PowerNovo: de novo peptide sequencing via tandem mass spectrometry using an ensemble of transformer and BERT models.

The primary objective of analyzing the data obtained in a mass spectrometry-based proteomic experiment is peptide and protein identification, or correct assignment of the tandem mass spectrum to one amino acid sequence. Comparison of empirical fragment spectra with the theoretical predicted one or matching with the collected spectra library are commonly accepted strategies of proteins identification and defining of their amino acid sequences. Although these approaches are widely used and are appreciably efficient for the well-characterized model organisms or measured proteins, they cannot detect novel peptide sequences that have not been previously annotated or are rare. This study presents PowerNovo tool for de novo sequencing of proteins using tandem mass spectra acquired in a variety of types of mass analyzers and different fragmentation techniques. PowerNovo involves an ensemble of models for peptide sequencing: model for detecting regularities in tandem mass spectra, precursors, and fragment ions and a natural language processing model, which has a function of peptide sequence quality assessment and helps with reconstruction of noisy sequences. The results of testing showed that the performance of PowerNovo is comparable and even better than widely utilized PointNovo, DeepNovo, Casanovo, and Novor packages. Also, PowerNovo provides complete cycle of processing (pipeline) of mass spectrometry data and, along with predicting the peptide sequence, involves the peptide assembly and protein inference blocks.

Impact of efavirenz on hormone-positive breast cancer survival in women living with HIV.

Women living with HIV and breast cancer have poorer survival than HIV-negative women. Efavirenz-estrogen interactions are documented; however, the survival impact is unknown. Survival between women with estrogen-receptor positive breast cancer taking efavirenz (n = 38) and nonefavirenz regimens (n = 51) were compared. The 5-year overall-survival was 48.9% [95% confidence interval (CI) 33.0-72.2 and 51.1% (95% CI 34.0-76.8)] in the efavirenz and nonefavirenz groups, respectively suggesting efavirenz is unlikely driving poorer survival in women living with HIV and estrogen-receptor positive breast cancer.

Typology of employers offering line manager training for mental health.

BACKGROUND: Mental ill health has a high economic impact on society and employers. National and international policy advocates line manager (LM) training in mental health as a key intervention, but little is known about employer training provisions. AIMS: To explore the prevalence and characteristics of organizations that offer LM training in mental health. METHODS: Secondary analysis of existing longitudinal anonymised organizational-level survey data derived from computer-assisted telephone interview surveys collected in four waves (2020:1900 firms, 2021:1551, 2022:1904, 2023:1902) in England, before, during and after a global pandemic. RESULTS: The proportion of organizations offering LM training in mental health increased pre- to post-pandemic (2020:50%, 2023:59%) but 41% do not currently provide it. Logistic regression confirmed that LM training is more likely to be offered by large-sized enterprises, organizations with a larger proportion of employees who are younger (aged 25-49), female, disabled and from ethnic minority communities. Sector patterns were inconsistent, but in 2023, organizations from the 'Hospitality' and 'Business Services' sectors were more likely to provide LM training than other sectors. CONCLUSIONS: Continued efforts are needed to increase the proportion of employers offering LM training in mental health, particularly small- to medium-sized enterprises, and organizations with predominantly male, White and/or older workforces.

How Do Molecular Tweezers Bind to Proteins? Lessons from X-ray Crystallography.

To understand the biological relevance and mode of action of artificial protein ligands, crystal structures with their protein targets are essential. Here, we describe and investigate all known crystal structures that contain a so-called "molecular tweezer" or one of its derivatives with an attached natural ligand on the respective target protein. The aromatic ring system of these compounds is able to include lysine and arginine side chains, supported by one or two phosphate groups that are attached to the half-moon-shaped molecule. Due to their marked preference for basic amino acids and the fully reversible binding mode, molecular tweezers are able to counteract pathologic protein aggregation and are currently being developed as disease-modifying therapies against neurodegenerative diseases such as Alzheimer's and Parkinson's disease. We analyzed the corresponding crystal structures with 14-3-3 proteins in complex with mono- and diphosphate tweezers. Furthermore, we solved crystal structures of two different tweezer variants in complex with the enzyme Δ1-Pyrroline-5-carboxyl-dehydrogenase (P5CDH) and found that the tweezers are bound to a lysine and methionine side chain, respectively. The different binding modes and their implications for affinity and specificity are discussed, as well as the general problems in crystallizing protein complexes with artificial ligands.

Group peer mentoring is effective for different demographic groups of biomedical research faculty: A controlled trial.

INTRODUCTION: Improved mentoring of midcareer researchers in medical schools has been identified as an important potential avenue for addressing low vitality and high burnout rates in faculty, and the scarcity of both underrepresented minority (URM) faculty and women in biomedical research. To address the need for widescale effective mentoring, we sought to determine whether a group peer mentoring intervention (C-Change Mentoring and Leadership Institute) for early midcareer research faculty was effective for different demographic groups in a controlled trial. METHODS AND MATERIALS: Thirty-five diverse early midcareer faculty and 70 propensity-matched (PM) control subjects matched to intervention subjects on a) study inclusion criteria; b) gender, race, and ethnicity, degree, rank, years of experience, publications, grants; and c) pretest survey outcome variables, participated in the intervention. The C-Change Participant Survey assessed vitality, self-efficacy in career advancement, research success, mentoring others, valuing diversity, cognitive empathy, and anti-sexism/anti-racism skills at pretest and intervention completion. Analysis using multiple regression models included outcome pretest values and indicator variables for intervention, gender, URM status, and MD vs. PhD. Hypotheses regarding differential effectiveness of the intervention by demographic group were tested by including cross-product terms between the demographic indicator variables and the intervention indicator. Missing data were addressed using chained equations to create 100 data sets. RESULTS AND DISCUSSION: The intervention participants had significantly higher (favorable) scores than PM controls for: self-assessed change in vitality; self-efficacy for career advancement, research, and mentoring others; cognitive empathy; and anti-sexism/racism skills. The benefits of the intervention were nearly identical across: gender, URM vs non-URM faculty, and degree MD/PhD, except vitality significantly increased for non-URM subjects, and not for URM faculty. Self-assessed change in vitality increased for URM and non-URM. CONCLUSION: The intervention worked successfully for enhancing vitality, self-efficacy and cross-cultural engagement across different demographic groups of biomedical research faculty.

Metabolomic and Proteomic Profiling of Athletes Performing Physical Activity under Hypoxic Conditions.

Proteomic and metabolomic research enables quantitation of the molecular profile of athletes. Multiomic profiling was conducted using plasma samples collected from 18 male athletes performing aerobic activity (running) at high altitude. Metabolomic profiling detected changes in the levels of 4-hydroxyproline, methionine, oxaloacetate, and tyrosine during the recovery period. Furthermore, proteomic profiling revealed changes in expression of proteins contributing to the function of the immune system, muscle damage, metabolic fitness and performance, as well as hemostasis. Further research should focus on developing metabolic models to monitor training intensity and athlete adaptation.

Discovery and Preclinical Pharmacology of NX-2127, an Orally Bioavailable Degrader of Bruton's Tyrosine Kinase with Immunomodulatory Activity for the Treatment of Patients with B Cell Malignancies.

Bruton's tyrosine kinase (BTK), a member of the TEC family of kinases, is an essential effector of B-cell receptor (BCR) signaling. Chronic activation of BTK-mediated BCR signaling is a hallmark of many hematological malignancies, which makes it an attractive therapeutic target. Pharmacological inhibition of BTK enzymatic function is now a well-proven strategy for the treatment of patients with these malignancies. We report the discovery and characterization of NX-2127, a BTK degrader with concomitant immunomodulatory activity. By design, NX-2127 mediates the degradation of transcription factors IKZF1 and IKZF3 through molecular glue interactions with the cereblon E3 ubiquitin ligase complex. NX-2127 degrades common BTK resistance mutants, including BTKC481S. NX-2127 is orally bioavailable, exhibits in vivo degradation across species, and demonstrates efficacy in preclinical oncology models. NX-2127 has advanced into first-in-human clinical trials and achieves deep and sustained degradation of BTK following daily oral dosing at 100 mg.

Trends in Obstetrics and Gynecology Residency Applications in the Year After Abortion Access Changes.

Importance: State-specific abortion restrictions currently affect the training of approximately 44% of obstetrics and gynecology (OBGYN) residents in the US. Examination of where future trainees apply for residency is important. Objective: To assess changes in the percentage of applicants to OBGYN residency programs by state based on abortion restrictions in place after the Dobbs v Jackson Women's Health Organization (hereafter, Dobbs v Jackson) US Supreme Court decision and examine whether applicants' preference for programs, as suggested by the distribution of application signals that express higher interest, was associated with abortion bans. Design, Setting, and Participants: This serial cross-sectional study used anonymized data for all applicants to OBGYN residency programs in the US during September and October from 2019 to 2023. Data were obtained from the Association of American Medical Colleges Electronic Residency Application Service. Exposures: Applications and program preference signals sent to OBGYN residency programs, analyzed by applicants' self-reported demographics. Main Outcomes and Measures: The primary outcome was differences in the percentage of unique applicants to OBGYN residency programs from 2019 to 2023, with programs categorized by state-based abortion restrictions after the Dobbs v Jackson decision. Secondary outcomes included the distribution of program signals by state abortion ban status. Results: A total of 2463 applicants (2104 [85.4%] women) who applied to OBGYN programs for the 2023 residency match cycle were the focal sample of this study. While overall applicant numbers remained stable between 2019 and 2023, the number of applicants differed significantly by state abortion ban status in the 2022 (F2,1087 = 10.82; P < .001) and the 2023 (F2,1087 = 14.31; P < .001) match cycles. There were no differences in the number of signals received by programs in states with bans after controlling for known covariates such as number of applications received and program size, and there were no differences in the percentage of signals sent by out-of-state applicants to programs in states with different abortion laws than their home states (F2,268 = 2.41; P = .09). Conclusions and Relevance: In this cross-sectional study, there was a small but statistically significant decrease in the number of applicants to OBGYN residency programs in states with abortion bans in 2023 compared with 2022. However, applicant signaling data did not vary by states' abortion ban status. While OBGYN residency programs almost completely filled in 2023, continued monitoring for the potential consequences of state abortion bans for OBGYN training is needed.

Perceived social support moderates the relations between mental health symptoms and current suicidal ideation.

Despite efforts to identify risk factors associated with suicidal ideation (SI), less work has been conducted to highlight protective factors to promote prevention. Perceived social support has been shown to positively impact a wide range of psychological outcomes; however, prior efforts exploring whether perceived social support moderates the relationship between mental health (MH) symptoms and current SI among men and women have been hampered by limitations. To address knowledge gaps, data from the Comparative Health Assessment Interview Research Study was used to evaluate whether (a) perceived social support moderates the relationship between mental health symptoms (posttraumatic stress, anxiety, alcohol use, depressive) and current SI among veterans and nonveterans; (b) the strength of this moderating effect varies by gender and veteran status; and (c) the strength of this moderating effect varies by social support source (significant other, friend, family). Results suggest that perceived social support is more protective against SI for those with lower levels of mental health symptoms (≤ 25th percentile) than for those with higher symptom levels (≥ 75th percentile). Findings were largely consistent across study groups, support sources, and mental health symptoms examined; however, a significant moderating effect on the alcohol use-SI relationship was only observed for veteran men. Those with a lower mental health symptom severity may receive more benefit from strategies aimed at increasing perceived social support compared to those with higher symptom severity. Research is needed to match protective factors to individual phenotypes, with the goal of engaging those living with SI in more effective interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

How much magnesium sulfate is needed to "keep total serum magnesium above 2.0 mg/dL"?

For patients at increased risk of life-threating ventricular arrythmias, hospitalists often administer intravenous magnesium sulfate to maintain total serum magnesium concentration (TsMg) above 2 mg/dL. How long each dose keeps TsMg above this threshold is not well known, however. We collected TsMg values from 12,618 veterans who were given 24,363 doses of intravenous magnesium sulfate during 14,901 hospitalizations for acute heart failure. Across dose amounts, the average TsMg dropped below 2.0 mg/dL within 24 h of administration. When we limited our analysis to 2 g doses (the most common dose) and adjusted for baseline TsMg, estimated glomerular filtration rate, oral magnesium supplementation, and loop diuretic dosing, we found that less than half of the adjusted TsMg values remained above 2.0 mg/dL just 12 h after dose administration. Hospitalists should expect, on average, to administer 2 g intravenous magnesium sulfate at least twice daily to maintain total serum magnesium above 2 mg/dL.

Variation observed in consensus judgments between pairs of reviewers when assessing the risk of bias due to missing evidence in a sample of published meta-analyses of nutrition research.

OBJECTIVES: To evaluate the risk of bias due to missing evidence in a sample of published meta-analyses of nutrition research using the Risk Of Bias due to Missing Evidence (ROB-ME) tool and determine inter-rater agreement in assessments. STUDY DESIGN AND SETTING: We assembled a random sample of 42 meta-analyses of nutrition research. Eight assessors were randomly assigned to one of four pairs. Each pair assessed 21 randomly assigned meta-analyses, and each meta-analysis was assessed by two pairs. We calculated raw percentage agreement and chance corrected agreement using Gwet's Agreement Coefficient (AC) in consensus judgments between pairs. RESULTS: Across the eight signaling questions in the ROB-ME tool, raw percentage agreement ranged from 52% to 100%, and Gwet's AC ranged from 0.39 to 0.76. For the risk-of-bias judgment, the raw percentage agreement was 76% (95% confidence interval 60% to 92%) and Gwet's AC was 0.47 (95% confidence interval 0.14 to 0.80). In seven (17%) meta-analyses, either one or both pairs judged the risk of bias due to missing evidence as "low risk". CONCLUSION: Our findings indicated substantial variation in assessments in consensus judgments between pairs for the signaling questions and overall risk-of-bias judgments. More tutorials and training are needed to help researchers apply the ROB-ME tool more consistently.

Should We Fix the Fibula in Tibial Plafond Fractures? A Meta-analysis Reviewing the Evidence Base for Fibula Open Reduction and Internal Fixation in Tibial Plafond Fractures.

Open reduction and internal fixation are the standard of care to stabilize tibial plafond fractures. However, it remains uncertain as to whether fixation of the fibula affects the outcome. This study aimed to review the evidence base for comparable outcomes in tibial plafond fractures when undergoing open reduction and internal fixation of ipsilateral fibula fractures compared with open reduction and internal fixation of the tibia alone. A systematic review and meta-analysis of the literature was completed; 4 studies were included for analysis. This study demonstrated no statistically significant differences in the incidence of nonunion (p = .784) or mal-union (p = .416). There was a greater rate of removal of metalwork in the fibula operative group compared to the tibia alone group (p < .001). The current evidence demonstrates that open reduction and internal fixation of ipsilateral fibula fractures in tibial plafond fractures is not necessarily routinely indicated for all fractures.

Hypermedia-based software architecture enables Test-Driven Development.

Objectives: Using agile software development practices, develop and evaluate an architecture and implementation for reliable and user-friendly self-service management of bioinformatic data stored in the cloud. Materials and methods: Comprehensive Oncology Research Environment (CORE) Browser is a new open-source web application for cancer researchers to manage sequencing data organized in a flexible format in Amazon Simple Storage Service (S3) buckets. It has a microservices- and hypermedia-based architecture, which we integrated with Test-Driven Development (TDD), the iterative writing of computable specifications for how software should work prior to development. Relying on repeating patterns found in hypermedia-based architectures, we hypothesized that hypermedia would permit developing test "templates" that can be parameterized and executed for each microservice, maximizing code coverage while minimizing effort. Results: After one-and-a-half years of development, the CORE Browser backend had 121 test templates and 875 custom tests that were parameterized and executed 3031 times, providing 78% code coverage. Discussion: Architecting to permit test reuse through a hypermedia approach was a key success factor for our testing efforts. CORE Browser's application of hypermedia and TDD illustrates one way to integrate software engineering methods into data-intensive networked applications. Separating bioinformatic data management from analysis distinguishes this platform from others in bioinformatics and may provide stable data management while permitting analysis methods to advance more rapidly. Conclusion: Software engineering practices are underutilized in informatics. Similar informatics projects will more likely succeed through application of good architecture and automated testing. Our approach is broadly applicable to data management tools involving cloud data storage.

Real-World User Demographics of Three Web-Based Digital Mental Health Interventions Provided by the US Department of Veterans Affairs: Observational Study Using Web Analytics Data.

BACKGROUND: Unguided digital mental health interventions (UDMHIs) have the potential to provide low-cost and effective mental health care at scale. Controlled trials have demonstrated the efficacy of UDMHIs to address mental health symptoms and conditions. However, few previous publications have described the demographics of real-world users of UDMHIs that are freely available to the public. The US Department of Veterans Affairs has created and hosts several UDMHIs on its Veteran Training Portal website. These web-based, free-to-use, and publicly available UDMHIs include Path to Better Sleep, Anger and Irritability Management Skills, and Moving Forward, which focus on insomnia, problematic anger, and depression symptoms, respectively. OBJECTIVE: This study aimed to examine the user demographics of these 3 UDMHIs in the year 2021. In addition, it aimed to compare the age and gender distribution of the users of those 3 UDMHIs with one another and with the age and gender distribution of the total US veteran population. METHODS: Google Analytics was used to collect user data for each of the 3 UDMHIs. The age and gender distribution of the users of each UDMHI was compared with that of the other UDMHIs as well as with that of the overall US veteran population using chi-square tests. Information on the total number of users, the country they were in, and the devices they used to access the UDMHIs was also collected and reported. RESULTS: In 2021, the 3 UDMHIs together recorded 29,306 unique users. The estimated age range and gender were available for 24.12% (7068/29,306) of those users. Each UDMHI's age and gender distribution significantly differed from that of the other UDMHIs and from that of the overall US veteran population (P<.001 on all chi-square tests). Women and younger age groups were overrepresented among UDMHI users compared with the overall US veteran population. The majority of devices used to access the UDMHIs were desktop or laptop devices, although a substantial proportion of devices used were mobile devices (10,199/29,752, 34.28%). Most users (27,789/29,748, 93.41%) were located in the United States, with users from Canada, the United Kingdom, and Australia accounting for another 2.61% (775/29,748) of total users. CONCLUSIONS: Our use of Google Analytics data provided useful information about the users of 3 free and publicly available UDMHIs provided by the US Department of Veterans Affairs. Although our findings should be considered in light of the limitations of autonomously collected web analytics data, they still offer useful information for health care policy makers, administrators, and UDMHI developers.

SAFoldNet: A Novel Tool for Discovering and Aligning Three-Dimensional Protein Structures Based on a Neural Network.

The development and improvement of methods for comparing and searching for three-dimensional protein structures remain urgent tasks in modern structural biology. To solve this problem, we developed a new tool, SAFoldNet, which allows for searching, aligning, superimposing, and determining the exact coordinates of fragments of protein structures. The proposed search and alignment tool was built using neural networking. Specifically, we implemented the integrative synergy of neural network predictions and the well-known BLAST algorithm for searching and aligning sequences. The proposed method involves multistage processing, comprising a stage for converting the geometry of protein structures into sequences of a structural alphabet using a neural network, a search stage for forming a set of candidate structures, and a refinement stage for calculating the structural alignment and overlap and evaluating the similarity with the starting structure of the search. The effectiveness and practical applicability of the proposed tool were compared with those of several widely used services for searching and aligning protein structures. The results of the comparisons confirmed that the proposed method is effective and competitive relative to the available modern services. Furthermore, using the proposed approach, a service with a user-friendly web interface was developed, which allows for searching, aligning, and superimposing protein structures; determining the location of protein fragments; mapping onto a protein molecule chain; and providing structural similarity metrices (expected value and root mean square deviation).

Randomized controlled trial of a group peer mentoring model for U.S. academic medicine research faculty.

Introduction: Midcareer is a critical transition point for biomedical research faculty and a common dropout point from an NIH-funded career. We report a study to assess the efficacy of a group peer mentoring program for diverse biomedical researchers in academic medicine, seeking to improve vitality, career advancement, and cross-cultural competence. Methods: We conducted a stratified randomized controlled trial with a waitlist control group involving 40 purposefully diverse early midcareer research faculty from 16 states who had a first-time NIH R01 (or equivalent) award, a K training grant, or a similar major grant. The yearlong intervention (2 to 3 days quarterly) consisted of facilitated, structured, group peer mentoring. Main study aims were to enhance faculty vitality, self-efficacy in achieving research success, career advancement, mentoring others, and cultural awareness and appreciation of diversity in the workplace. Results: Compared to the control group, the intervention group's increased vitality did not reach statistical significance (P = 0.20), but perceived change in vitality was 1.47 standard deviations higher (D = 1.47, P = 0.03). Self-efficacy for career advancement was higher in the intervention group (D = 0.41, P = 0.05) as was self-efficacy for research (D = 0.57, P = 0.02). The intervention group also valued diversity higher (D = 0.46, P = 0.02), had higher cognitive empathy (D = 0.85, P = 0.03), higher anti-sexism/racism skills (D = 0.71, P = 0.01), and higher self-efficacy in mentoring others (D = 1.14, P = 0.007). Conclusions: The mentoring intervention resulted in meaningful change in important dimensions and skills among a national sample of diverse early midcareer biomedical faculty. This mentoring program holds promise for addressing the urgencies of sustaining faculty vitality and cross-cultural competence.

Modeling Side Chains in the Three-Dimensional Structure of Proteins for Post-Translational Modifications.

Amino acid substitutions and post-translational modifications (PTMs) play a crucial role in many cellular processes by directly affecting the structural and dynamic features of protein interaction. Despite their importance, the understanding of protein PTMs at the structural level is still largely incomplete. The Protein Data Bank contains a relatively small number of 3D structures having post-translational modifications. Although recent years have witnessed significant progress in three-dimensional modeling (3D) of proteins using neural networks, the problem related to predicting accurate PTMs in proteins has been largely ignored. Predicting accurate 3D PTM models in proteins is closely related to another fundamental problem: predicting the correct side-chain conformations of amino acid residues in proteins. An analysis of publications as well as the paid and free software packages for modeling three-dimensional structures showed that most of them focus on working with unmodified proteins and canonical amino acid residues; the number of articles and software packages placing emphasis on modeling three-dimensional PTM structures is an order of magnitude smaller. This paper focuses on modeling the side-chain conformations of proteins containing PTMs (nonstandard amino acid residues). We collected our own libraries comprising the most frequently observed PTMs from the PDB and implemented a number of algorithms for predicting the side-chain conformation at modification points and in the immediate environment of the protein. A comprehensive analysis of both the algorithms per se and compared to the common Rosetta and FoldX structure modeling packages was also carried out. The proposed algorithmic solutions are comparable in their characteristics to the well-known Rosetta and FoldX packages for the modeling of three-dimensional structures and have great potential for further development and optimization. The source code of algorithmic solutions has been deposited to and is available at the GitHub source.

Application of EBMT, MASCC, and qSOFA Scores to Predict Complicated Febrile Neutropenia and Mortality in Autologous Stem Cell Transplant Recipients.

BACKGROUND AND OBJECTIVES: Three different scores were addressed as predictors of outcomes in autologous stem cell transplant (Auto SCT): one was calculated by pretransplant characteristics (European Society for Blood and Marrow Transplantation [EBMT] risk score), and two were calculated at the onset of febrile neutropenia (Multinational Association for Supportive Care in Cancer [MASCC] and Quick Sequential Organ Failure Assessment [qSOFA]). We considered bloodstream infection (BSI), carbapenem prescription, admission to the intensive care unit (ICU), and mortality as outcomes. PATIENTS: A total of 309 patients with a median age of 54 years were enrolled. RESULTS: Patients with EBMT score ≥4 (EBMT 4+) had higher ICU rates (14% vs. 4%; p < 0.01) and more carbapenem prescriptions (61% vs. 38%; p < 0.001) than those with EBMT score <4. MASCC <21 points (MASCC HR) was associated with carbapenem prescription (59% vs. 44%; p = 0.013), ICU (19% vs. 3%; p < 0.01), and death (4% vs. 0; p = 0.014). Patients with at least two points by qSOFA (qSOFA 2+) had more frequent BSI (55% vs. 22%; p = 0.03), ICU admissions (73% vs. 7; p < 0.01), and death (18% vs. 0.7, p = 0.02). EBMT 4+ and MASCC HR achieved the best sensitivities for ICU. For death, the best sensitivity was obtained with MASCC. CONCLUSION: In conclusion, risk scores for Auto SCT showed an association with outcomes and had different performances when combined or used alone. Therefore, risk scores for Auto SCT are useful in supportive care and clinical surveillance in stem cell transplant recipients.

Credibility at stake: only two-thirds of randomized trials of nutrition interventions are registered and lack transparency in outcome and treatment effect definitions.

OBJECTIVES: This study aimed to investigate the adherence of randomized controlled trials of nutrition interventions to transparency practices informing assessments of selective reporting biases, including the availability of a trial registration entry, protocol and statistical analysis plan (SAP). STUDY DESIGN AND SETTING: Retrospective observational study with cross-sectional design. We systematically searched for trials published from 1 July 2019, to 30 June 2020, and included a randomly selected sample of 400 studies. We searched for registry entries, protocols, and SAPs for all included studies. We extracted data to characterize the disclosure of sufficient information in the available materials to inform assessments of selective reporting biases, considering the definition of outcome domain, measure, metric, method of aggregation, time point, analysis population, methods to handle missing data and method of adjustment. RESULTS: Most trials (69%) were registered, but these often lacked sufficient specification of outcomes and intended treatment effects. Protocols and SAPs provided more details but were less often available (14% and 3%, respectively), and even then, almost all studies presented limited information to inform the assessments of risk of bias due to the selection of the reported result. CONCLUSION: Lack of full specification of outcomes and intended treatment effects hinder a full adherence of randomized controlled trials of nutrition interventions to transparency practices and may affect their credibility.

A unified model for the dynamics of ATP-independent ultrafast contraction.

In nature, several ciliated protists possess the remarkable ability to execute ultrafast motions using protein assemblies called myonemes, which contract in response to Ca2+ ions. Existing theories, such as actomyosin contractility and macroscopic biomechanical latches, do not adequately describe these systems, necessitating development of models to understand their mechanisms. In this study, we image and quantitatively analyze the contractile kinematics observed in two ciliated protists (Vorticella sp. and Spirostomum sp.), and, based on the mechanochemistry of these organisms, we propose a minimal mathematical model that reproduces our observations as well as those published previously. Analyzing the model reveals three distinct dynamic regimes, differentiated by the rate of chemical driving and the importance of inertia. We characterize their unique scaling behaviors and kinematic signatures. Besides providing insights into Ca2+-powered myoneme contraction in protists, our work may also inform the rational design of ultrafast bioengineered systems such as active synthetic cells.