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The development of motion sensors for monitoring cattle behaviour has enabled farmers to predict the state of their cattle's welfare more efficiently. While most studies work with one dimensional output with disjunct behaviour categories, more accurate prediction can still be achieved by including complex movements and enriching the sensor algorithm to detect multi-dimensional movements, i.e., more than one movement occurring simultaneously. This paper presents such a machine-learning method for analysing overlapping independent movements. The output of the method consists of automatically recognized complex behaviour patterns that can be used for measuring animal welfare, predicting calving, or detecting early signs of diseases. This study combines automated motion sensors (i.e., halter and pedometer) for ruminants known as RumiWatch mounted on a Charolais fattening bull and camera observation. Fourteen types of complex movements were identified, i.e., defecating-urinating, eating, drinking, getting up, head movement, licking, lying down, lying, playing-aggression, rubbing, ruminating, sleeping, standing, and stepping. As multiple parallel binary classificators were used, the system was able to recognize parallel behavioural patterns with high fidelity. Two types of machine learning, i.e., Support Vector Classification (SVC) and RandomForest were used to recognize different general and non-general forms of movement. Results from these two supervised learning systems were compared. A continuous forty-eight hours of video were annotated to train the systems and validate their predictions. The success rate of both classifiers in recognizing special movements from both sensors or separately in different settings (i.e., window and padding) was examined. Although the two classifiers produced different results, the ideal settings showed that all forms of movement in the subject animal were successfully recognized with high accuracy. More studies using more individual animals and different ruminants would increase our knowledge on enhancing the system's performance and accuracy.

Audience: Emergency medicine (EM) residents. This simulation curriculum may also be utilized for senior medical students conducting EM rotations.Background: Ophthalmologic education represents only a small portion of medical school curriculums and continues to decrease over time, leaving physicians poorly equipped to diagnose and manage eye complaints.1 Of emergency physicians (EPs) surveyed, 72.5% felt that they could diagnose orbital compartment syndrome (OCS), yet only 40.3% felt comfortable performing a necessary lateral canthotomy and cantholysis (LCC).2 These survey results demonstrate the urgent need for improved ophthalmology education in EM residency to help us diagnose and manage potentially vision-threatening pathology.Educational Objectives: By the end of this simulation, learners will be able to: 1) demonstrate the major components and a systematic approach to the emergency ophthalmologic examination, 2) develop a differential diagnosis of sight-threatening etiologies that could cause eye pain or vision loss, 3) demonstrate proficiency in performing potentially vision-saving procedures within the scope of EM practice.Educational Methods: Low-fidelity simulation was conducted using a novel model adapted from that used by Phillips et al. during their ophthalmology day in the Department of Emergency Medicine at Vanderbilt University.3 The simulation case was developed by an interdepartmental team of ophthalmologists and EPs at our institution.Research Objectives: To evaluate for statistically significant changes in self-efficacy, knowledge, and performance after an educational intervention. Our primary outcome was defined as a checklist-based performance on a simulated case of orbital compartment syndrome necessitating LCC.Research Methods: We conducted a single-center prospective pre- and post-interventional study evaluating the impact of an educational intervention on EM resident management of a simulated case of OCS. Our two- part study intervention consisted of a lecture on OCS followed by a four and a half hour ophthalmology education day (OED). Residents were evaluated using self-efficacy scales (SES), multiple-choice questions (MCQ), and a performance checklist (developed via a modified Delphi process) at three timepoints: Pre- intervention, immediate post-intervention, and three months post-intervention. Post-graduate year (PGY)-1 through PGY-4 EM residents at an Urban Level 1 Trauma Center participated.Results: Initial recruitment consisted of 18 residents (PGY-1 through PGY-4), and 16 residents (PGY-1 through PGY-3) completed the study. Nine residents participated in the OED and seven residents did not. There were no pre-existing differences in median checklist-based performance, MCQ, or SES scores prior to the intervention. At three months post-OED, the OED attendees scored statistically significantly higher on checklist-based performance than non-attendees (lecture only).Discussion: Ophthalmology education in physician training is limited, and EP comfort with performing vision- saving procedures is poor. We developed a simulation case involving such a vision-saving procedure as well as an ophthalmology curriculum that increased skill retention surrounding management of ophthalmologic emergencies.Topics: Emergency medicine (EM), ophthalmology, orbital compartment syndrome (OCS), retrobulbar hematoma, vision loss, eye pain.

ABSTRACT: The objectives of this study were to determine the farm-level hyperketolactia (HKL) prevalence, as diagnosed from the milk BHB concentration, on dairy farms milking with an automated milking system (AMS) and to describe the farm-level housing, management, and nutritional risk factors associated with increased farm-average milk BHB and the within-herd HKL prevalence in the first 45 DIM. Canadian AMS farms (n = 162; eastern Canada, n = 8; Quebec, n = 24; Ontario, n = 75; western Canada n = 55) were visited once between April and September 2019 to record housing and herd management practices. The first test milk data for each cow under 45 DIM were collected, along with the final test of the previous lactations for all multiparous cows, from April 1, 2019, to September 30, 2020. The first test milk BHB was then used to classify each individual cow as having or not having HKL (milk BHB ≥0.15 mmol/L) at the time of testing. Milk fat and protein content, milk BHB, and HKL prevalence were summarized by farm and lactation group (all, primiparous, and multiparous). During this same time period, formulated diets for dry and lactating cows, including ingredients and nutrient composition, and AMS milking data were collected. Data from the AMS were used to determine milking behaviors and milk production of each herd during the first 45 DIM. Multivariable regression models were used to associate herd-level housing, feeding management practices, and formulated nutrient composition with first test milk BHB concentrations and within-herd HKL levels separately for primiparous and multiparous cows. The within-herd HKL prevalence for all cows was 21.8%, with primiparous cows having a lower mean prevalence (12.2 ± 9.2%) than multiparous cows (26.6 ± 11.3%). Milk BHB concentration (0.095 ± 0.018 mmol/L) and HKL prevalence for primiparous cows were positively associated with formulated prepartum DMI and forage content of the dry cow diet; however, they were negatively associated with formulated postpartum DMI, the major ingredient in the concentrate supplemented through the AMS, and the partially mixed ration to AMS concentrate ratio. Multiparous cows' milk BHB concentration (0.12 ± 0.023 mmol/L) and HKL prevalence were positively associated with the length of the previous lactation, milk BHB at dry-off, prepartum diet nonfiber carbohydrate content, and the major forage fed on farm, while tending to be negatively associated with feed bunk space during lactation. This study is the first to determine the farm-level risk factors associated with herd-level prevalence of HKL in AMS dairy herds. The results may help to optimize management and guide diet formulation and thus promote the reduction of HKL prevalence.

In this work, the CuAgZr metallic glasses (MGs) are investigated, a promising material for biomedical applications due to their high strength, corrosion resistance, and antibacterial activity. Using an integrated approach of combinatorial synthesis, high-throughput characterization, and machine learning (ML), the mechanical properties of CuAgZr MGs are efficiently explored. The investigation find that post-deposition oxidation in inter-columnar regions with looser packing causes high oxygen content in Cu-rich regions, significantly affecting the alloys mechanical behavior. The study also reveals that nanoscale structural features greatly impact plastic yielding and flow in the alloys. ML algorithms are tested, and the multi-layer perceptron algorithm produced satisfactory predictions for the alloys hardness of untested alloys, providing valuable clues for future research. The work demonstrates the potential of using combinatorial synthesis, high-throughput characterization, and ML  techniques to facilitate the development of new MGs with improved strength and economic feasibility.

Summary: Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health. Methods: We conducted a retrospective cohort study of individuals

Summary: Background: The impact of pre-infection vaccination on the risk of long COVID remains unclear in the pediatric population. We aim to assess the effectiveness of BNT162b2 on long COVID risks with various strains of the SARS-CoV-2 virus in children and adolescents, using comparative effectiveness methods. We further explore if such pre-infection vaccination can mitigate the risk of long COVID beyond its established protective benefits against SARS-CoV-2 infection using causal mediation analysis. Methods: We conducted real-world vaccine effectiveness study and mediation analysis using data from twenty health systems in the RECOVER PCORnet electronic health record (EHR) Program. Three independent cohorts were constructed including adolescents (12–20 years) during the Delta phase (July 1–November 30, 2021), children (5–11 years) and adolescents (12–20 years) during the Omicron phase (January 1–November 30, 2022). The intervention is first dose of the BNT162b2 vaccine in comparison with no receipt of COVID-19 vaccine. The outcomes of interest include conclusive or probable diagnosis of long COVID following a documented SARS-CoV-2 infection, and body-system-specific condition clusters of post-acute sequelae of SARS-CoV-2 infection (PASC), such as cardiac, gastrointestinal, musculoskeletal, respiratory, and syndromic categories. The effectiveness was reported as (1-relative risk)∗100 and mediating effects were reported as relative risks. Findings: 112,590 adolescents (88,811 vaccinated) were included in the cohort for the analysis against Delta variant, and 188,894 children (101,277 vaccinated), and 84,735 adolescents (37,724 vaccinated) were included for the analysis against Omicron variant. During the Delta period, the estimated effectiveness of the BNT162b2 vaccine against long COVID among adolescents was 95.4% (95% CI: 90.9%–97.7%). During the Omicron phase, the estimated effectiveness against long COVID among children was 60.2% (95% CI: 40.3%–73.5%) and 75.1% (95% CI: 50.4%–87.5%) among adolescents. The direct effect of vaccination, defined as the effect beyond their impact on SARS-CoV-2 infections, was found to be statistically non-significant in all three study cohorts, with estimated relative risk of 1.08 (95% CI: 0.75–1.55) in the Delta study among adolescents, 1.24 (95% CI: 0.92–1.66) among children and 0.91 (95% CI: 0.69–1.19) among adolescents in the Omicron studies. Meanwhile, the estimated indirect effects, which are effects through protecting SARS-CoV-2 infections, were estimated as 0.04 (95% CI: 0.03–0.05) among adolescents during Delta phase, 0.31 (95% CI: 0.23–0.42) among children and 0.21 (95% CI: 0.16–0.27) among adolescents during the Omicron period. Interpretation: Our study suggests that BNT162b2 was effective in reducing risk of long COVID outcomes in children and adolescents during the Delta and Omicron periods. The mediation analysis indicates the vaccine’s effectiveness is primarily derived from its role in reducing the risk of SARS-CoV-2 infection. Funding: National Institutes of Health.

Traditional methods to monitor free-range cattle, such as breeding beef bulls, are time-consuming. However, most current remote monitoring technologies operate at high sampling rates, making their use on bulls impractical due to their high battery consumption. Therefore, this study aims to describe and evaluate a machine-learning framework to predict the behaviors of beef bulls from raw accelerometer data at low sampling rates. Collars with 3D-accelerometers were deployed on 33 bulls, recording accelerometer data at 0.5 Hz (22 bulls in 2020 and 2021) or 1.0 Hz (11 bulls in 2023). Videos of bulls in pens, synched with the accelerometer by time, were recorded and analyzed. The behaviors investigated were grazing (GR), resting (RE), ruminating (RU), walking (WA), and in 2023, fighting (FI). Primary labels of activity (AC), corresponding to GR, WA, and FI, and non-activity (NA), corresponding to RE and RU, were assigned. Two datasets were created from data sampled at 1.0 Hz and 0.5 Hz. Then, behavioral events with duration within the inferior 0.05 quantile of the distribution for each behavior were removed, integrated measures of motion were calculated, and segmentation into consecutive 20 s time-windows was performed. Afterward, 132 frequency and time-domain features were extracted, and bulls’ ages were added as a physical feature. Two bulls from each year and dataset were segregated to form independent test sets. A leave-one-animal-out cross-validation (LOAO) was applied to Extratree classifiers to select relevant features. The final classifier was built in a hierarchical structure using XGBoost classifiers to make predictions on two levels: (1) distinguishing between AC and NA, and (2) categorizing AC into GR, WA, FI, and NA into RE or RU. This model was evaluated using LOAO and test sets for each dataset, and precision and sensitivity were calculated for each behavior. Matthews Correlation (MCC) and Cohen's Kappa (CK) coefficients were calculated for the overall assessment of the models’ levels. Comparisons of metrics obtained on LOAO and test sets were performed using the Wilcoxon Sum Rank and the Wilcoxon Signed Rank test. The LOAO MCC for 1.0 Hz (1st level = 0.98 ± 0.01, 2nd level = 0.92 ± 0.02) was higher than 0.5 Hz (1st level = 0.83 ± 0.20, 2nd level = 0.71 ± 0.20). In 1.0 Hz, all behaviors presented mean precision and sensitivity above 0.7, except the sensitivity of FI (LOAO = 0.47 ± 0.06, test set = 0.63 ± 0.18). In 0.5 Hz, the exception was the sensitivity of WA (LOAO = 0.58 ± 0.28, test set = 0.68 ± 0.06) and the sensitivity of RU in the test set (0.54 ± 0.26). Therefore, the proposed framework can be used to predict the behaviors of beef bulls from accelerometers sampling at 0.5 Hz or 1.0 Hz, although better results are observed at 1.0 Hz. Caution should be exercised for predicting FI at 1.0 Hz and WA at 0.5 Hz.

ABSTRACT: The objective of this study was to describe the nutritional strategies used on Canadian dairy farms with automated milking systems (AMS), both at the feed bunk and the concentrate offered at the AMS, as well as to determine what dietary components and nutrients, as formulated, were associated with milk production and milking behaviors on those farms. Formulated diets (including ingredients and nutrient content) and AMS data were collected from April 1, 2019, until September 30, 2020, on 160 AMS farms (eastern Canada [East] = 8, Ontario [ON] = 76, Quebec [QC] = 22, and western Canada [West] = 54). Both partial mixed ration (PMR) and AMS concentrate samples were collected from May 1 to September 30, 2019, on 169 farms (East = 12, ON = 63, QC = 42, West = 52). We collected AMS milking data for 154 herds. For each farm (n = 161), milk recording data were collected and summarized by farm to calculate average milk yield and components. Multivariable regression models were used to associate herd-level formulated nutrient composition and feeding management practices with milk production and milking behavior. Milk yield (mean ± SD = 37.0 ± 0.3 kg/d) was positively associated with the PMR ether extract (EE) concentration (+0.97 kg/d per percentage point [p.p.] increase) and with farms that fed barley silage as their major forage source (n = 16; +2.18 kg/d) as compared with haylage (n = 42), whereas farms that fed corn silage (n = 96; +1.23 kg/d) tended to produce more milk than farms that fed haylage. Greater milk fat content (4.09 ± 0.28%) was associated with a greater PMR-to-AMS concentrate ratio (+0.02 p.p. per unit increase) and total diet net energy for lactation (+0.046 p.p. per 0.1 Mcal/kg increase), but a lesser percentage of NFC of the PMR (−0.016 p.p. per p.p. increase of NFC percentage). Milk protein content (3.38 ± 0.14%) was positively associated with the forage percentage of the PMR (+0.003 p.p. per p.p. increase of forage percentage) and the total diet starch percentage (+0.009 p.p. per p.p. increase of starch percentage), but was negatively associated with farms feeding corn silage (−0.1 p.p. compared with haylage) as their major forage. Greater milking frequency (2.77 ± 0.40 milkings/d) was observed on farms with free-flow cow traffic systems (+0.62 milkings/d) and was positively associated with feed push-up frequency (+0.013 milkings/d per additional feed push-up), but negatively associated with PMR NFC content and forage percentage of the total ration (−0.017 milkings/d per p.p. increase of forage percentage). Lastly, greater milking refusal frequency (1.49 ± 0.82 refusals/d) was observed on farms with free-flow cow traffic systems (+0.84 refusals/d) and farms feeding barley silage (+0.58 refusals/d) than with guided flow and farms feeding either corn silage or haylage, respectively. These data give insight into the ingredients, nutrient formulations and type of diets fed on AMS dairy farms across Canada and the association of those factors with milk production and milking behaviors.

In North American beef production, handling and restraint of young calves is integral to animal welfare and management practices. This study used a mixed-method approach to gather public perceptions of three handling and restraint methods common in western Canada during spring processing (TT—tilt table, RW—roping and wrestling, and NF—roping and NordFork). Canadians (n = 551) participated in an online survey that included videos of each handling method to ascertain preferences and acceptability. Participants were given industry information about handling and restraint or generic information regarding hay as a control information statement within the topic of agriculture. The survey also collected information about knowledge of the beef industry, animal welfare, and empathy toward animals. The reasons for preferences for specific handling methods were described as the presence of a perceived positive attribute and the absence of a perceived negative for most preferred methods, and inversely when explaining the least preferred method. The main themes focused on the calf’s experience, perception of handler actions, and pragmatic balancing of needs for a good life for the calf. All methods were rated as more acceptable for participants that ate meat consistently, knew more about the beef industry, and, to a lesser extent, if the individual had a lower animal empathy score. Acceptability was not affected by providing information about the practices; however, information did elicit more pragmatic reasoning. Most participants preferred TT over NF and RW (p < 0.001) and found TT more acceptable as well (p < 0.001). The TT was the most preferred method due to calf experience and human handling—notably the absence of dragging a calf, which was predominant in why participants selected NF or RW as their least preferred method. Consistency of themes highlights that regardless of method or acceptability, the fundamental expectation of the public focuses on the perception of the calf’s quality of life, humane handling, and pragmatism, which are values aligned with beef sustainability initiatives.

ABSTRACT Most foodborne salmonellosis outbreaks are linked to agricultural animal products with a few serovars accounting for most Salmonella isolated from specific animal products, suggesting an adaptation to the corresponding animal hosts and their respective environments. Here, we utilized whole-genome sequence (WGS) data to analyze the evolution and population genetics of seven serovars frequently isolated from ground beef (Montevideo, Cerro, and Dublin), chicken (Kentucky, Infantis, and Enteritidis), and turkey (Reading) in the United States. In addition, publicly available metadata were used to characterize major clades within each serovar with regard to public health significance. Except for Dublin, all serovars were polyphyletic, comprising 2–6 phylogenetic groups. Further partitioning of the phylogenies identified 25 major clades, including 12 associated with animal or environmental niches. These 12 clades differed in evolutionary parameters (e.g., substitution rates) as well as public health relevant characteristics (e.g., association with human illness, antimicrobial resistance). Overall, our results highlight several critical trends: (i) the Salmonella generation time appears to be more dependent on source than serovar and (ii) all serovars contain clades and sub-clades that are estimated to have emerged after the year 1940 and that are enriched for isolates associated with humans, agricultural animals, antimicrobial resistance (AMR), and/or specific geographical regions. These findings suggest that serotyping alone does not provide enough resolution to differentiate isolates that may have evolved independently, present distinct geographic distribution and host association, and possibly have distinct public health significance.IMPORTANCENon-typhoidal Salmonella are major foodborne bacterial pathogens estimated to cause more than one million illnesses, thousands of hospitalizations, and hundreds of deaths annually in the United States. More than 70% of Salmonella outbreaks in the United States have been associated with agricultural animals. Certain serovars include persistent strains that have repeatedly contaminated beef, chicken, and turkey, causing outbreaks and sporadic cases over many years. These persistent strains represent a particular challenge to public health, as they are genetically clonal and widespread, making it difficult to differentiate distinct outbreak and contamination events using whole-genome sequence (WGS)-based subtyping methods (e.g., core genome allelic typing). Our results indicate that a phylogenetic approach is needed to investigate persistent strains and suggest that the association between a Salmonella serovar and an agricultural animal is driven by the expansion of clonal subtypes that likely became adapted to specific animals and associated environments.

n/aImproving Emergency Medicine ResidentOphthalmologic Management Skills via Simulation

It is critical to sustain the diversity of the microbiota to maintain host homeostasis and health. Growing evidence indicates that changes in gut microbial biodiversity may be associated with the development of several pathologies, including type 2 diabetes mellitus (T2DM). Metformin is still the first-line drug for treatment of T2DM unless there are contra-indications. The drug primarily inhibits hepatic gluconeogenesis and increases the sensitivity of target cells (hepatocytes, adipocytes and myocytes) to insulin; however, increasing evidence suggests that it may also influence the gut. As T2DM patients exhibit gut dysbiosis, the intestinal microbiome has gained interest as a key target for metabolic diseases. Interestingly, changes in the gut microbiome were also observed in T2DM patients treated with metformin compared to those who were not. Therefore, the aim of this review is to present the current state of knowledge regarding the association of the gut microbiome with the antihyperglycemic effect of metformin. Numerous studies indicate that the reduction in glucose concentration observed in T2DM patients treated with metformin is due in part to changes in the biodiversity of the gut microbiota. These changes contribute to improved intestinal barrier integrity, increased production of short-chain fatty acids (SCFAs), regulation of bile acid metabolism, and enhanced glucose absorption. Therefore, in addition to the well-recognized reduction of gluconeogenesis, metformin also appears to exert its glucose-lowering effect by influencing gut microbiome biodiversity. However, we are only beginning to understand how metformin acts on specific microorganisms in the intestine, and further research is needed to understand its role in regulating glucose metabolism, including the impact of this remarkable drug on specific microorganisms in the gut.

In this study, we analyzed the phytosociological data from four sample sites located in the Pannonian region. The study areas, ranging from 2.4 to 2.5 hectares, have been subjected to goat grazing and mowing for 24 years. N1: Nagyréde, an overgrazed pasture with 24 goats; N2: Nagyréde, a mown field; C1: Csokvaomány, a lightly grazed pasture with 12 goats; and meadow C2: Csokvaomány, a site that is both mown and grazed. Six phytosociological surveys were conducted randomly in each area. We also considered the conservation value, biomass production, and forage values. Phytosociological data were processed using hierarchical cluster analysis and the non-parametric Kruskal–Wallis test. The overgrazed pasture (N1) exhibited the most degraded vegetation community, dominated by weeds and disturbance-tolerant species. The overgrazed (N1) pasture had a low forage value because of the different timing of treatments. Even in the lightly grazed pasture (C1), the proportion of species indicative of degradation was significant. The species composition of the areas indicated that the mown and subsequently grazed area (C2) had outstanding values. The species richness of C2 was twice that of the mown field (N2). Based on the present study, a combination of light grazing pressure and mowing is the most suitable approach for managing and economically utilizing these grasslands.

Our study examined the impact of grazing by Hungarian Grey cattle on plant communities in grasslands restored and established through different methods. The grasslands were established and restored in 2009 using five methods: (I) naturally regenerating fallow, (II) hay-mulch addition, (III) seeded grassland following soil preparation, (IV) grazing on abandoned alfalfa fields, and (V) overseeded fallow initiated in 1989. From 2009 to 2011, all sites were uniformly mowed, after which they were grazed using free-ranging Hungarian Grey cattle starting in 2012. This project aims to restore traditional land use and dry grassland grazing in the region. Phytosociological recordings were conducted in 2012, the first year following grazing initiation, and again in 2020, nine years later. We assessed the botanical composition and grassland management value across sites in a 260-hectare experimental area within the Pannonian biogeographic region. The current study seeks to determine how different grassland restoration techniques have influenced the botanical composition and grassland management values of pastures and to identify the most suitable restoration methods. Statistical analyses were conducted using R to assess species count differences across four vegetation categories. The results indicate that the overseeded fallow established in 1989 and the hay-mulch addition method were the most effective techniques. Directly seeded grasslands and abandoned alfalfa fields differed most significantly from these areas. Across all types, species richness and total cover increased relative to the initial conditions in 2012, and the naturalness of the species composition also improved. Returning to traditional land use improved the ecological state of all sites. Restoration of the grazed areas proved optimal over the elapsed period, with two years of mowing followed by grazing. Grazing with Hungarian Grey cattle, a low-impact rustic breed, yielded successful grassland restoration outcomes. Among the restoration methods, direct seeding and the use of alfalfa fields proved uneconomical and ineffective in promoting the desired species composition. Natural regeneration and, particularly, the hay-mulch addition method, were the most effective for conservation and grassland management.

Abstract Olaparib is a PARP inhibitor (PARPi) approved for targeted treatment of ovarian cancer (OC). However, its efficacy is impeded by the inevitable occurrence of resistance. Here, we investigated whether the cytotoxic activity of olaparib could be synergistically enhanced in olaparib-resistant OC cells with BRCA2 reversion mutation by the addition of inhibitors of the ATR/CHK1 pathway. Moreover, we provide insights into alterations in the DNA damage response (DDR) pathway induced by combination treatments. Antitumor activity of olaparib alone or combined with an ATR inhibitor (ATRi, ceralasertib) or CHK1 inhibitor (CHK1i, MK-8776) was evaluated in OC cell lines sensitive (PEO1, PEO4) and resistant (PEO1-OR) to olaparib. Antibody microarrays were used to explore changes in expression of 27 DDR-related proteins. Olaparib in combination with ATR/CHK1 inhibitors synergistically induced a decrease in viability and clonogenic survival and an increase in apoptosis mediated by caspase-3/7 in all OC cells. Combination treatments induced cumulative alterations in expression of DDR-related proteins mediating distinct DNA repair pathways and cell cycle control. In the presence of ATRi and CHK1i, olaparib-induced upregulation of proteins determining cell fate after DNA damage (PARP1, CHK1, c-Abl, Ku70, Ku80, MDM2, and p21) was abrogated in PEO1-OR cells. Overall, the addition of ATRi or CHK1i to olaparib effectively overcomes resistance to PARPi exerting anti-proliferative effect in BRCA2 MUT olaparib-resistant OC cells and alters expression of DDR-related proteins. These new molecular insights into cellular response to olaparib combined with ATR/CHK1 inhibitors might help improve targeted therapies for olaparib-resistant OC.

Anna Pajor-&Sacute;wierzy, Katarzyna Kozak, Dorota Duraczy&nacute;ska, Agata Wiertel-Pochopie&nacute;, Jan Zawa&lstrok;a, Krzysztof Szczepanowicz Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Kraków, PolandCorrespondence: Anna Pajor-&Sacute;wierzy, Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Kraków, Poland, Email anna.pajor-swierzy@ikifp.edu.plIntroductions: Ink based on metallic nanoparticles has been widely used so far for the fabrication of electronic circuits and devices using printing technology. This study aimed at the analysis of the effect of the silver shell thickness of nickel@silver core@shell (Ni@Ag) nanoparticles (NPs) on the fabrication and conductive properties of deposited coatings.Methods: The process of the synthesis of Ni@Ag NPs with various silver shell thicknesses was developed. The physicochemical properties (size, stability against aggregation process) of synthesized Ni@Ag nanoparticles were analyzed. The films based on ink containing Ni@Ag NPs with different silver shell thicknesses were fabricated and sintered in a temperature range of 120– 300 °C and at times from 15 to 90 min. The dependence of their conductive properties on the applied temperature and time as well as silver shell thickness was evaluated.Results: Ni NPs were coated with 10, 20, 30, 35, 45, and 55 nm silver shell thickness. The resistivity of coatings based on obtained NPs depends on the thickness of the Ag shell and the sintering temperature. After sintering at 300 °C, the highest decrease in its value (at an optimal sintering time of 60 min) from about 100 μΩ·cm to 9 μΩ·cm was observed when the thickness of the shell increased from 10 to 55 nm. At the lowest sintering temperature (120 °C) the highest conductivity (about 50% of that for bulk nickel) was obtained for films based on Ni@Ag NPs with 45 and 55 nm of the silver shell thickness.Discussions: The analysis of the resistivity of the sintered films showed that higher conductivity was obtained for the coatings formed from Ni@Ag NPs with the thicker Ag shell; moreover, thicker shells allowed a lowering of sintering temperature due to higher conductivity and a lower melting point of silver in comparison to nickel NPs. Keywords: core@shell nanoparticles, the thickness of the silver shell, thermal sintering, conductive properties, metallic coatings

Abstract Multi-system inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection in children, and there is a critical need to unfold its highly heterogeneous disease patterns. Our objective was to characterize the illness spectrum of MIS-C for improved recognition and management. We conducted a retrospective cohort study using data from March 1, 2020–September 30, 2022, in 8 pediatric medical centers from PEDSnet. We included 1139 children hospitalized with MIS-C and used their demographics, symptoms, conditions, laboratory values, and medications for analyses. We applied heterogeneity-adaptive latent class analyses and identified three latent classes. We further characterized the sociodemographic and clinical characteristics of the latent classes and evaluated their temporal patterns. Class 1 (47.9%) represented children with the most severe presentation, with more admission to the ICU, higher inflammatory markers, hypotension/shock/dehydration, cardiac involvement, acute kidney injury and respiratory involvement. Class 2 (23.3%) represented a moderate presentation, with 4–6 organ systems involved, and some overlapping features with acute COVID-19. Class 3 (28.8%) represented a mild presentation. Our results indicated that MIS-C has a spectrum of clinical severity ranging from mild to severe and the proportion of severe or critical MIS-C decreased over time.

Citrate lies at a critical node of metabolism, linking tricarboxylic acid metabolism and lipogenesis via acetyl-coenzyme A. Recent studies have observed that deficiency of the sodium-dependent citrate transporter (NaCT), encoded by SLC13A5, dysregulates hepatic metabolism and drives pediatric epilepsy. To examine how NaCT contributes to citrate metabolism in cells relevant to the pathophysiology of these diseases, we apply 13C isotope tracing to SLC13A5-deficient hepatocellular carcinoma (HCC) cells and primary rat cortical neurons. Exogenous citrate appreciably contributes to intermediary metabolism only under hypoxic conditions. In the absence of glutamine, citrate supplementation increases de novo lipogenesis and growth of HCC cells. Knockout of SLC13A5 in Huh7 cells compromises citrate uptake and catabolism. Citrate supplementation rescues Huh7 cell viability in response to glutamine deprivation or Zn2+ treatment, and NaCT deficiency mitigates these effects. Collectively, these findings demonstrate that NaCT-mediated citrate uptake is metabolically important under nutrient-limited conditions and may facilitate resistance to metal toxicity.

In general, it can be stated that the economics of non-dairy sheep breeding in the Czech Republic experienced a worsening trend in recent years. One of the ways to improve this situation is to use some of these breeds also for milk production. One of the possible breeds usable for milk production, especially for the good milk production of mothers, is the Clun Forest (CF). The aim of our experiment was to evaluate the daily milk yield (DMY) and the contents of fat (F), total protein (TP) and lactose (L), pH, titratable acidity (TA), concentration of urea (CU) and somatic cell count (SCC) in CF ewes during lactation. In our experiment, the following means of individual traits for the whole lactation were found: DMY: 579 g, contents of F, TP and L: 6.73%, 5.82% and 4.98%, pH: 6.55, TA: 8.74 °SH, CU: 36.08 mg/100 ml and log SCC: 4.71. The stage of lactation had a significant (P < 0.01) effect on DMY, contents of F and TP and pH and TA. The results of our experiment show that CF ewes had lower DMY than dairy breeds (DB). However, the majority of the milk quality traits was comparable to DB. Moreover, the high fat and protein contents and the values of most other milk quality traits are good prerequisites for high cheese yield and optimal final quality of other sheep's milk products. The results of our experiment suggest that CF ewes could be used for milk production while the milk production of CF ewes should ensure an improvement in the economics and competitiveness of smaller farms in particular.

Metformin, one of the most frequently used oral glucose-lowering drugs (GLDs), is associated with the occurrence of gastrointestinal (GI) adverse events in approximately 20% of users. These unwanted actions result in non-compliance or even discontinuation of metformin therapy. The aim of the presented meta-analysis was to determine whether adding a drug from the group of sulfonylureas, glitazones, DPP-IV inhibitors, or probiotics to metformin monotherapy may affect the risk of GI side effects. The material for this meta-analysis comprised data from 26 randomized controlled clinical trials (RCTs) published in English. This meta-analysis included 41,048 patients. The PubMed, Cochrane Library, and Clinical Trials databases were thoroughly searched to find relevant RCTs. The Population, Intervention, Comparison, Outcomes, and Study Type (PICOT) structure was used to formulate study selection criteria and the research question. Cochrane Review Manager Software 5.4 was used to carry out analysis of collected data. The results were presented as relative risk (RR) and 95% confidence interval (95% CI) for each group, and p < 0.05 was considered as statistically significant. As expected from clinical practice, metformin was associated with a markedly increased risk of abdominal pain, nausea, and vomiting compared to placebo. In comparison to other GLDs, taking metformin was related to an elevated risk of diarrhea and abdominal pain and to a lowered risk of vomiting and bloating. In turn, adding other GLDs to metformin treatment was associated with an elevated risk of nausea and vomiting than treatment with metformin in monotherapy. However, adding probiotics to metformin therapy was related to a decreased risk of diarrhea, bloating, and constipation. The obtained results demonstrate that the combination of metformin with other GLDs may elevate the risk of nausea and vomiting, whereas combination with probiotics decreases the risk of diarrhea, bloating, and constipation. Thus, the results of our meta-analysis suggest that probiotics may reduce the risk of some GI side effects in people with type 2 diabetes mellitus (T2DM) who started treatment with metformin.

Many farms have been replacing traditional lighting sources with light-emitting diode (LED) bulbs because of technological modernization. We aimed to investigate the effects of incandescent lighting (IL) and LED lighting on Cobb 500 broiler chickens for six weeks. Production parameters (body weight, feed consumption, feed conversion ratio), calculated slaughter values (yield%, relative breast%, thigh%) and breast meat quality parameters (pH at 45 min and 24 h postmortem, color, drip loss, kitchen equipment losses, shear force, meat composition) were recorded. Non-stop recordings were used to analyze the behavior of the birds during several periods of rearing. The LED group was significantly better in the body weight parameter between week 1 and 5 and the feed conversion ratio between week 2 and 3. The most significant difference in behavior was observed in the middle of the rearing period. The chickens in the LED group spent more time eating, drinking and interacting, and rested less. There was no difference in the meat quality parameters; only shear force was significantly lower in the LED group (1781.9 g/s vs. 2098.8 g/s). According to our results, LED lighting can bring about positive changes in animal production efficiency, behavior and other important characteristics for meat consumers.

AbstractEntrepreneurship education, the process of knowledge, skill, competency, and attitude development, aims to maximize the effectiveness of the entrepreneurial capacity building. The pandemic boosted the digital transformation of higher education and brought the online incubation platform NETMIB to life. This paper introduces this unique platform solution and utilizes online opportunities for skill and attitude assessment. An online survey-based research method was applied, and an online Entrepreneurial Orientation (EO) Index was developed as a valid scale for measuring entrepreneurial attitudes in online incubation programs. Based on the findings, student idea owners in the online incubation process have a significantly higher propensity to engage in business activities and a stronger desire for independence and achievement. The findings of this paper can contribute to the targeting and development of educational interventions in the incubation programs, and the online EO Index can be a useful tool among the performance measures of various incubation programs.Summary: Entrepreneurship education, the process of knowledge, skill, competency, and attitude development, aims to maximize the effectiveness of the entrepreneurial capacity building. The pandemic boosted the digital transformation of higher education and brought the online incubation platform NETMIB (Network of multidisciplinary ideation and business model generation) to life. This paper introduces this unique platform solution of online incubation and utilizes online opportunities for skill and attitude assessment. Since education aims to influence entrepreneurial capacity, measured by attitudes, the paper develops a self-assessment tool for online entrepreneurship education. Hypothesizes that there are significant differences in the attitudes of the members according to their role in the online incubation process. An online survey-based research method was used, and an entrepreneurial attitude construct was created concerning the member’s desire for innovation, personal control, achievement, and self-esteem. Based on the findings, student idea owners in the online incubation process have a significantly higher propensity to engage in business activities and a stronger desire for independence and achievement. The findings of this paper contribute to the targeting and development of educational interventions in incubation programs, and the online Entrepreneurial Orientation Index can be a useful tool among the performance measures of various incubation programs.

Abstract In this work, the CuAgZr metallic glasses (MGs) are investigated, a promising material for biomedical applications due to their high strength, corrosion resistance, and antibacterial activity. Using an integrated approach of combinatorial synthesis, high‐throughput characterization, and machine learning (ML), the mechanical properties of CuAgZr MGs are efficiently explored. The investigation find that post‐deposition oxidation in inter‐columnar regions with looser packing causes high oxygen content in Cu‐rich regions, significantly affecting the alloys' mechanical behavior. The study also reveals that nanoscale structural features greatly impact plastic yielding and flow in the alloys. ML algorithms are tested, and the multi‐layer perceptron algorithm produced satisfactory predictions for the alloys' hardness of untested alloys, providing valuable clues for future research. The work demonstrates the potential of using combinatorial synthesis, high‐throughput characterization, and ML techniques to facilitate the development of new MGs with improved strength and economic feasibility.

BackgroundThe clinical and genetic heterogeneity of diffuse large B-cell lymphoma (DLBCL) presents distinct challenges in predicting response to therapy and overall prognosis. The main objective of this study was to assess the application of the immunohistochemistry- and interphase fluorescence in situ hybridization (FISH)-based molecular markers in the diagnosis of DLBCL and its prognostic value in patients treated with rituximab-based immunochemotherapy.MethodsThis is a multicenter, retrospective study, which analyzed data from 7 Hungarian hematology centers. Eligible patients were adults, had a histologically confirmed diagnosis of DLBCL, were treated with rituximab-based immunochemotherapy in the first line, and had available clinicopathological data including International Prognostic Index (IPI). On the specimens, immunohistochemistry and FISH methods were performed. Germinal center B-cell like (GCB) and non-GCB subtypes were classified by the Hans algorithm. Outcomes included overall survival (OS), event-free survival (EFS), and EFS at 2 years (EFS24). For survival analysis, we used Kaplan-Meier curves with the log-rank test and multivariate Cox regression.ResultsA total of 247 DLBCL cases were included. Cases were positive for MYC, BCL2, BCL6, and MUM1 expression in 52.1%, 66.2%, 72.6%, and 77.8%, respectively. BCL6 translocation, BCL2 gene copy number (GCN) gain, IGH::MYC translocation, MYC GCN gain, IGH::BCL2 translocation, and BCL6 GCN gain were detected in 21.4%, 14.1%, 7.3%, 1.8%, 7.3%, and 0.9%, respectively. At a median follow-up of 52 months, 140 patients (56.7%) had disease progression or relapse. The Kaplan-Meier estimate for EFS24 was 56.2% (CI: 50.4–62.8%). In univariate analysis, only IPI and BCL6 expression were significant predictors of both OS and EFS, whereas MUM1 predicted EFS only. In multivariate analysis, the IPI score was a significant independent negative, whereas MIB-1 and BCL6 protein expressions were significant independent positive predictors of both OS and EFS.ConclusionIn our study, we found that only IPI, BCL6 protein expression and MIB-1 protein expression are independent predictors of survival outcomes in DLBCL. We did not find any difference in survival by GCB vs. non-GCB subtypes. These findings may improve prognostication in DLBCL and can contribute to designing further research in the area.

Wood pastures have been characteristic farming types in the Pannonian biogeographical region over the centuries. In the present work, we studied wood-pastures of typical geographical locations in the North Hungarian Mountain Range of Hungary characterized by similar environmental conditions but grazed by different livestock. The sample area of Cserépfalu was grazed by Hungarian Grey Cattle, while the Erdőbénye was grazed by Hungarian Racka Sheep. Coenological records of the sites were collected from 2012 to 2021 in the main vegetation period according to the Braun-Blanquet method with the application of 2 × 2 m sampling quadrats, where the coverage estimated by percentage for each present species was also recorded. To evaluate the state of vegetation, ’ecological ordering’ distribution, diversity, and grassland management values were used. Between the two areas, the grazing pressure of the two studied livestock produced different results. Based on the diversity values, woody–shrubby–grassland mosaic diversity values were high (Shannon diversity: 2.21–2.87). Cattle grazing resulted in a variable and mosaic-like shrubby area with high cover values. Based on our results, grazing by cattle provides an adequate solution for forming and conserving wood-pasture habitats in the studied areas of Hungary. However, if the purpose is to also form valuable grassland with high grassland management values, partly sheep grazing should be suggested.