviews (VIs) for recruitment and selection. This systematic review synthesizes the rapidly expanding evidence base on VIs, providing insights into preferred formats, strengths, and weaknesses.MethodsPubMed/MEDLINE, Scopus, ERIC, PsycINFO, MedEdPublish, and Google Scholar were searched from 1 January 2012 to 21 February 2022. Two authors independently screened titles, abstracts, full texts, performed data extraction, and assessed risk of bias using the Medical Education Research Quality Instrument. Findings were reported according to Best Evidence in Medical Education guidance.ResultsOne hundred ten studies were included. The majority (97%) were from North America. Fourteen were conducted before COVID-19 and 96 during the pandemic. Studies involved both medical students applying to residencies (61%) and residents applying to fellowships (39%). Surgical specialties were more represented than other specialties. Applicants preferred VI days that lasted 4-6 h, with three to five individual interviews (15-20 min each), with virtual tours and opportunities to connect with current faculty and trainees. Satisfaction with VIs was high, though both applicants and programs found VIs inferior to in-person interviews for assessing 'fit.' Confidence in ranking applicants and programs was decreased. Stakeholders universally noted significant cost and time savings with VIs, as well as equity gains and reduced carbon footprint due to eliminating travel.ConclusionsThe use of VIs for GME recruitment and selection has accelerated rapidly. The findings of this review offer early insights that can guide future practice, policy, and research.

ABSTRACT Landoltia punctata is a species of duckweed originating from India, but has been recorded in all continents, except Antarctica. It is of economic interest, being used in phytoremediation, but mainly due to its high invasive potential. Here we report the first record of this species in the Amazon region, both expanding its known distribution and raising awareness about the potential losses of biodiversity that may occur in the kind of environment where the species was registered. Future studies should focus on the competitive potential and population control of L. punctata in the region.

Summary: A key issue for research on COVID-19 pathogenesis is the lack of biopsies from patients and of samples at the onset of infection. To overcome these hurdles, hamsters were shown to be useful models for studying this disease. Here, we further leverage the model to molecularly survey the disease progression from time-resolved single-cell RNA sequencing data collected from healthy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected Syrian and Roborovski hamster lungs. We compare our data to human COVID-19 studies, including bronchoalveolar lavage, nasal swab, and postmortem lung tissue, and identify a shared axis of inflammation dominated by macrophages, neutrophils, and endothelial cells, which we show to be transient in Syrian and terminal in Roborovski hamsters. Our data suggest that, following SARS-CoV-2 infection, commitment to a type 1- or type 3-biased immunity determines moderate versus severe COVID-19 outcomes, respectively.

Abstract Root growth is crucial in crop production and is influenced by soil attributes, but also affects soil chemical, physical and biological quality, along with management and conservation practices. In this paper, soybean root growth data from a field study at Guarapuava, Paraná State, Brazil are examined. In 2019, at a farm with over 35 years of no-tillage system (NT) adoption, three management sets were established in 1,1 ha macroplots: 1) farmer's NT standard (FNT), without terraces, with downhill farming and with autumn fallow; 2) autumn cover crops and contour farming added to FNT, as best management practices (BMP); 3) terraces and contour farming (TC) added to FNT. Soybean was sowed in November 2020 and 2021, and minirhizotron tubes (1 m long, 7 cm wide) were installed into the soil just after soybean emerged in 2020. Root length, area, volume, and diameter were evaluated with the help of a root scanner. Data were submitted to descriptive statistics. The added conservation practices improved root length, area and volume, significantly for BMP in the subsoil (40-60 cm) compared to FNT standard. Minirhizotron enabled the study of roots in the field, but data variability was high, so that for annual crops with pivoting roots like soybean, root observation points (6 per plot) must be increased, and crop stand close to the observation points is a critical font of error.

Abstract Background Influenza and RSV coinfections are not commonly seen but are concerning as they can lead to serious illness and adverse clinical outcomes among vulnerable populations. Here we describe the clinical features and outcomes of influenza and RSV coinfections in hospitalized adults. Methods A cohort study was performed with pooled active surveillance in hospitalized adults ≥ 50 years from the Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) during the 2012/13, 2013/14, and 2014/15 influenza seasons. Descriptive statistics summarized the characteristics of influenza/RSV coinfections. Kaplan-Meier estimated the probability of survival over the first 30 days of hospitalization. Results Over three influenza seasons, we identified 33 cases of RSV and influenza coinfection, accounting for 2.39 cases per 1,000 hospitalizations of patients with acute respiratory illnesses. Adults aged 50 + years commonly reported cough (81.8%), shortness of breath (66.7%), sputum production (45.5%), weakness (33.3%), fever (27.3%), and nasal congestion (24.2%) as constitutional and lower respiratory tract infection symptoms. The mortality rate was substantial (12.1%), and age, comorbidity burden, and frailty were associated with a higher risk for adverse clinical outcomes. Conclusions Older adults are at higher risk for complications from influenza and RSV coinfections, especially those over 65 with a high comorbidity burden and frailty.

Abstract X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.