Development and validation of interpretable machine learning models to predict glomerular filtration rate in chronic kidney disease Colombian patients.

BACKGROUND: ML predictive models have shown their capability to improve risk prediction and assist medical decision-making, nevertheless, there is a lack of accuracy systems to early identify future rapid CKD progressors in Colombia and even in South America. OBJECTIVE: The purpose of this study was to develop a series of interpretable machine learning models that predict GFR at 6-months, 9-months, and 12-months. STUDY DESIGN AND SETTING: Over 29,000 CKD patients stage 1 to 3b (estimated GFR, <60 mL/min/1.73 m2) with an average of 3-year follow-up data were included. We used the machine learning extreme gradient boosting (XGBoost) to build three models to predict the next eGFR. Models were internally and externally validated. In addition, we included SHapley Additive exPlanation (SHAP) values to offer interpretable global and local prediction models. RESULTS: All models showed a good performance in development and external validation. However, the 6-months XGBoost prediction model showed the best performance in internal (MAE average = 6.07; RSME = 78.87), and in external validation (MAE average = 6.45, RSME = 18.94). The top 3 most influential features that pushed the predicted eGFR value to lower values were the interpolated values for eGFR and creatinine, and eGFR at baseline. CONCLUSION: In the current study we have developed and validated machine learning models to predict the next eGFR value at different intervals. Furthermore, we attempted to approach the need for prediction explanation by offering transparent predictions.

Snapshot of knowledge and stigma toward mental health disorders and treatment in Spain.

Background: Mental disorders significantly impact individuals and societies globally. Addressing societal stigma is crucial, as it affects help-seeking behaviors and the effectiveness of treatment for mental disorders. Objective: This study aims to explore the knowledge and perceptions of the Spanish population toward mental disorders and their treatment, assess changes in mental health stigma over time, and examine variations across sociodemographic variables by comparing current results with previous studies. Methods: A panel of three psychiatrists designed a questionnaire to collect public opinions about various aspects of mental illness in Spain, covering topics such as social perception, diagnostic reliability, causes, symptoms, treatment, suicide, and media influence. The survey, conducted from October to December 2022, involved 1,002 Spanish individuals aged 18-70. Results: Our results indicated an improved general knowledge of mental health, reduced stigma, and greater acceptance of those affected by these disorders, compared to past research. Almost 80% of the participants have accurate knowledge regarding the complex and multifactorial nature of mental illnesses. Around 90% of the participants share the belief that stigma affects those affected by mental disorders. Psychological and pharmacological treatment are considered to be effective and helpful by more than 70% of the sample. More than 60% of the participants highlighted that suicide needs to be addressed appropriately in the media. Conclusion: These findings suggest a significant shift in how Spanish society views mental disorders, marking progress over decades of discrimination. Reducing the stigma associated with mental health can encourage individuals to seek assistance without the fear of judgment or discrimination, thereby increasing the likelihood of early intervention and treatment. Open conversations about mental health within families, communities, and workplaces can create a supportive environment that enhances recovery. However, continued efforts and awareness campaigns targeted to broader audiences remain necessary. Responsible media portrayals of mental health, avoiding stigmatizing language or sensationalism, are also essential.

Negotiating and Treating Lateral Canals: Report of 7 Cases.

This is a series of 7 cases in which the operator penetrated lateral canals with instruments. Two teeth presented with irreversible pulpitis, 4 with necrotic pulps, and 1 with previous treatment. Except for the teeth with pulpitis, all the others were associated with apical periodontitis. The main root canal was always relatively straight, with the lateral canals at the middle third of the root. Suggestive images of lateral canal presence were seen on periapical radiographs in five cases. The clinician introduced intentionally small hand instruments in the lateral canal in 5 cases, while the penetration was fortuitous in the others. The lateral canals were obturated in all cases. Follow-up examination was possible in five cases, all of them showed evidence of successful clinical and radiographic outcomes. Introducing files into lateral canals may permit some preparation and penetration of irrigant solution, favoring disinfection and, consequently, enhancing the treatment outcome. (EEJ-2023-05-063).

Trauma center rehabilitation systems in Latin America.

Trauma is a leading cause of mortality and morbidity worldwide with high rates of disability in survivors. With improvements in care, rehabilitation of the trauma patient is a cornerstone to reducing sequelae. A lack of well-established hospital rehabilitation units and standardized protocols for managing posttraumatic injuries is a common problem in Latin American countries. Future studies should seek to understand the barriers and gaps in care so that consensus and ultimately best practice guidelines can be developed and included in rehabilitation programs throughout trauma centers in Latin America.

Highly efficient mobility, separation and charge transfer in black SnO2-TiO2 structures with co-catalysts: the key step for the photocatalytic hydrogen evolution.

Oxygen vacancies and co-catalysts enhance photocatalytic hydrogen production by improving the charge carrier separation. Herein, the black SnO2-TiO2 structure (BST) was synthesized for the first time by two consecutive methods. First, the sol-gel nucleation method allowed TiO2 to form on the SnO2 nanoparticles, creating a strong interaction and direct contact between them. Subsequently, this structure was reduced by NaBH4 during thermal treatment, generating (Ti3+/Sn2+) states to form the BST. Then, 2 wt% of Co, Cu or Pd was impregnated onto BST. The results showed that the activity raised with the presence of Ti3+/Sn2+ states, reaching a hydrogen generation rate of 147.50 µmol g-1 h-1 with BST in comparison with the rate of 99.50 µmol g-1 h-1 for white SnO2-TiO2. On the other hand, the interaction of the co-catalysts with the BST structure helped to increase the photocatalytic hydrogen production rates: 154.10 µmol g-1 h-1, 384.18 µmol g-1 h-1 and 480.20 µmol g-1 h-1 for cobalt-BST, copper-BST and palladium-BST, respectively. The results can be associated with the creation of Ti3+/Sn2+ at the BST interface that changes the lifetime of the charge carrier, improving the separation of photogenerated electrons and holes and the co-catalysts in the structures move the flat band position and increasing the photocurrent response to having electrons with greater reducing power.

Compassionate use of esketamine intranasal in patients with severe major depressive disorder resistant to the treatment.

BACKGROUND: Treatment-resistant depression (TRD) is defined as the failure of at least two antidepressants in adequate doses and timing during a major depressive episode. Esketamine intranasal (ESK-IN) has been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of TRD in combination with other antidepressants. AIMS: To assess the effectiveness and tolerability of a sample of TRD patients who received treatment with ESK-IN as part of the compassionate use program. METHODS: A retrospective, observational study was carried out on patients with a diagnosis of TRD enrolled in the early access program of ESK-IN in nine centers. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS) at four time points: baseline, 28, 90, and 180 days of treatment. RESULTS: The sample included 71 patients (70% women) with a mean baseline MADRS score of 38.27 ± 5.9 and total or partial work disability rates of 85%. ESK-IN treatment was associated with a statistically and clinically significant reduction in the severity of depressive symptoms at all time points assessed. The presence of side effects was common but the majority were mild in severity and resolved after the observation period. Those patients who received psychotherapy in combination with ESK-IN showed a significantly lower MADRS score at 90 and 180 days than those patients who did not undergo psychotherapy. CONCLUSION: ESK-IN has proven to be effective and safe in a clinical sample of patients with severe TRD. To optimize clinical outcomes, the pharmacological treatment for TRD should always be integrated into a comprehensive therapeutic plan that encompasses strategies such as psychotherapy, social support, and family interventions.

Isolation and Characterization of Two Novel Genera of Jumbo Bacteriophages Infecting Xanthomonas vesicatoria Isolated from Agricultural Regions in Mexico.

Bacterial spot is a serious disease caused by several species of Xanthomonas affecting pepper and tomato production worldwide. Since the strategies employed for disease management have been inefficient and pose a threat for environmental and human health, the development of alternative methods is gaining relevance. The aim of this study is to isolate and characterize lytic phages against Xanthomonas pathogens. Here, we isolate two jumbo phages, named XaC1 and XbC2, from water obtained from agricultural irrigation channels by the enrichment technique using X. vesicatoria as a host. We determined that both phages were specific for inducing the lysis of X. vesicatoria strains, but not of other xanthomonads. The XaC1 and XbC2 phages showed a myovirus morphology and were classified as jumbo phages due to their genomes being larger than 200 kb. Phylogenetic and comparative analysis suggests that XaC1 and XbC2 represent both different and novel genera of phages, where XaC1 possesses a low similarity to other phage genomes reported before. Finally, XaC1 and XbC2 exhibited thermal stability up to 45 °C and pH stability from 5 to 9. All these results indicate that the isolated phages are promising candidates for the development of formulations against bacterial spot, although further characterization is required.

Screen exposure, mental health and emotional well-being in the adolescent population: is it time for governments to take action?

During the last decade, a multitude of epidemiological studies with different designs have been published assessing the association between the use of digital media and psychological well-being, including the incidence of mental disorders and suicidal behaviours. Particularly, available research has very often focused on smartphone use in teenagers, with highly addictive potential, coining the term 'problematic smartphone use' and developing specific scales to measure the addictive or problematic use of smartphones. Available studies, despite some methodological limitations and gaps in knowledge, suggest that higher screen time is associated with impaired psychological well-being, lower self-esteem, higher levels of body dissatisfaction, higher incidence of eating disorders, poorer sleeping outcomes and higher odds of depressive symptoms in adolescents. Moreover, a significant association has also been found between screen time and higher suicide risk. Finally, problematic pornography has been shown to be highly prevalent and it is a strong cause of concern to many public health departments and national governments because it might be eventually associated with aggressive sexual behaviours.

Integrating Proteomics and Metabolomics Approaches to Elucidate the Mechanism of Responses to Combined Stress in the Bell Pepper (Capsicum annuum).

Bell pepper plants are sensitive to environmental changes and are significantly affected by abiotic factors such as UV-B radiation and cold, which reduce their yield and production. Various approaches, including omics data integration, have been employed to understand the mechanisms by which this crop copes with abiotic stress. This study aimed to find metabolic changes in bell pepper stems caused by UV-B radiation and cold by integrating omic data. Proteome and metabolome profiles were generated using liquid chromatography coupled with mass spectrometry, and data integration was performed in the plant metabolic pathway database. The combined stress of UV-B and cold induced the accumulation of proteins related to photosynthesis, mitochondrial electron transport, and a response to a stimulus. Further, the production of flavonoids and their glycosides, as well as affecting carbon metabolism, tetrapyrrole, and scopolamine pathways, were identified. We have made the first metabolic regulatory network map showing how bell pepper stems respond to cold and UV-B stress. We did this by looking at changes in proteins and metabolites that help with respiration, photosynthesis, and the buildup of photoprotective and antioxidant compounds.

Is There a Relationship of Cortisol and Sex Steroid Hormones With Mental Health in Middle-Aged Adults? The FIT-AGEING Study.

OBJECTIVE: Mental health has emerged as a worldwide concern given the increasing incidence of anxiety and depression disorders in the last years. Cortisol and sex steroid hormones have been demonstrated to be important regulators of mental health processes in older adults. However, the evidence considering these integrated variables in apparently healthy middle-aged individuals has not been thoroughly addressed. The present study aimed to investigate the association of the plasma cortisol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) levels with mental health in middle-aged adults. METHODS: This cross-sectional study included a cohort of 73 middle-aged adults aged 45 to 65 years (women, 53%). Plasma cortisol, testosterone, SHBG, and DHEAS were assessed using a competitive chemiluminescence immunoassay. Free testosterone was calculated from the total testosterone and SHBG. Self-reported depression severity, generic health-related quality of life, hope, satisfaction with life, and optimism-pessimism were evaluated using the Beck Depression Inventory-II (BDI-II), 36-Item Short-Form Health Survey, Adult Hope Scale, Satisfaction with Life Scale, and Life Orientation Test-Revised, respectively-with higher total scores of these scales indicating greater levels of these variables. RESULTS: The testosterone and free testosterone levels were inversely associated with the BDI-II values in men (all P ≤ .042). The cortisol levels were positively related with the Satisfaction with Life Scale scores, whereas the testosterone, free testosterone, SHBG, and DHEAS levels were negatively correlated with the BDI-II values in women (all P ≤ .045). CONCLUSION: In summary, these results suggest that the increased levels of steroid hormones-within the normal values-are associated with better mental health in middle-aged adults.

Correlation and comparison between different measurement sites of waist circumference and cardiovascular risk in children: a systematic review and meta-analysis.

BACKGROUND: waist circumference (WC) is a component of metabolic syndrome (MetS) and an excellent marker for the risk of cardiovascular disease (CVD) in children. This study aimed to provide information on the anatomical measurement sites of WC and their comparative correlation with MetS and its components in children. METHODS: the literature search included papers published between January 2005 and September 2023 that met the following criteria: pediatric patients (2-18 years), WC measurement at different anatomical sites (≥ 2), and CVD risk by MetS. The quality of each study was determined using the STROBE and modified GRADE scales. The meta-analysis evaluated the WCiliac-crest and WCmiddle. RESULTS: five observational studies (total population: 1,224) were included. WC was measured at 2-4 anatomical sites. In all studies, the correlations between different WC measurement sites and CVD risk were similar. The STROBE assessment ranged from 12-20/22 and the GRADE was A for all the articles. The meta-analysis showed that the heterogeneity (I2 test) of the WCiliac-crest and WCmiddle with CVD variables was substantial. CONCLUSION: All WC measurement sites showed adequate correlation with CVD risk, with some small individual differences. WCnarrow and WCumbilucus have adequate consistency and could be excellent alternatives in daily clinical practice because of their ease of measurement. Further studies are needed to evaluate the correlation between different WC measurement sites and CVD risk in children stratified according to pubertal stage and sex.

Clinical decision-making before discharge in hospitalized persons with schizophrenia: a Spanish Delphi expert consensus.

Introduction: The care of people with schizophrenia (PWS) is usually provided in an outpatient setting by community mental health teams. However, PWS frequently require inpatient treatment because of a wide array of clinical, personal and/or social situations. Unfortunately, to our knowledge, there are no guidelines available to help psychiatrists in the decision-making process on hospital discharge for PWS. The aim of this project was to develop an expert consensus on discharge criteria for PWS after their stay in an acute inpatient psychiatric unit. Methods: Using a modified Delphi method a group of 42 psychiatrists throughout Spain evaluated four areas of interest regarding this issue: clinical symptomatology, treatment-related factors, follow-up health care units after discharge, and physical health and monitoring. Results: After two rounds, among the 64 statements, a consensus was reached for 59 (92.2%) statements. In three (17.7%) of the 17 statements on 'clinical symptomatology' and 2 (13.3%) of the 15 statements on 'follow-up health care units after discharge', a consensus was not reached; in contrast, a consensus was reached for all statements concerning 'treatment-related factors' and those concerning 'physical health and monitoring'. The consensus results highlight the importance for discharge of the control of symptoms rather than their suppression during admission and of tolerability in the selection of anantipsychotic. Discussion: Although there is a lack of relevant data for guiding the discharge of PWS after hospitalization in an acute inpatient psychiatric unit, we expect that this consensus based on expert opinion may help clinicians to take appropriate decisions.

Neurodegenerative Diseases: Unraveling the Heterogeneity of Astrocytes.

The astrocyte population, around 50% of human brain cells, plays a crucial role in maintaining the overall health and functionality of the central nervous system (CNS). Astrocytes are vital in orchestrating neuronal development by releasing synaptogenic molecules and eliminating excessive synapses. They also modulate neuronal excitability and contribute to CNS homeostasis, promoting neuronal survival by clearance of neurotransmitters, transporting metabolites, and secreting trophic factors. Astrocytes are highly heterogeneous and respond to CNS injuries and diseases through a process known as reactive astrogliosis, which can contribute to both inflammation and its resolution. Recent evidence has revealed remarkable alterations in astrocyte transcriptomes in response to several diseases, identifying at least two distinct phenotypes called A1 or neurotoxic and A2 or neuroprotective astrocytes. However, due to the vast heterogeneity of these cells, it is limited to classify them into only two phenotypes. This review explores the various physiological and pathophysiological roles, potential markers, and pathways that might be activated in different astrocytic phenotypes. Furthermore, we discuss the astrocyte heterogeneity in the main neurodegenerative diseases and identify potential therapeutic strategies. Understanding the underlying mechanisms in the differentiation and imbalance of the astrocytic population will allow the identification of specific biomarkers and timely therapeutic approaches in various neurodegenerative diseases.

Alpha-Synuclein Gene Alterations Modulate Tyrosine Hydroxylase in Human iPSC-Derived Neurons in a Parkinson's Disease Animal Model.

Parkinson's disease (PD) caused by SNCA gene triplication (3XSNCA) leads to early onset, rapid progression, and often dementia. Understanding the impact of 3XSNCA and its absence is crucial. This study investigates the differentiation of human induced pluripotent stem cell (hiPSC)-derived floor-plate progenitors into dopaminergic neurons. Three different genotypes were evaluated in this study: patient-derived hiPSCs with 3XSNCA, a gene-edited isogenic line with a frame-shift mutation on all SNCA alleles (SNCA 4KO), and a normal wild-type control. Our aim was to assess how the substantia nigra pars compacta (SNpc) microenvironment, damaged by 6-hydroxydopamine (6-OHDA), influences tyrosine hydroxylase-positive (Th+) neuron differentiation in these genetic variations. This study confirms successful in vitro differentiation into neuronal lineage in all cell lines. However, the SNCA 4KO line showed unusual LIM homeobox transcription factor 1 alpha (Lmx1a) extranuclear distribution. Crucially, both 3XSNCA and SNCA 4KO lines had reduced Th+ neuron expression, despite initial successful neuronal differentiation after two months post-transplantation. This indicates that while the SNpc environment supports early neuronal survival, SNCA gene alterations-either amplification or knock-out-negatively impact Th+ dopaminergic neuron maturation. These findings highlight SNCA's critical role in PD and underscore the value of hiPSC models in studying neurodegenerative diseases.

Writing to Keep on Living: A Systematic Review and Meta-Analysis on Creative Writing Therapy for the Management of Depression and Suicidal Ideation.

PURPOSE OF REVIEW: The purpose of this review and meta-analysis was to explore the effectiveness of creative writing therapies for the management of depression and suicidal ideation. RECENT FINDINGS: Twenty one of the 31 reviewed studies showed that creative writing significantly improved depressive symptoms, while five studies suggested improvement in other symptoms. The results of meta-analyses showed that narrative writing significantly reduced depression compared to those in neutral writing or treatment as usual condition in both post intervention and follow-up. However, the number of studies exploring the effects of creative writing in suicidal ideation was too low to perform a meta-analysis. A structured and well-targeted intervention using creative writing could have beneficial results for the management of depressive symptoms. More studies are needed to explore the potential benefits of creative writing for reducing suicidal ideation.

Low lung function in Bipolar Disorder and Schizophrenia: a hidden risk.

Introduction: People with serious mental illness (SMI), such as schizophrenia and bipolar disorder, have a higher risk of premature morbidity and mortality. In the general population, impaired lung function is associated with increased morbidity and mortality. We compared lung function between people with and without serious mental illnesses using a cross-sectional study in 9 community mental health units. Methods: Subjects aged 40-70 years with a diagnosis of schizophrenia or bipolar disorder were recruited consecutively. The controls had no psychiatric diagnosis and were not receiving any psychotropics. Spirometry was performed by a trained nurse. We used the 2021 American Thoracic Society/European Respiratory Society standards for the interpretation of the spirometry results. Results: We studied 287 subjects. People with SMI (n = 169) had lower spirometry values than those without a psychiatric diagnosis (n = 118). An abnormal spirometry pattern (36.1% vs 16.9%, p < 0.001), possible restriction or non-specific (Preserved Ratio Impaired Spirometry [PRISm]) pattern (17.8% vs 7.6%, p = 0.014), and pattern of airflow obstruction or possible mixed disorder (18.3% vs 9.3%, p = 0.033) were more frequent in people with SMI. Multivariate analyses showed that the PRISm pattern was associated with abdominal circumference (odds ratio [OR] 1.05, 95%CI 1.03-1.08) and that the pattern of airflow obstruction or possible mixed disorder was associated with smoking behavior (OR 5.15, 95%CI 2.06-15.7). Conclusion: People with SMI have impaired lung function, with up to one-third of them showing an abnormal spirometry pattern. This suggests that regular monitoring of lung function and addressing modifiable risk factors, such as tobacco use and obesity, in this population is of paramount importance.

Public perception of psychiatry, psychology and mental health professionals: a 15-year analysis.

Background: X (previously known as "Twitter") serves as a platform for open discussions on mental health, providing an avenue for scrutinizing public perspectives regarding psychiatry, psychology and their associated professionals. Objective: To analyze the conversations happening on X about psychiatrists, psychologists, and their respective disciplines to understand how the public perception of these professionals and specialties has evolved over the last 15 years. Methods: We collected and analyzed all tweets posted in English or Spanish between 2007 and 2023 referring to psychiatry, psychology, neurology, mental health, psychiatrist, psychologist, or neurologist using advance topic modelling and sentiment analysis. Results: A total of 403,767 tweets were analyzed, 155,217 (38%) were in English and 248,550 (62%) in Spanish. Tweets about mental health and mental health professionals and disciplines showed a consistent volume between 2011 and 2016, followed by a gradual increase from 2016 through 2022. The proportion of tweets discussing mental health doubled from 2016 to 2022, increasing from 20% to 67% in Spanish and from 15% to 45% in English. Several differences were observed on the volume of tweets overtime depending on the language they were written. Users associated each term with varied topics, such as seeking for help and recommendation for therapy, self-help resources, medication and side effects, suicide prevention, mental health in times of crisis, among others. The number of tweets mentioning these topics increased by 5-10% from 2016 to 2022, indicating a growing interest among the population. Emotional analysis showed most of the topics were associated with fear and anger. Conclusion: The increasing trend in discussions about mental health and the related professionals and disciplines over time may signify an elevated collective awareness of mental health. Gaining insights into the topics around these matters and user's corresponding emotions towards them presents an opportunity to combat the stigma surrounding mental health more effectively.

Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial.

BACKGROUND: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38ß MAPK) for the treatment of facioscapulohumeral muscular dystrophy. METHODS: We did a randomised, double-blind, placebo-controlled phase 2b trial at 17 neurology centres in Canada, France, Spain, and the USA. We included adults aged 18-65 years with type 1 facioscapulohumeral muscular dystrophy (ie, with loss of repression of DUX4 expression, as ascertained by genotyping), a Ricci clinical severity score of 2-4, and at least one skeletal muscle judged using MRI to be suitable for biopsy. Participants were randomly allocated (1:1) to either oral losmapimod (15 mg twice a day) or matching placebo for 48 weeks, via an interactive response technology system. The investigator, study staff, participants, sponsor, primary outcome assessors, and study monitor were masked to the treatment allocation until study closure. The primary endpoint was change from baseline to either week 16 or 36 in DUX4-driven gene expression in skeletal muscle biopsy samples, as measured by quantitative RT-PCR. The primary efficacy analysis was done in all participants who were randomly assigned and who had available data for assessment, according to the modified intention-to-treat principle. Safety and tolerability were assessed as secondary endpoints. This study is registered at ClinicalTrials.gov, number NCT04003974. The phase 2b trial is complete; an open-label extension is ongoing. FINDINGS: Between Aug 27, 2019, and Feb 27, 2020, 80 people were enrolled. 40 were randomly allocated to losmapimod and 40 to placebo. 54 (68%) participants were male and 26 (33%) were female, 70 (88%) were White, and mean age was 45·7 (SD 12·5) years. Least squares mean changes from baseline in DUX4-driven gene expression did not differ significantly between the losmapimod (0·83 [SE 0·61]) and placebo (0·40 [0·65]) groups (difference 0·43 [SE 0·56; 95% CI -1·04 to 1·89]; p=0·56). Losmapimod was well tolerated. 29 treatment-emergent adverse events (nine drug-related) were reported in the losmapimod group compared with 23 (two drug-related) in the placebo group. Two participants in the losmapimod group had serious adverse events that were deemed unrelated to losmapimod by the investigators (alcohol poisoning and suicide attempt; postoperative wound infection) compared with none in the placebo group. No treatment discontinuations due to adverse events occurred and no participants died during the study. INTERPRETATION: Although losmapimod did not significantly change DUX4-driven gene expression, it was associated with potential improvements in prespecified structural outcomes (muscle fat infiltration), functional outcomes (reachable workspace, a measure of shoulder girdle function), and patient-reported global impression of change compared with placebo. These findings have informed the design and choice of efficacy endpoints for a phase 3 study of losmapimod in adults with facioscapulohumeral muscular dystrophy. FUNDING: Fulcrum Therapeutics.

AgTC and AgETL: open-source tools to enhance data collection and management for plant science research.

Advancements in phenotyping technology have enabled plant science researchers to gather large volumes of information from their experiments, especially those that evaluate multiple genotypes. To fully leverage these complex and often heterogeneous data sets (i.e. those that differ in format and structure), scientists must invest considerable time in data processing, and data management has emerged as a considerable barrier for downstream application. Here, we propose a pipeline to enhance data collection, processing, and management from plant science studies comprising of two newly developed open-source programs. The first, called AgTC, is a series of programming functions that generates comma-separated values file templates to collect data in a standard format using either a lab-based computer or a mobile device. The second series of functions, AgETL, executes steps for an Extract-Transform-Load (ETL) data integration process where data are extracted from heterogeneously formatted files, transformed to meet standard criteria, and loaded into a database. There, data are stored and can be accessed for data analysis-related processes, including dynamic data visualization through web-based tools. Both AgTC and AgETL are flexible for application across plant science experiments without programming knowledge on the part of the domain scientist, and their functions are executed on Jupyter Notebook, a browser-based interactive development environment. Additionally, all parameters are easily customized from central configuration files written in the human-readable YAML format. Using three experiments from research laboratories in university and non-government organization (NGO) settings as test cases, we demonstrate the utility of AgTC and AgETL to streamline critical steps from data collection to analysis in the plant sciences.

Mapping Human Resources to Guide Ophthalmology Capacity-Building Projects in Honduras: Sub-national Analyses of Physician Distribution and Surgical Practices.

Objective: To map ophthalmologist locations and surgical practices as they vary sub-nationally within Honduras to maximize the impact of efforts to develop cataract surgical capacity. Methods: An anonymous survey was sent to all Honduran ophthalmologists with questions on surgical volume, department-level location, type of facility in which they work, surgical methods, and age. Surgical volume, population, and poverty data sourced through the Oxford Poverty Human Development Initiative were mapped at the department level, and cataract surgical rates (CSR; surgeries per million population per year) were calculated and mapped. Results: Sixty-one of the 102 Honduran ophthalmologists contacted responded. Of those, 85% perform cataract surgery, and 49% work at least part time in a non-profit or governmental facility. Honduras has fewer surgical ophthalmologists per million than the global average, and though national CSR appears to be increasing, it varies significantly between departments. The correlation between CSR and poverty is complex, and outliers provide valuable insights. Conclusion: Mapping ophthalmological surgical practices as they relate to population and poverty at a sub-national level provides important insights into geographic trends in the need for and access to eye care. Such insights can be used to guide efficient and effective development of cataract surgical capacity.