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The aim of this study was to understand and describe the physiological and biomechanical demands of various tasks used in basketball training and, subsequently, to provide a practical application of these tasks in a typical training week. Twelve basketball players had their external load variables monitored across 179 training sessions (2896 samples) using local positioning system technology. These variables included total distance covered, distance covered at various intensity levels, accelerations, decelerations, PlayerLoad™, and explosive efforts. The analysis revealed significant differences in both physiological and biomechanical loads across various drills. Specifically, tasks with more space and fewer defenders, such as 3v0 full court, impose higher physiological loads compared to tasks with less space and more defenders, like 5v5 full court. The difference in physiological load between these tasks was statistically significant ( p < 0.05) with a moderate effect size (ES: -0.60, 95% CI: [-0.99, -0.22]). In terms of biomechanical load, drills with increased defensive pressure, such as 5v5 full court, exhibited significantly higher values compared to less specific drills, such as 5v0 full court, with a very large effect size (ES: 1.37, 95% CI: [1.04, 1.70], p < 0.01). Additionally, comparisons between 5v5 full court and 3v0 full court for biomechanical load produced a very large effect size (ES: 1.67, 95% CI: [1.37, 1.97], p < 0.01), indicating a substantial difference in load demands. The results indicate that tasks with more space and fewer defenders impose higher physiological loads, while those with less space and more defenders increase the biomechanical load. For training design, it is recommended to schedule tasks with a higher biomechanical load at the beginning of the session and those with a physiological orientation toward the end. Understanding the distinct demands of different drills can help coaches structure training sessions more effectively to optimize player load and performance development throughout the week.

R2R3-MYB transcription factors function as the master regulators of the phenylpropanoid pathway in which both lignin and anthocyanin are produced. In poplar, R2R3-MYB transcription factor PdMYB118 positively regulates anthocyanin production to change leaf color. However, the molecular mechanism by which it controls different branches of the phenylpropanoid pathway still remains poorly understood. Here, we reported that in addition to anthocyanin synthesis, lignin deposition and xylem differentiation were regulated by PdMYB118 through inhibiting PagKNAT2/6b gene expression. The transgenic poplar plants overexpressing PdMYB118 accumulated more xylem, lignin and anthocyanin. Transcriptome and reverse transcription quantitative PCR analyses revealed that the expression of PagKNAT2/6b gene which inhibited lignin deposition and xylem differentiation was significantly down-regulated in transgenic poplar plants. Subsequent dual-luciferase reporter and yeast-one-hybrid assays demonstrated that PdMYB118 directly inhibited the transcription of PagKNAT2/6b by binding to the AC elements in its promoter region. Further experiments with transgenic poplar plants overexpressing PagKNAT2/6b demonstrated that overexpression of PagKNAT2/6b in the PdMYB118 overexpression background rescued lignin accumulation and xylem width to the same level of wild type plants. The findings in this work suggest that PdMYB118 is involved in the lignin deposition and xylem differentiation via modulating the expression of PagKNAT2/6b, and the PdMYB118- PagKNAT2/6b model can be used for the genetic breeding of new woody tree with high lignin production., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aptamers are often employed as molecular recognition elements in the development of different types of biosensors. Many of these biosensors take advantage of the aptamer having a ligand-induced structure-formation binding mechanism. However, this binding mechanism is poorly understood. Here we use isothermal titration calorimetry, circular dichroism spectroscopy and NMR spectroscopy to study the binding and ligand-induced structural change exhibited by a dopamine-binding DNA aptamer. We analysed a series of aptamers where we shorten the terminal stem that contains the 5' and 3' termini of the aptamer sequence. All aptamers bind dopamine in an enthalpically driven process coupled with an unfavorable entropy. A general trend of the aptamer having a weaker binding affinity is observed as the terminal stem is shortened. For all aptamers studied, numerous signals appear in the imino region of the 1 H NMR spectrum indicating that new structure forms with ligand binding. However, it is only when this region of structure formation in the aptamer is brought close to the sensor surface that we obtain a functional electrochemical aptamer-based biosensor., (© 2024 The Author(s). ChemBioChem published by Wiley-VCH GmbH.)

Background: The psychological well-being of nurses, during the COVID-19 pandemic has become a critical area of concern. This study examines the psychological impact of the pandemic on nurses, focusing on the mediating role of perceived social distance between work units and depression., Methods: This study employed a cross-sectional design with respondent driven sampling. Anonymous questionnaire consisting of demographics, perceived social distancing and depression were distributed through email, Facebook, LINE, and other online platforms by key informants of nurses. A total of 1,064 volunteered questionnaires were collected, consisting of 1,032 females and 32 males., Results: Data showed that 517 (48.9%) nurses may have depression. Results from the structure equation modeling indicated that perception of social distancing mediates between individuals in units of care and depression, while unit and tenure of nursing work were negatively associated with depression., Conclusion: The study findings support that perceived social distancing due to COVID-19 pandemic from others toward nurses may have influential impact on elevated depression, especially for nurses worked in the acute critical care. Thus, emotional support should be emphasized, and avenues for stress relief should be provided as well as creating a supportive workplace environment is crucial to nurses and patient safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Lee and Chao.)

Prior studies have suggested the existence of reduced penetrance pathogenic variants (RPPVs) in BRCA1 and BRCA2 (BRCA) which pose challenges for patient counseling and care. Here, we sought to establish RPPVs as a new category of variants. Candidate BRCA RPPVs provided by two large clinical diagnostic laboratories were compiled to identify those with the highest likelihood of being a RPPV, based on concordant interpretations. Sixteen concordant candidate BRCA RPPVs across both laboratories were systematically assessed. RPPVs included missense, splice site, and frameshift variants. Our study establishes RPPVs as a new class of variants imparting a moderately increased risk of breast cancer, which impacts risk-informed cancer prevention strategies, and provides a framework to standardize interpretation and reporting of BRCA RPPVs. Further work to define clinically meaningful risk thresholds and categories for reporting BRCA RPPVs is needed to personalize cancer risks in conjunction with other risk factors., (© 2024. The Author(s).)

This study aimed to (i) compare the extent of home-court advantage (HA) and home win percentage (HW) between Spanish basketball leagues across different playing levels (i.e., leagues) and (ii) analyze the influence of team ability on HA and HW within each playing level. We gathered data for game locations and results from open online sources for all games in the First Division (ACB), Second Division (LEB Gold), and Third Division (LEB Silver) Spanish male basketball leagues between 2010-2023. The dataset included 12 seasons, 635 teams (215 First Division, 203, Second Division, and 217 Third Division), and 19,539 games (7075 First Division, 6344 Second Division, and 5520 Third Division). We calculated HA [(total home wins/total wins) * 100] and HW [(total home wins/total home games) * 100] for each team across each season. We performed Kruskal Wallis tests, calculated partial eta squared ( η p 2 ), and performed Mann-Whitney U tests with rank biserial correlation ( r b ) effect sizes and Dwass-Steel-Critchlow-Fligner pairwise comparisons to compare HA and HW between leagues and between team abilities (low, medium, and/or high) within each league. There was a significant effect for HA between leagues ( p = .01) with post hoc comparisons revealing a higher HA for the First Division than for the Third Division ( p = .01), but HW was not significantly different between leagues. In turn, variations in HA and HW between team abilities were consistent across playing levels, with HW significantly increasing in a progressive manner with higher team abilities ( p < .001) and with HA significantly lower among high-level teams compared to lower-ability team clusters ( p < .01). These findings emphasize the importance of considering playing level and team ability and interpreting HA and HW together to contextualize an apparent home advantage in Spanish basketball.

Background: Treatment delivery safety and accuracy are essential to control the disease and protect healthy tissues in radiation therapy. For usual treatment, a phantom-based patient specific quality assurance (PSQA) is performed to verify the delivery prior to the treatment. The emergence of adaptive radiation therapy (ART) adds new complexities to PSQA. In fact, organ at risks and target volume re-contouring as well as plan re-optimization and treatment delivery are performed with the patient immobilized on the treatment couch, making phantom-based pretreatment PSQA impractical. In this case, phantomless PSQA tools based on multileaf collimator (MLC) leaf open times (LOTs) verifications provide alternative approaches for the Radixact® treatment units. However, their validity is compromised by the lack of independent and reliable methods for calculating the LOT performed by the MLC during deliveries., Purpose: To provide independent and reliable methods of LOT calculation for the Radixact® treatment units., Methods: Two methods for calculating the LOTs performed by the MLC during deliveries have been implemented. The first method uses the signal recorded by the build-in detector and the second method uses the signal recorded by optical sensors mounted on the MLC. To calibrate the methods to the ground truth, in-phantom ionization chamber LOT measurements have been conducted on a Radixact® treatment unit. The methods were validated by comparing LOT calculations with in-phantom ionization chamber LOT measurements performed on two Radixact® treatment units., Results: The study shows a good agreement between the two LOT calculation methods and the in-phantom ionization chamber measurements. There are no notable differences between the two methods and the same results were observed on the different treatment units., Conclusions: The two implemented methods have the potential to be part of a PSQA solution for ART in tomotherapy., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

This study aimed to compare the most demanding scenarios (MDS) of under-19 professional soccer players during official matches, controlling for contextual factors such as playing position, the level of opponent teams, playing venue, match status, playing surface, pitch size, and playing status of players. A total of 42 players were monitored across 27 games using Global Positioning System (GPS) technology to collect the external loads, including total distance covered, high-speed running, sprint distance, accelerations, and decelerations. MDS were calculated across 1-minute, 5-minute, and 10-minute time windows for each variable. Significant differences were found based on the contextual factors. (i) Opponent level did not show significant differences; (ii) full-backs covered more distance at 1 minute in home games; (iii) midfielders in winning vs. drawing scenarios exhibited higher decelerations at 1 minute but less distance at 10 minutes; (iv) in drawing vs. losing scenarios, central defenders had greater distance at 5 minutes and accelerations at 5 minutes, while midfielders showed greater distances at 1 minute, 5 minutes, and 10 minutes; (v) offensive midfielders and forwards displayed specific performance differences; (vi) no significant differences were found for the playing surface; (vii) regarding pitch size, full-backs covered more distance at 5 minutes on larger pitches, while midfielders covered more distance at 5 minutes and 10 minutes; and (viii) starters generally outperformed non-starter players across various variables depending on the playing positions. The findings suggest that contextual factors have a significant impact on soccer player performance across different playing positions., Competing Interests: The authors declared no conflict of interest., (Copyright © Institute of Sport – National Research Instutite.)

LESION SIMULATING DISEASE1 (LSD) family genes play a key role in plant response to abiotic and biotic stress. However, their functions in the resistance of tree to drought stress are still largely not clear. Here, five LSD family genes in poplar genome were identified. Phylogenetic and collinear relationship analysis showed that they belonged to LSD, LSD-one-like 1 (LOL1) and LSD-one-like 2 (LOL2) subfamilies, and experienced two segmental duplication events. PagLSDs were highly conserved in gene structure, and all PagLSDs contained at least two LSD domains. Expression pattern and cis-acting element analyses showed that PagLSDs were widely expressed in different organs, significantly induced by polyethylene glycol, and possessed a great number of plant growth, development, plant hormones, and biotic and abiotic stress elements in their promoter regions. Further physiological experiments with transgenic poplar plants revealed that overexpression of PagLOL1b significantly enhanced the drought tolerance of transgenic plants. The improved drought tolerance was closely associated with the significant increase in stomatal closure, water use efficiency, antioxidant enzyme gene expression and antioxidant enzyme activity in transgenic plants. The results in our study imply that PagLOL1b has great potential in the engineering of new tree varieties resistant to drought stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The purpose of this study was to identify the external demands during official under-18 basketball matches that included four quarters (Q1, Q2, Q3, Q4) and/or overtime (OT) periods. Variables included: 1) distance covered and distance covered within four intensity zones (standing-walking S-W, jogging JOG, running RUN, and high-speed running HSR); 2) explosive efforts per minute (EEs); 3) PlayerLoad (PL); 4) the number of jumps per minute; 5) the number of accelerations above 2 m·s2 (ACCs); and 6) the number of decelerations above -2 m·s2 per minute (DECs). The values for total distance, JOG, RUN, HSR, PL, ACC, and DEC were significantly smaller during periods Q2, Q3, Q4, and OT compared to Q1. In addition, the number of EEs during Q1 was significantly greater than during Q3, Q4, and OT. When comparing OT periods to Q2, there were significantly smaller values for total distance, RUN, and PL. Similarly, when comparing OT periods to Q3, significantly smaller values were found for PL. Furthermore, when comparing OT periods to Q4, significantly smaller values were achieved for total distance and PL. These findings indicate that players experienced a decrease in external physical demands as the match progressed to an OT period. This decrease may be indicative of player fatigue and/or strategic changes that should be considered by practitioners in the preparation and management of players for overall team success in junior basketball competitions., Competing Interests: The authors declare no conflict of interest., (Copyright: © Academy of Physical Education in Katowice.)

Consideration of workload intensity and peak demands across different periods of basketball games contributes to understanding the external physical requirements of elite basketball players. Therefore, the aim of this study was to investigate the average intensity and peak demands encountered by players throughout game quarters. PlayerLoad per minute and PlayerLoad at three different time samples (30 s, 1 min, and 3 min) were used as workload metrics. A total of 14 professional elite male basketball players were monitored during 30 official games to investigate this. A linear mixed model and Cohen's d were employed to identify significant differences and quantify the effect sizes among game quarters. The results showed a significant, moderate effect in PlayerLoad per minute between Q1 vs. Q4, and a small effect between Q2 and Q3 vs. Q4. Furthermore, a small to moderate decline was observed in external peak values for PlayerLoad across game quarters. Specifically,, a significant decrease was found for the 3 min time window between Q1 and other quarters. The findings from the present study suggest that professional basketball players tend to experience fatigue or reduced physical output as the game progresses.

Key Message: 63 L. bicolor WRKY genes were identified and their informatics was analyzed. The results suggested that the LbWRKY genes involved in the development and salt secretion of salt glands in L. bicolor. Salt stress, as a universal abiotic stress, severely inhibits the growth and development of plants. WRKY transcription factors play a vital role in plant growth and development, as well as in response to various stresses. Nevertheless, little is known of systematic genome-wide analysis of the WRKY genes in Limonium bicolor, a model recretohalophyte. In this study, 63 L. bicolor WRKY genes were identified (LbWRKY1-63), which were unevenly distributed across seven chromosomes and one scaffold. Based on the structural and phylogenetic characteristics, 63 LbWRKYs are divided into three main groups. Cis-elements in the LbWRKY promoters were related to growth and development, phytohormone responses, and stress responses. Colinearity analysis showed strong colinearity between LbWRKYs and GmWRKYs from soybean (Glycine max). Therefore, LbWRKY genes maybe have similar functions to GmWRKY genes. Expression analysis showed that 28 LbWRKY genes are highly expressed in roots, 9 in stems, 26 in leaves, and 12 in flowers and most LbWRKY genes responded to NaCl, ABA, and PEG6000. Silencing LbWRKY10 reduced salt gland density and salt secretion ability of leaves, and the salt tolerance of the species. Consistent with this, genes associated with salt gland development were markedly down-regulated in the LbWRKY10-silenced lines. Our findings suggested that the LbWRKY genes involved in the development and salt secretion of salt glands in L. bicolor. Our research provides new insights into the functions of the WRKY family in halophytes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Our main aim in this study was to analyze any differences in Win Percentages at Home (HW) that might represent a Home-Court Advantage (HA) in women's professional basketball. A secondary objective was to analyze how team ability might modify the HA effect by comparing any interaction effect between HW and team ability in games played with and without fans. We collected data from first Spanish female basketball divisions, using a linear mixed model (LMM) for repeated measures to identify differences between time periods (games with fans vs. games without fans) for HA and HW. When comparing games with and without fans, we found no significant HA and HW differences ( p = .283 and p = .872, respectively). In fact, interestingly, we observed higher win values when fans were absent. Additionally, during the COVID-19 shut down stage, HA increased; but it returned to pre-pandemic levels afterward, with no significant differences between these periods ( p = .482). Similarly, while HW seemed to increase during the COVID-19 shut down period and continued improving in the post-pandemic phase, there were actually no statistically significant differences ( p = .772). Higher HA and HW were evident without fans during the pandemic compared to the pre-pandemic period when fans were present in women's professional basketball. During the post-pandemic period, HA decreased upon fans' return, while HW continued increasing. We discuss possible bases for these unexpected findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study examined the frequency of the most demanding scenarios (MDS) during official soccer matches using rolling averages over 1, 5, and 10 min. Forty-two Under-19 players from different positions (central defenders, full-backs, central midfielders, wide midfielders, offensive midfielders, and forwards) were monitored across 27 matches using GPS to track distance covered, high-speed running, sprint distance, accelerations, and decelerations. Intensity thresholds were established based on percentiles (0-25, 25-50, 50-75, 75-100, and ≥100). The main findings suggest that: (i) Peak Demands occur in less than 1% of all time windows and variables for all positions; (ii) Most efforts occur below peak demands, with around 95% for high-speed running and sprint distance, and 85% for accelerations, decelerations, and total distance; (iii) Significant differences in intensity distributions were found between positions, particularly at medium-low and high intensities. Regarding training prescription, relying solely on MDS may be limited, highlighting the need to supplement MDS with other metrics for a comprehensive understanding of match demands. This approach ensures better-informed training programs for soccer players.

Low concentration strontium (LC-Sr) can promote the growth of plants. In order to explore its promoting mechanism from the aspect of photosynthesis, the leaf characteristics, CO 2 assimilation and chlorophyll (Chl) a fluorescence kinetics were investigated with hydroponically LC-Sr-treated Chinese cabbage seedlings. After a 28-d treatment to SrCl 2 at different concentrations (0.1, 0.2, 0.5, and 1.0 mmol L -1 ), we observed an increase in the specific leaf weight (SLW) of Chinese cabbage compared with the control group. Notably, as the strontium concentration increased, a more pronounced improvement trend in the contents of Chl and protein in the leaves was observed, contributing to the enhancement of photosynthesis. However, the statistical differences in P n among various LC-Sr treatments were not significant. Nevertheless, the leaf starch content exhibited a significant increase after LC-Sr treatments. Additionally, Chl a fluorescence transient has been used as a sensitive indicator of the promotional effect of LC-Sr on photosynthesis. The results of fluorescence parameters showed that LC-Sr treatments accelerated the light reaction speed of leaves (T fm , dV/dt o , dVG/dt o ), improved the energy utilization efficiency of photosystem (PSI and PSII) (ETo/CSo, ψ ET ,ψ RE , δ Ro , φ Ro ), and ultimately enhanced the photosynthetic performance of leaves (PI abs , SFI abs , DF abs ). The increased RCs/CSo and Sm contributed to the enhancement of the light reaction activity of strontium-treated leaves. The LC-Sr treatments had no interference with the calcium absorption, and notably enhanced the photosynthetic capacity of Chinese cabbage, shedding light on potential benefits of LC-Sr for crop cultivation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Patients with germline pathogenic variants (PVs) in APC develop tens (attenuated familial adenomatous polyposis [AFAP]) to innumerable (classic FAP) adenomatous polyps in their colon and are at significantly increased lifetime risk of colorectal cancer. Up to 10% of FAP and up to 50% of patients with AFAP who have undergone DNA-only multigene panel testing (MGPT) do not have an identified PV in APC . We seek to demonstrate how the addition of RNA sequencing run concurrently with DNA can improve detection of germline PVs in individuals with a clinical presentation of AFAP/FAP., Methods: We performed a retrospective query of individuals tested with paired DNA-RNA MGPT from 2021 to 2022 at a single laboratory and included those with a novel APC PV located in intronic regions infrequently covered by MGPT, a personal history of polyposis, and family medical history provided. All clinical data were deidentified in this institutional review board-exempt study., Results: Three novel APC variants were identified in six families and were shown to cause aberrant splicing because of the creation of a deep intronic cryptic splice site that leads to an RNA transcript subject nonsense-mediated decay. Several carriers had previously undergone DNA-only genetic testing and had received a negative result., Conclusion: Here, we describe how paired DNA-RNA MGPT can be used to solve missing heritability in FAP families, which can have important implications in family planning and treatment decisions for patients and their families.

Our aim in this study was to examine the impact of fans (vs. no fans), geographical location of league, and team ability on home winning percentage (HW%) or home advantage (HA) in professional European basketball. Data were collected from five prestigious professional, national basketball leagues within Europe (Spain, Germany, Italy, Greece and Israel) across 16 regular seasons (2005-2006 to 2020-2021). We conducted comparisons between matches with and without fans, location of leagues, team ability (High, Medium, Low), and combinations of these factors via non-parametric tests (e.g., Mann-Whitney tests, Kruskal-Wallis). We found significantly greater HA during matches with fans for leagues in Germany ( p = .001), Italy ( p = .012) and Spain ( p = .002). For matches with fans, HA and HW% were significantly different between several, but not all, leagues for high ( p < .05), medium ( p < .05) and low ( p < .02) team abilities. In conclusion, HA and HW% were enhanced by spectator attendance, with this phenomenon varying by location/region and team ability. Consideration of these multiple contextual factors may assist coaches and sport organizations to develop key strategies for enhanced team success., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Resilience has been reported to attenuate psychological burden and promote mental health. Military personnel constitute a population with a high psychological burden and poor sleep quality and are thus at a high risk of depression. This study is aim to examine the mechanism underlying the effects of resilience on perceived stress, sleep quality, and depression among Taiwanese army military personnel. A cross-sectional survey was conducted between May 2020 and February 2021. Participants comprised 1505 voluntary army military service personnel aged 20 years or older; they completed self-reported questionnaires measuring their perceived stress, resilience, sleep quality, and depression. Data were analysed using structural equation modelling. The results indicated that the association between resilience and depression was partially mediated by perceived stress and sleep quality. Perceived stress is a significant mediator on the association between resilience and depression. A high level of sleep disturbance was observed in this population and results found that sleep quality showed a slight partial mediation effect on the association between resilience and depression. Resilience can alleviate the effects of stress, which in turn alleviates depression among military personnel. Promoting resilience-enhancing education and mitigating environmental barriers to sleep is essential for reducing depressive symptoms among military personnel., (© 2023 John Wiley & Sons Ltd.)

Background: Adequate exposure to operative trauma is not uniform across surgical residencies, and therefore it can be challenging to achieve competency during residency alone. This study introduced the Cut Suit surgical simulator with an Advanced Surgical Skills Package, which replicates traumatic bleeding and organ injury, into surgery resident training across multiple New York City trauma centers., Methods: Trainees from 6 ACS-verified trauma centers participated in this prospective, observational trial. Groups of 3-5 trainees (post-graduate year 1-6) from 6 trauma centers within the largest public healthcare network in the U.S. participated. Residents were asked to perform various operative tasks including rescucitative thoracotomy, exploratory laprotomy, splenectomy, hepatorrhaphy, retroperitoneal exploration, and small bowel resection on a severely injured simulated patient. Pre- and post-course surveys were used to evaluate trainees' confidence performing these procedures and quizzes were used to evaluate participants' knowledge acquisition after the simulation., Results: One hundred twenty-three surgery residents participated in the evaluation. 68% of participants agreed that the simulation was similar to actual surgery. After the simulation, the percentage of residents reporting being "more confident" or "most confident" in independently managing operative trauma patients increased by 42% ( P < .01). There was a significant increase in the proportion of residents reporting being "more confident" or "most confident" managing all procedures performed. Post-activity quiz scores improved by an average of 20.4 points., Discussion: The Cut Suit surgical simulator with ASSP is a realistic and useful adjunct in training surgeons to manage complex operative trauma., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Catalytic methodologies that enable the synthesis of complex organic molecules from simple and readily available starting materials represent a goal in modern synthetic chemistry. In particular, multicomponent carboboration reactions that provide stereoselective access to densely functionalized building blocks are particularly valuable to achieve molecular diversity. This Perspective covers the developments in the area of catalytic allylboration of alkynes and highlights the key features that have allowed for the control of the regio-, diastereo-, and enantioselectivity in these transformations., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

There is growing evidence that supports a role of gut dysbiosis in the pathogenesis of psoriasis (Pso). Thus, probiotic supplementation and fecal microbiota transplantation may serve as promising preventive and therapeutic strategies for patients with Pso. One of the basic mechanisms through which the gut microbiota interacts with the host is through bacteria-derived metabolites, usually intermediate or end products produced by microbial metabolism. In this study, we provide an up-to-date review of the most recent literature on microbial-derived metabolites and highlight their roles in the immune system, with a special focus on Pso and one of its most common comorbidities, psoriatic arthritis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Target identification involves deconvoluting the protein target of a pharmacologically active, small-molecule ligand, a process that is critical for early drug discovery yet technically challenging. Photoaffinity labelling strategies have become the benchmark for small-molecule target deconvolution, but covalent protein capture requires the use of high-energy ultraviolet light, which can complicate downstream target identification. Thus, there is a strong demand for alternative technologies that allow for controlled activation of chemical probes to covalently label their protein target. Here we introduce an electroaffinity labelling platform that leverages the use of a small, redox-active diazetidinone functional group to enable chemoproteomic-based target identification of pharmacophores within live cell environments. The underlying discovery to enable this platform is that the diazetidinone can be electrochemically oxidized to reveal a reactive intermediate useful for covalent modification of proteins. This work demonstrates the electrochemical platform to be a functional tool for drug-target identification., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Loss of function variants in the NF1 gene cause neurofibromatosis type 1 (NF1), a genetic disorder characterized by complete penetrance, prevalence of 1 in 3,000, characteristic physical exam findings, and a substantially increased risk for malignancy. However, our understanding of the disorder is entirely based on patients ascertained through phenotype-first approaches. Leveraging a genotype-first approach in two large patient cohorts, we demonstrate unexpectedly high prevalence (1 in 450-750) of NF1 pathogenic variants. Half were identified in individuals lacking clinical features of NF1, with many appearing to have post-zygotic mosaicism for the identified variant. Incidentally discovered variants were not associated with classic NF1 features but were associated with an increased incidence of malignancy compared to a control population. Our findings suggest that NF1 pathogenic variants are substantially more common than previously thought, often characterized by somatic mosaicism and reduced penetrance, and are important contributors to cancer risk in the general population.

Aims and Objectives: To investigate the factors affecting quality of life in healthcare providers who care for patients with COVID-19., Background: Healthcare providers caring for COVID-19 patients during the pandemic suffered a deterioration in their quality of life. Several studies have explored their psychological impact of working with COVID patients, but none have examined the causes of this deterioration., Design: A cross-sectional study., Methods: In the current study, the authors investigated the factors affecting quality of life in 293 healthcare providers recruited from a medical centre in northern Taiwan who had recently cared for patients with suspected or confirmed COVID-19 by analysing their responses to an online self-report questionnaire, using bivariate correlations and structural equation modelling. Reporting of this research adheres to the STROBE guideline., Results: The study identified an important sequence of factors that mediated the effects of perceived success of epidemic prevention policies, family relations problems and education level on quality of life in a sample of healthcare workers caring for COVID-19 patients. The mediators were use of approach-oriented coping strategies and current mental health status. Specifically, use of approach-oriented coping strategies was found to directly cause improved quality of life and indirectly cause improved mental health, whereas use of avoidant coping strategies was found to directly cause worsening of mental health. Poor mental health predicted poor quality of life., Conclusions: Results suggest that implementation of sound epidemic prevention policies that promote adoption of approach-oriented coping behaviour should lead to a better quality of life in the future for healthcare providers working in challenging circumstances., Relevance to Clinical Practice: Assessment of these policies as well as the providers' family relations are necessary first steps to improving the success of approach-oriented coping behaviour in this population, which in turn can improve their mental health and quality of life., Patient or Public Contribution: Neither patients nor members of the public were involved in the design or execution of the study., (© 2023 John Wiley & Sons Ltd.)

DA1/DAR proteins play a crucial role in plant biomass production. However, their functions in woody plants in response to abiotic stress are still unknown. In this study, a total number of six PagDA1/DAR family genes were identified in the poplar genome, and the biological functions of PagDA1a and PagDA1b in the resistance to salt and drought stresses were investigated in transgenic poplar. PagDA1a and PagDA1b were ubiquitously expressed in roots, stems, and leaves, with predominant expression in roots, and were significantly induced by abiotic stress and ABA. Transgenic poplar overexpressing either PagDA1a or PagDA1b showed restrained growth but improved resistance to salt and drought stresses. Further ion content and antioxidant enzyme expression analyses exhibited that transgenic poplar accumulated less sodium (Na + ), hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) in the leaves, accompanied with increased activity of superoxide dismutase (SOD), ascorbate peroxidase (APX) and catalase (CAT), and up-regulated transcription of SOD1, APX1, and CAT2. Our observations demonstrate that PagDA1a and PagDA1b improve salt and drought tolerance through ion homeostasis optimization and ROS scavenging ability enhancement in transgenic poplar, and both can be used for the future genetic breeding of new salt and drought tolerant tree species., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Pathogenic protein-truncating variants of RAD51C, which plays an integral role in promoting DNA damage repair, increase the risk of breast and ovarian cancer. A large number of RAD51C missense variants of uncertain significance (VUS) have been identified, but the effects of the majority of these variants on RAD51C function and cancer predisposition have not been established. Here, analysis of 173 missense variants by a homology-directed repair (HDR) assay in reconstituted RAD51C-/- cells identified 30 nonfunctional (deleterious) variants, including 18 in a hotspot within the ATP-binding region. The deleterious variants conferred sensitivity to cisplatin and olaparib and disrupted formation of RAD51C/XRCC3 and RAD51B/RAD51C/RAD51D/XRCC2 complexes. Computational analysis indicated the deleterious variant effects were consistent with structural effects on ATP-binding to RAD51C. A subset of the variants displayed similar effects on RAD51C activity in reconstituted human RAD51C-depleted cancer cells. Case-control association studies of deleterious variants in women with breast and ovarian cancer and noncancer controls showed associations with moderate breast cancer risk [OR, 3.92; 95% confidence interval (95% CI), 2.18-7.59] and high ovarian cancer risk (OR, 14.8; 95% CI, 7.71-30.36), similar to protein-truncating variants. This functional data supports the clinical classification of inactivating RAD51C missense variants as pathogenic or likely pathogenic, which may improve the clinical management of variant carriers., Significance: Functional analysis of the impact of a large number of missense variants on RAD51C function provides insight into RAD51C activity and information for classification of the cancer relevance of RAD51C variants., (©2023 The Authors; Published by the American Association for Cancer Research.)

An environmentally friendly physical processing method, hydrothermal treatment (HT), was used to increase the content of specific compounds and antioxidant activities of seed-used pumpkin byproducts. The influence of hydrothermal temperature (80 °C-160 °C) and time (30-150 min) on changes in polyphenols and antioxidation was evaluated. The results revealed that the maximum free polyphenol content (140 °C for 120 min) was 3.96-fold higher than the untreated samples. Elevated temperature and long duration changed phenolic acid contents. For example, p-coumaric acid, rutin and chlorogenic acid exhibited a decreasing trend, and p-hydroxybenzoic acid, quercetin and cinnamic acid showed an increasing trend. Compared to controls, HT was significantly associated with increased antioxidant activities. To comprehensively reveal the influence of hydrothermal temperature and time on changes in polyphenolic content, back propagation artificial neural network (BP-ANN) models with accurate prediction ability were developed, and the results exhibited well-fitted and strong approximation ability (R 2  > 0.95 and RMSE < 2 %) and stability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A proportion of patients who recovered from COVID-19 have ongoing, recurrent, or new symptoms with negative nucleic acid/antigen test results, which has become a new public health problem that needs to be concerned. Traditional Chinese medicine (TCM) has shown its unique advantages in preventing, treating, and rehabilitating COVID-19. To further standardize clinician's clinical diagnosis and use of TCM for the treatment of common symptoms associated with COVID-19 infection following negative nucleic acid/antigen results, the front-line clinical experts were invited for discussion on the concepts, etiology, clinical manifestations of post-COVID-19 condition, and on treatment with TCM to form the consensus. Clinicians of TCM, Western medicine, or integration of both can use this consensus document for clinical practice and research purposes., Competing Interests: Junhua Zhang and Boli Zhang are editorial board members of this journal. None of the other authors declare any conflicts of interest., (Copyright © 2023 Tianjin University of Traditional Chinese Medicine.)

Introduction: Prior studies have shown that the surgical stabilization of rib fractures (SSRF) for patients with multiple rib fractures is associated with improved outcomes by restoring chest wall integrity and decreasing time to return to prior functional status. It is unclear if patients with pulmonary comorbidities (PCM) would benefit from this procedure., Objective: To compare the difference in morbidity and mortality of patients with multiple rib fractures undergoing SSRF who have underlying PCM to those who do not have PCM., Methods: We performed a retrospective cohort study of patients with multiple rib fractures using data from the Trauma Quality Improvement Program (January 2015 to December 2018). Patients with penetrating injuries, those who died within the first 24 h, those with substantial head, spine, or abdominopelvic injuries, and those who were pregnant, were excluded. A PCM was defined as chronic lower respiratory disease, active smoking, or morbid obesity. Dichotomous outcomes were adjusted for potential confounders by creating a propensity score for PCM and applying inverse probability weighting. The propensity score accounted for multiple patient-level and hospital level covariates. Continuous outcomes were adjusted for these same covariates using multivariable quantile regression., Results: Of the 4,084 patients who underwent SSRF, 3048 (75%) were males, the median age was 57 years [IQR 47, 66], and 1504 (37%) had at least one PCM. After adjusting for the propensity score, patients with PCM who underwent SSRF had no significant difference in mortality compared to those without PCM (absolute difference, 0.7% [95% CI -0.2, 1.7]). Similarly, there was no significant difference in time on the ventilator (0.6 days [-0.1, 1.4]). Patients with PCM, however, had a statistically significantly longer hospital LOS (0.8 days [0.3, 1.3]) and ICU LOS (0.6 days [0.1, 1.1]), higher risk of tracheostomy (2.7% [0.1, 4.6]) and higher probability of pulmonary complications (2.7% [1.2, 4.2]), compared to those without PCM., Conclusion: Among patients with multiple rib fractures who undergo SSRF, having a PCM did not result in a clinically important higher probability of dying or experiencing substantial morbidity. This factor should not exclude patients with PCM from receiving SSRF for multiple rib fractures but the small increased risk in morbidity should be discussed with patients prior to SSRF., Competing Interests: Declarations of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A novel engineered CCL20 locked dimer (CCL20LD) is nearly identical to the naturally occurring chemokine CCL20 but blocks CCR6-mediated chemotaxis and offers a new approach to treat the diseases of psoriasis and psoriatic arthritis. Methods for quantifying CCL20LD serum levels are needed to assess pharmacokinetics parameters and evaluate drug delivery, metabolism, and toxicity. Existing ELISA kits fail to discriminate between CCL20LD and the natural chemokine, CCL20WT (the wild type monomer). Herein, we tested several available CCL20 monoclonal antibodies to be able to identify one clone that can be used both as a capture and a detection antibody (with biotin-labeling) to specifically detect CCL20LD with high specificity. After validation using recombinant proteins, the CCL20LD-selective ELISA was used to analyze blood samples from CCL20LD treated mice, demonstrating the utility of this novel assay for preclinical development of a biopharmaceutical lead compound for psoriatic disease., Competing Interests: Declaration of Competing Interest STH, BFV, MBD, WFC, FCP, and CAK have financial interest in and are officers of XLock Biosciences, which produces the CCL20LD., (Copyright © 2023. Published by Elsevier B.V.)

To quantify and compare the external peak demands (PD) encountered according to game result (win vs. loss), quarter result (win vs. tie vs. loss), and quarter point difference (± difference in score) in under-18 years (U18), male basketball players. Thirteen basketball players had external load variables monitored across 9 games using local positioning system technology, including distance covered, distance covered in different intensity zones, accelerations, decelerations, and PlayerLoad™. PD were calculated across 30-s, 1-min, and 5-min time windows for each variable. Linear mixed models were used to compare PD for each variable according to game result (win vs. loss), quarter result (win vs tie vs loss), and quarter point difference (high vs. low). External PD were comparable between games that were won and lost for all variables and between quarters that were won and lost for most variables (p > 0.05, trivial-small effects). In contrast, players produced higher (p < 0.05, small effects) 1-min high-speed running distance and 5-min PlayerLoad TM in quarters that were won compared to quarters that were lost. Additionally, high quarter point differences (7.51 ± 3.75 points) elicited greater (p < 0.05, small effects) external PD (30-s PlayerLoad TM , 30-s and 5-min decelerations, and 1-min and 5-min high-speed running distance) than low quarter point differences (-2.47 ± 2.67 points). External PD remain consistent (trivial-small effects) regardless of game result, quarter result, and quarter point difference in U18, male basketball players. Accordingly, external PD attained during games may not be a key indicator of team success., (Copyright © Biology of Sport 2023.)

The production of glycyrrhetinic acid (GA) and 11-oxo-β-amyrin, the major bioactive components in liquorice, was typically inhibited by P450 oxidation in Saccharomyces cerevisiae . This study focused on optimizing CYP88D6 oxidation by balancing its expression with cytochrome P450 oxidoreductase (CPR) for the efficient production of 11-oxo-β-amyrin in yeast. Results indicated that a high CPR:CYP88D6 expression ratio could decrease both 11-oxo-β-amyrin concentration and turnover ratio of β-amyrin to 11-oxo-β-amyrin, whereas a high CYP88D6:CPR expression ratio is beneficial for improving the catalytic activity of CYP88D6 and 11-oxo-β-amyrin production. Under such a scenario, 91.2% of β-amyrin was converted into 11-oxo-β-amyrin in the resulting S. cerevisiae Y321, and 11-oxo-β-amyrin production was further improved to 810.6 mg/L in fed-batch fermentation. Our study provides new insights into the expression of cytochrome P450 and CPR in maximizing the catalytic activity of P450s, which could guide the construction of cell factories in producing natural products.

Purpose: To manage intra-fractional motions, recent developments in tomotherapy enable a unique capability of adjusting MLC/jaw to track the moving target based on the intra-fractional motions detected by sequential monoscopic imaging. In this study, we evaluated the effectiveness of motion compensation with a realistic imaging rate for prostate stereotactic body radiotherapy (SBRT). The obtained results will guide optimizing treatment parameters and image-guided radiation therapy (IGRT) in tomotherapy using this approach., Methods: Ten retrospective prostate cases with actual prostate motion curves previously recorded through the Calypso system were used in this study. Based on the recorded peak-to-peak motion, these cases represented either large (> 5 mm) or median (≤ 5 mm) intra-fractional prostate motions. All the cases were re-planned on tomotherapy using 35 Gy/5 fractions SBRT regimen and three different jaw settings of 1 cm static, 2.5 cm static, and 2.5 cm dynamic jaw. Two motion compensation methods were evaluated: a complete compensation that adjusted the jaw and MLC every 0.1 s (the same rate as the Calypso motion trace), and a realistic compensation that adjusted the jaw and MLC at an average imaging interval of 6 s from sequential monoscopic images. An in-house 4D dose calculation software was then applied to calculate the dosimetric outcomes from the original motion-free plan, the motion-contaminated plan, and the two abovementioned motion-compensated plans. During the process, various imaging rates were also simulated in one case with unusually large motions to quantify the impact of the KV-imaging rate on the effectiveness of motion compensation., Results: The effectiveness of motion compensation was evaluated based on the PTV coverage and OAR sparing. Without any motion-compensation, the PTV coverage (PTV V100%) of patients with large prostate motions decreased remarkably to 55%-82% when planning with the 1 cm jaw but to a less level of 67-94% with the 2.5 cm jaw. In contrast, motion compensation improved the PTV coverage (>92%) when combined with the 2.5 cm jaw, but less effective, around 75%-94%, with the 1 cm jaw. For OAR sparing, the bladder D1cc, bladder D10cc, and rectum D1cc all increased in the motion-contaminated plans. Motion compensation improved OAR sparing to the equivalent level of the original motion-free plans. For patients with median prostate motion, motion-induced degradation in PTV coverage was only observed when planning with the 1 cm jaw. After motion compensation, the PTV coverage improved to better than 94% for all three jaw settings. Additionally, the effectiveness of motion compensation depends on the imaging rate. Motion compensation with a typical rate of two KV images per gantry rotation effectively reduces motion-induced dosimetric uncertainties. However, a higher imaging rate is recommended when planning with a 1 cm jaw for patients with large motions., Conclusion: Our results demonstrated that the performance of sequential monoscopic imaging-guided motion compensation on tomotherapy depends on the amplitude of intra-fractional prostate motion, the plan parameter settings, especially jaw setting, gantry rotation, and the imaging rate for motion compensation. Creating a patient-specific imaging guidance protocol is essential to balance the effectiveness of motion compensation and achievable imaging rate for intra-fractional motion tracking., (© 2022 American Association of Physicists in Medicine.)

A promising drying technology, namely combined freeze-drying and far-infrared drying (FD-FIRD) was employed to dehydrate seed-used pumpkin (SUP) and its effects on physical characteristics (color, microstructure, texture, shrinkage), bioactive components (phenolics and carotenoids) of SUP were evaluated. The low-field nuclear magnetic resonance (LF-NMR) was used to analyze moisture state and distribution during FD process, which is beneficial for choosing appropriate moisture transfer point. Results showed that most free water (87.29 %) was removed when drying time reached 25 h, thus retaining original tissue structure of sample with almost no deformation during later FIRD process. Therefore, FD for 25 h followed by FIRD for 2 h (FD25-FIRD2) sample exhibited similar appearance with FD sample. The free phenolics content of FD-FIRD samples was 14.97 %-26.60 % higher than that of FD depending on FIRD duration. Especially, p-coumaric acid content of FD25-FIRD2 sample increased of 32.23 %. Besides, FD-FIRD performed higher retention for carotenoids showing 3.00-3.39 folds than FIRD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: The diagnosis of pulmonary infection and the identification of pathogens are still clinical challenges in immunocompromised patients. Metagenomic next-generation sequencing (mNGS) has emerged as a promising infection diagnostic technique. However, its diagnostic value in immunocompromised patients needs further exploration., Purposes: This study was to evaluate the diagnostic value of mNGS compared with comprehensive conventional pathogen tests (CTs) in the etiology of pneumonia in immunocompromised patients and immunocompetent patients., Methods: We retrospectively reviewed 53 patients who were diagnosed with pneumonia from May 2019 to June 2021. There were 32 immunocompromised patients and 21 immunocompetent patients with pneumonia who received both mNGS and CTs. The diagnostic performance was compared between mNGS and CTs in immunocompromised patients, using the composite diagnosis as the reference standard. And, the diagnostic value of mNGS for mixed infections was further analyzed., Results: Compared to immunocompetent patients, the most commonly pathogens, followed by Cytomegalovirus , Pneumocystis jirovecii and Klebsiella pneumoniae in immunocompromised patients. Furthermore, more mixed infections were diagnosed, and bacterial-fungal-virus coinfection was the most frequent combination (43.8%). mNGS can detect more types of pathogenic microorganisms than CTs in both groups (78.1% vs. 62.5%, P = 0.016and 57.1% vs. 42.9%, P = 0.048). The overall diagnostic positive rate of mNGS for pathogens was higher in immunocompromised patients ( P = 0.002). In immunocompromised patients, a comparable diagnostic accuracy of mNGS and CTs was found for bacterial, fungal, and viral infections and coinfection. mNGS had a much higher sensitivity for bacterial infections (92.9% vs. 50%, P < 0.001) and coinfections (68.8% vs. 48.3%, P < 0.05), and it had no significant advantage in the detection of fungal infections, mainly due to the high sensitivity for Pneumocystis jirovecii in both groups., Conclusion: mNGS is more valuable in immunocompromised patients and exhibits apparent advantages in detecting bacterial and mixed infections. It may be an alternative or complementary diagnostic method for the diagnosis of complicated infections in immunocompromised patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jun Li et al.)

Competing Interests: We have no competing interests to declare.

Functionalized alicyclic amines are important building blocks for the synthesis of bioactive natural compounds and drugs. Existing methods of functionalization are typically limited to the synthesis of protected amines or the use of highly basic organometallic reagents that can compromise functional group tolerance. Here, we report a novel approach that enables the transformation of O -benzoyl hydroxylamines into α-functionalized cyclic secondary amines by means of a copper-catalyzed regio-, stereo-, and chemoselective coupling with allenes and bis(pinacolato)diboron. A key feature of the present transformation is the use of a catalytic Lewis base additive which inhibits the competing C-N bond forming reaction between the catalytically generated boron-substituted allylcopper intermediate with the O -benzoyl hydroxylamine, thus enabling in situ transformation of the latter into an alicyclic imine which undergoes selective C-C bond formation with the allylcopper species.

Background: During early spring 2020, New York City (NYC) rapidly became the first US epicenter of the COVID-19 pandemic. With an unparalleled strain on health care resources, we sought to investigate the impact of the pandemic on trauma visits and mortality in the United States' largest municipal hospital system., Methods: We conducted a retrospective multicenter cohort study of the five level 1 trauma centers in NYC's public health care system, New York City's Health and Hospitals Corporation. Clinical characteristics, mechanism of injury, and mortality of trauma patients presenting during the early pandemic (March 1, 2020, to May 31, 2020) were compared with a similar period in the previous 2 years. To account for important patient and hospital-level confounding variables, we created a propensity score for treatment and applied inverse probability weighting., Results: In March to May 2020, there was a 25% decrease in median number of monthly trauma visits (693 vs. 528; p = 0.02) but a 50% increase (15% vs. 22%; p = <0.001) in patients presenting for penetrating injuries, compared with the same period for 2018 and 2019. Injured patients with COVID were significantly more likely to die compared with those without COVID-19 (10.5% vs. 3.6%; p < 0.001). Overall, there was no significant difference in mortality for non-COVID-injured New Yorkers cared for in 2020 compared with 2018 and 2019. Less severely injured non-COVID patients (Injury Severity Score, <15), however, were significantly more likely to die compared with this same subgroup in 2018 and 2019 (adjusted relative risk, 2.7 [95% confidence interval, 1.5-4.7])., Conclusion: Despite a decline in overall trauma visits during the early part of the COVID pandemic in NYC, there was a significant increase in the proportion of penetrating mechanisms. Less-injured non-COVID patients experienced an increase in mortality in the early pandemic, possibly from a depletion of human and hospital resources from the large influx of COVID patients. These data lend support to the safeguarding of trauma system resources in the event of a future pandemic., Level of Evidence: Prognostic and Epidemiologic; Level III., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Effects of blanching (BL), ultrasound (US) and freeze-thawing (FT) pretreatments prior to far-infrared drying (FIRD) on drying characteristics, water distribution, and quality parameters of seed-used pumpkin (SUP) slices were investigated in this study. US, BL and FT pretreatments significantly accelerated drying rate due to the destruction of cell structure. Modified Page model was the fittest model for predicting the FIRD process. Low field nuclear magnetic resonance (LF-NMR) results revealed that T 2 distribution curves of all pretreated samples moved rapidly to the positive x-axis direction, indicating an increase in the rate of water migration. The color of US-FIRD was closer to fresh SUP. BL-FIRD exhibited the highest free polyphenols content (241.28 ± 1.11 mg GAE/100 g DW) and total carotenoids content (129.69 ± 2.49 μg/ g DW), increasing by 45% and 34% respectively compared to the untreated sample., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Loss-of-function variants in the BRCA1 and BRCA2 susceptibility genes predispose carriers to breast and/or ovarian cancer. The use of germline testing panels containing these genes has grown dramatically, but the interpretation of the results has been complicated by the identification of many sequence variants of undefined cancer relevance, termed "Variants of Uncertain Significance (VUS)." We have developed functional assays and a statistical model called VarCall for classifying BRCA1 and BRCA2 VUS. Here we describe a multifactorial extension of VarCall, called VarCall XT, that allows for co-analysis of multiple forms of genetic evidence. We evaluated the accuracy of models defined by the combinations of functional, in silico protein predictors, and family data for VUS classification. VarCall XT classified variants of known pathogenicity status with high sensitivity and specificity, with the functional assays contributing the greatest predictive power. This approach could be used to identify more patients that would benefit from personalized cancer risk assessment and management., (© 2022. The Author(s).)

Background: Despite mostly favorable past evidence for use of intracranial pressure monitoring (ICPM), more recent data question not only the indications but also the utility of ICPM. The Fourth Edition Brain Trauma Foundation guidelines offer limited indications for ICPM. Evidence supports ICPM for reducing mortality in patients with severe traumatic brain injury (TBI) and cites decreased survival in elderly patients., Methods: All patients ≥ 18 years of age with isolated TBI, head Abbreviated Injury Scale (AIS) ≥ 3, and a Glasgow Coma Scale (GCS) ≤ 8 between 2008 and 2014 were included from the National Trauma Data Bank. Exclusion criteria were head AIS = 6 and death within 24 hours. Patients with and without ICPM were compared using TBI-specific variables. Patients were then matched via propensity-score matching (PSM), and the odds ratio (OR) of death with ICPM was determined using logistic regression modeling for 8 different age strata., Results: A total of 23,652 patients with a mean age of 56 years, median head AIS of 4, median GCS of 3, and overall mortality of 29.2% were analyzed. After PSM, ICPM was associated with death beginning at the age stratum of 56-65 years. Intracranial pressure monitoring was associated with survival beginning at the age-group 36-45 years., Discussion: Based on a large propensity-matched sample of TBI patients, ICPM was not associated with improved survival for TBI patients above 55 years of age. Until level 1 evidence is available, this age threshold should be considered for further prospective study in determining indications for ICPM.

Weight change from childhood to adolescence has been understudied in Asian Americans. Known studies lack disaggregation by Asian subgroups. This retrospective study assessed the weight status change in 1500 Chinese American children aged 5−11 years from an urban primary care health center between 2007 and 2017. Weight status was categorized using the 2000 CDC growth charts into “underweight/normal weight” and “overweight/obese.” The overweight/obesity prevalence in 2007 and 2017 were determined. McNemar’s test and logistic regression were performed. The prevalence of overweight/obesity decreased from 29.9% in 2007 to 18.6% in 2017. Children who were overweight/obese at 5−11 years had 10.3 increased odds of staying overweight/obese over time (95% CI = 7.6−14.0, p < 0.001) compared to their underweight/normal weight counterparts. Of the children who were overweight/obese in 2007, 45.7% remained overweight/obese ten years later. Childhood overweight/obesity strongly predicts adult overweight/obesity in Chinese Americans. Targeted education and intervention are warranted to prevent adult obesity.

The purpose of this study was to compare external peak demands (PDs) across quarters (Q) in basketball. Thirteen elite, junior, male basketball players were monitored using electronic performance tracking systems. There were studied intervals for different time windows to determine the external PD for distance (m); player load; distance covered in four different zones; accelerations; and decelerations. A mixed linear model was run to identify differences among quarters, and the auto-correlation function was carried out to determine fluctuations across the whole game. The results showed significant differences between Q1 vs. Q2 for distance, player load, and standing-walking distance; between Q1 vs. Q3 for distance, player load, and HSR; between Q1 vs. Q4 for distance, player load, standing-walking, and HSR; and between Q3 vs. Q4 for distance and player load. These findings suggest that external PD for running-based demands (distance, player load, and high-speed running) decrease across basketball games with the most notable declines occurring between the first and fourth quarters. Nevertheless, it is important to note that non-significant differences were found between quarters for several external PD variables (jogging, running, acceleration, and deceleration) across different time windows. Findings from the present study reinforce the importance of considering specific PD variables for different functions due to the specific insight each provides., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alonso Pérez-Chao, Gómez, Lisboa, Trapero, Jiménez and Lorenzo.)

Von Hippel-Lindau disease (VHL) is an autosomal dominant, inherited syndrome with variants in the VHL gene causing predisposition to multi-organ benign and malignant neoplasms. A germline VHL variant is identified in 95-100% of individuals with a clinical diagnosis of VHL. Here, we present the case of an individual with a clinical diagnosis of VHL disease where peripheral blood DNA analysis did not detect a VHL variant. Sequencing of four tumor tissues (ccRCC, pheochromocytoma, lung via sputum, liver) revealed a VHL c.593 T > C (p.Leu198Pro) variant at varying allele fractions (range: 10-55%) in all tissues. Re-examination of the peripheral blood sequencing data identified this variant at 6% allele fraction. Tumor analysis revealed characteristic cytomorphological, immunohistochemical reactivity for alpha-inhibin, and CAIX, and reduced pVHL reactivity supported VHL-related pseudohypoxia. This report of a rare case of VHL mosaicism highlights the value of tissue testing in VHL variant negative cases., (© 2022. The Author(s).)

The effects of far-infrared radiation drying (FIRD), freeze drying (FD), vacuum drying (VD), and hot air drying (HAD) on appearance, physicochemical properties, antioxidant activities, antityrosinase capacity using B16F10 melanoma cell from seed-used pumpkins (hull-less pumpkin and hull pumpkin) were evaluated. Results suggested that hull-less pumpkin (HLP) dehydrated by FIRD provided the highest total polyphenols content (37.11 ± 1.05 mg GAE/ g DW) and the ability of scavenging free radicals. HPLC analysis exhibited that coumaric acid was predominant phenolic acid in pumpkin. The correlation analysis demonstrated that polyphenolic compounds were related to antioxidant capacity. HLP-FD possessed better colour, higher preservation of β-carotene, ascorbic acid and higher sugar contents compared with HLP-HAD. The highest antityrosinase activity was recorded in HLP-VD with a concentration of 37.16%. The melanin inhibition increased to 76.61%, and intracellular tyrosinase activity in B16F10 melanoma cells decreased to 88.63% at 800 μg/mL of polyphenol extract., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

MUTYH -associated polyposis (MAP) is an autosomal recessive disorder characterized by the development of multiple adenomatous colonic polyps and an increased lifetime risk of colorectal cancer. Germline biallelic pathogenic variants in MUTYH are responsible for MAP. The MUTYH c.934-2A > G (NM&#95;001128425.1) variant, which is also known as c.850-2A > G for NM&#95;001048174.2, has been identified in our laboratory in more than 800 patients, including homozygous and compound heterozygote carriers. The variant was initially classified as a variant of uncertain significance (VUS) because of lack of a MAP phenotype in biallelic carriers. In two unrelated female patients who were heterozygous carriers of this variant, further testing by RNA sequencing identified an aberrant transcript with a deletion of 9 nt at the start of exon 11 ( MUTYH r.934&#95;942del9). This event is predicted to lead to an in-frame loss of three amino acids in a noncritical domain of the protein. This was the only splice defect identified in these patients that was not present in the controls, and the aberrant transcript is derived exclusively from the variant allele, strongly supporting the cause of this splice defect as being the intronic variant, MUTYH c.934-2A > G. The splicing analysis demonstrating a small in-frame skipping of three amino acids in a noncritical domain, along with the absence of a MAP phenotype in our internal cohort of biallelic carriers, provides evidence that the variant is likely benign and not of clinical significance., (© 2022 Hernandez et al.; Published by Cold Spring Harbor Laboratory Press.)

Purpose: To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast., Materials and Methods: The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes ( ATM , BARD1 , BRCA1 , BRCA2 , BRIP1 , CDH1 , CHEK2 , PALB2 , PTEN , RAD51C , RAD51D , and TP53 ) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC)., Results: The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, CDH1 and BRCA2 PVs were associated with high risks of ILC (odds ratio [OR] > 4) and CHEK2 , ATM , and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, CDH1 PVs were > 10-fold enriched, whereas PVs in BRCA1 were substantially reduced in ILC., Conclusion: The study establishes that PVs in ATM , BRCA2 , CDH1 , CHEK2 , and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but CDH1 should be specifically discussed because of low prevalence and gastric cancer risk., Competing Interests: Jeffrey N. WeitzelSpeakers' Bureau: AstraZeneca Celine M. VachonStock and Other Ownership Interests: Exact Sciences (I)Research Funding: GRAILPatents, Royalties, Other Intellectual Property: Breast Density softwareTravel, Accommodations, Expenses: GRAIL Allison W. KurianResearch Funding: Myriad GeneticsOther Relationship: Ambry Genetics, Color Genomics, GeneDx/BioReference, InVitae, Genentech Rachid KaramEmployment: Ambry GeneticsResearch Funding: Ambry GeneticsTravel, Accommodations, Expenses: Ambry Genetics Elizabeth ChaoEmployment: Ambry Genetics Amal YussufEmployment: Ambry Genetics Tina PesaranEmployment: Ambry Genetics/Konica Minolta Jill S. DolinskyEmployment: Ambry Genetics Holly LaDucaEmployment: Ambry GeneticsStock and Other Ownership Interests: Ambry Genetics Eric C. PolleyResearch Funding: GRAIL Susan M. DomchekHonoraria: AstraZeneca, Clovis Oncology, Bristol Myers SquibbResearch Funding: AstraZeneca, Clovis Oncology Fergus J. CouchConsulting or Advisory Role: AstraZenecaSpeakers' Bureau: Ambry Genetics, QiagenResearch Funding: GRAILTravel, Accommodations, Expenses: GRAIL, QiagenOther Relationship: Ambry GeneticsNo other potential conflicts of interest were reported.

Traumatic brain injury (TBI) can lead to severe adverse clinical outcomes, including death and disability. Early detection of in-hospital mortality in high-risk populations may enable early treatment and potentially reduce mortality using machine learning. However, there is limited information on in-hospital mortality prediction models for TBI patients admitted to emergency departments. The aim of this study was to create a model that successfully predicts, from clinical measures and demographics, in-hospital mortality in a sample of TBI patients admitted to the emergency department. Of the 4881 TBI patients who were screened at the emergency department at a high-level first aid duty hospital in northern Taiwan, 3331 were assigned in triage to Level I or Level II using the Taiwan Triage and Acuity Scale from January 2008 to June 2018. The most significant predictors of in-hospital mortality in TBI patients were the scores on the Glasgow coma scale, the injury severity scale, and systolic blood pressure in the emergency department admission. This study demonstrated the effective cutoff values for clinical measures when using machine learning to predict in-hospital mortality of patients with TBI. The prediction model has the potential to further accelerate the development of innovative care-delivery protocols for high-risk patients.

Purpose: The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have < 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years., Methods: A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs., Results: The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in BRCA1 , BRCA2 , and PALB2 were found in 3.42% of women diagnosed with estrogen receptor (ER)-negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in CHEK2 , PALB2 , BRCA2 , and BRCA1 were associated with increased risks (odds ratio = 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were ≥ 15% for those with PVs in BRCA1 , BRCA2 , and PALB2 ., Conclusion: This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with BRCA1 and BRCA2 PVs and perhaps with PALB2 and CHEK2 PVs should be considered for magnetic resonance imaging screening., Competing Interests: Jeffrey N. WeitzelSpeakers' Bureau: AstraZeneca Amal YussufEmployment: Ambry Genetics Celine M. VachonStock and Other Ownership Interests: Exact SciencesResearch Funding: GRAILPatents, Royalties, Other Intellectual Property: Breast Density softwareTravel, Accommodations, Expenses: GRAIL Tina PesaranEmployment: Ambry Genetics/Konica MinoltaTravel, Accommodations, Expenses: Ambry Genetics/Konica Minolta Irene M. OngEmployment: Propeller HealthStock and Other Ownership Interests: AyrFlo Rachid KaramEmployment: Ambry GeneticsResearch Funding: Ambry GeneticsTravel, Accommodations, Expenses: Ambry Genetics Holly LaDucaEmployment: Ambry GeneticsStock and Other Ownership Interests: Ambry Genetics Jill S. DolinskyEmployment: Ambry Genetics Elizabeth ChaoEmployment: Ambry Genetics Eric C. PolleyResearch Funding: GRAIL Susan M. DomchekHonoraria: AstraZeneca, Clovis Oncology, Bristol Myers SquibbResearch Funding: AstraZeneca, Clovis OncologyOpen Payments Link: https://openpaymentsdata.cms.gov/physician/917904 Fergus J. CouchConsulting or Advisory Role: AstraZenecaSpeakers' Bureau: Ambry Genetics, QiagenResearch Funding: GRAILTravel, Accommodations, Expenses: GRAIL, QiagenOther Relationship: Ambry GeneticsNo other potential conflicts of interest were reported.