Creating Culturally Adapted Multilingual Materials for Research.

Patients who speak languages other than English are frequently excluded from research. This exclusion exacerbates inequities, biases results, and may violate federal regulations and research ethics. Language justice is the right to communicate in an individual's preferred language to address power imbalances and promote equity. To promote language justice in research, we propose a method to translate and culturally-adapt multifaceted research materials into multiple languages simultaneously. Our method involves a multistep approach, including professional translation, review by bilingual expert panels to refine and reach consensus, and piloting or cognitive interviews with patients and families. Key differences from other translation approaches (eg, the World Health Organization) include omitting back-translation, given its limited utility in identifying translation challenges, and limiting expert panelist and piloting-participant numbers for feasibility. We detail a step-by-step approach to operationalizing this method and outline key considerations learned after utilizing this method to translate materials into 8 languages other than English for an ongoing multicenter pediatric research study on family safety-reporting. Materials included family brochures, surveys, and intervention materials. This approach took ∼6 months overall at a cost of <$2000 per language (not including study personnel costs). Key themes across the project included (1) tailor scope to timeline, budget, and resources, (2) thoughtfully design English source materials, (3) identify and apply guiding principles throughout the translation and editing process, and (4) carefully review content and formatting to account for nuances across multiple languages. This method balances feasibility and rigor in translating participant-facing materials into multiple languages simultaneously, advancing language justice in research.

A new avenue for molecular glues: Rapid discovery of a NFKB1 degrader.

Targeted protein degradation using molecular glues is a powerful method for targeting traditionally undruggable proteins. One challenge in molecular glue discovery is the absence of rational discovery methods. Here, King et al. leverage covalent library screening with chemoproteomics platforms to rapidly discover a molecular glue targeting NFKB1 via UBE2D recruitment.

AmericasNLI: Machine translation and natural language inference systems for Indigenous languages of the Americas.

Little attention has been paid to the development of human language technology for truly low-resource languages-i.e., languages with limited amounts of digitally available text data, such as Indigenous languages. However, it has been shown that pretrained multilingual models are able to perform crosslingual transfer in a zero-shot setting even for low-resource languages which are unseen during pretraining. Yet, prior work evaluating performance on unseen languages has largely been limited to shallow token-level tasks. It remains unclear if zero-shot learning of deeper semantic tasks is possible for unseen languages. To explore this question, we present AmericasNLI, a natural language inference dataset covering 10 Indigenous languages of the Americas. We conduct experiments with pretrained models, exploring zero-shot learning in combination with model adaptation. Furthermore, as AmericasNLI is a multiway parallel dataset, we use it to benchmark the performance of different machine translation models for those languages. Finally, using a standard transformer model, we explore translation-based approaches for natural language inference. We find that the zero-shot performance of pretrained models without adaptation is poor for all languages in AmericasNLI, but model adaptation via continued pretraining results in improvements. All machine translation models are rather weak, but, surprisingly, translation-based approaches to natural language inference outperform all other models on that task.

Evaluation of a Virtual Team-Based Project Designed to Improve Chronic Wound Patient Care in Ontario, Canada.

OBJECTIVE: To evaluate the effectiveness of the Extension for Community Healthcare Outcomes Ontario Skin and Wound Care project, a virtual team-based endeavor designed to improve the care of patients with chronic wounds. METHODS: The study team conducted phone interviews with healthcare professionals (n = 8) regarding their patients (n = 10). The management recommendations were grouped, and the study participants questioned concerning the implementation of the recommendations. Interviews were recorded and transcribed, and the transcripts were analyzed for common themes. The Queen's University Research Ethics Board approved this study. RESULTS: Interviews documented improvement in 50% of patients; the other half of the patients did not improve because of patient- and healthcare-system barriers. Three of five nonhealing patients were nonadherent regarding compression, and only one of six suggested biopsies were carried out. The investigators noted three primary reasons for the lack of recommendation implementation: (1) could not obtain a diagnostic procedure, (2) lack of a diagnosis, and (3) patient was reluctant to make a lifestyle change. Major themes included problems in care coordination and suboptimal patient and provider education, along with other obstacles to management. CONCLUSIONS: Participants stated that the project provided a beneficial learning experience. The findings highlighted a lack of integrated and coordinated interprofessional chronic wound care.

Chinese medical students' disposition for critical thinking: a mixed methods exploration.

BACKGROUND: Critical thinking (CT) is an essential competency for medical students. This study's aim was to evaluate Chinese medical students' disposition for CT and to explore the impact of current trends in medical education on students' CT development. METHODS: We used multistage stratified cluster sampling to recruit a total of 1241 medical students among five different years of training and from three medical institutions in China. The Critical Thinking Disposition Inventory-Chinese Version (CTDI-CV) and self-reported information were used to collect cross-sectional data. Based on the data from the CTDI-CV, 112 medical students in clinical course training from a single institution continued one-year follow-up. Their one-year CTDI-CV score changes were collected regarding various medical education variables. RESULTS: The mean CTDI-CV score of the 1241 medical students was 287.04 with 729 (58.7%) students receiving a score of 280 or higher. There were statistically significant differences in schools attended(F = 3.84, P < 0.05), year of school attended(F = 10.32, P < 0.001), GPA(F = 6.32, P < 0.01), weekly time spent learning after class(F = 14.14, P < 0.001), attitude toward medicine(F = 28.93, P < 0.001), desire to be a doctor after graduation(t = - 3.35, P < 0.001), familiarity with CT(F = 20.40, P < 0.001), and perception of importance of CT(F = 22.25, P < 0.001). The participants scored the highest on the CTDI-CV subscales of "inquisitiveness" and the lowest on "truth seeking." The 112 students in the longitudinal study had significantly lower total CT scores after one academic year follow-up. CONCLUSIONS: Chinese medical students generally exhibited positive CT dispositions. The cross-sectional survey and one-year longitudinal study indicated that students' CT disposition diminished as they progressed through traditional medical training. Our study contributes to understanding the status of Chinese medical education of and influential factors on medical students' CT disposition.

Inhibitors of Eukaryotic Translational Machinery as Therapeutic Agents.

Inhibiting eukaryotic protein translation with small molecules is emerging as a powerful therapeutic strategy. The advantage of targeting cellular translational machinery is that it is required for the highly proliferative state of many neoplastic cells, replication of certain viruses, and ultimately the expression of a wide variety of protein targets. Although, this approach has been exploited to develop clinical agents, such as homoharringtonine (HHT, 1), used to treat chronic myeloid leukemia (CML), inhibiting components of the translational machinery is often associated with cytotoxic phenotypes. However, recent studies have demonstrated that certain small molecules can inhibit the translation of specific subsets of proteins, leading to lower cytotoxicity, and opening-up therapeutic opportunities for translation inhibitors to be deployed in indications beyond oncology and infectious disease. This review summarizes efforts to develop inhibitors of the eukaryotic translational machinery as therapeutic agents and highlights emerging opportunities for translation inhibitors in the future.

Genomics Analysis of L-DOPA Exposure in Drosophila sechellia.

Drosophila sechellia is a dietary specialist fruit fly that evolved from a generalist ancestor to specialize on the toxic fruit of Morinda citrifolia This species pair has been the subject of numerous studies where the goal has largely been to determine the genetic basis of adaptations associated with host specialization. Because one of the most striking features of M. citrifolia fruit is the production of toxic volatile compounds that kill insects, most genomic studies in D. sechellia to date have focused on gene expression responses to the toxic compounds in its food. In this study, we aim to identify new genes important for host specialization by profiling gene expression response to 3,4-dihydroxyphenylalanine (L-DOPA). Recent work found it to be highly abundant in M. citrifolia, critical for reproductive success of D. sechellia, and supplementation of diet with the downstream pathway product dopamine can influence toxin resistance phenotypes in related species. Here we used a combination of functional genetics and genomics techniques to identify new genes that are important for D. sechellia ecological adaptation to this new niche. We show that L-DOPA exposure can affect toxin resistance phenotypes, identify genes with plastic responses to L-DOPA exposure, and functionally test an identified candidate gene. We found that knock-down of Esterase 6 (Est6) in a heterologous species alters toxin resistance suggesting Est6 may play an important role in D. sechellia host specialization.

Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein.

The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the ß5-ß6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.

Physician Scientist Training in the United States: A Survey of the Current Literature.

The declining number of physician scientists is an alarming issue. A systematic review of all existing programs described in the literature was performed, so as to highlight which programs may serve as the best models for the training of successful physician scientists. Multiple databases were searched, and 1,294 articles related to physician scientist training were identified. Preference was given to studies that looked at number of confirmed publications and/or research grants as primary outcomes. Thirteen programs were identified in nine studies. Eighty-three percent of Medical Scientist Training Program (MSTP) graduates, 77% of Clinician Investigator Training Program (CI) graduates, and only 16% of Medical Fellows Program graduates entered a career in academics. Seventy-eight percent of MSTP graduates succeeded in obtaining National Institute of Health (NIH) grants, while only 15% of Mayo Clinic National Research Service Award-T32 graduates obtained NIH grants. MSTP physician scientists who graduated in 1990 had 13.5 ± 12.5 publications, while MSTP physician scientists who graduated in 1975 had 51.2 ± 38.3 publications. Additionally, graduates from the Mayo Clinic's MD-PhD Program, the CI Program, and the NSRA Program had 18.2 ± 20.1, 26.5 ± 24.5, and 17.9 ± 26.3 publications, respectively. MSTP is a successful model for the training of physician scientists in the United States, but training at the postgraduate level also shows promising outcomes. An increase in the number of positions available for training at the postgraduate level should be considered.

Analysis of curricular reform practices at Chinese medical schools.

BACKGROUND: A comprehensive search of the literature published between 2001 and 2010 was performed to gain a greater understanding of curricular reform practices at Chinese medical schools. SUMMARY: There were 10,948 studies published between 2001 and 2010 that were retrieved from the database. Following preliminary screening, 76 publications from 49 different medical schools were selected. Thirty-one publications regarding clinical medicine curricular reforms were analyzed further. Of the 76 studies, 53 described curricular reforms that were instituted in theoretical courses, 22 described curricular reforms that were instituted in experimental courses, and 1 described curricular reforms that were instituted in a clinical skills training course. Of the 31 clinical medicine publications, 2 described reforms that were implemented for 3-year program medical students, 12 described reforms that were implemented for 5-year program medical students, 6 described reforms that were implemented for 7-year program medical students, and 2 described reforms that were implemented for 8-year program medical students. Currently, the majority of medical schools in China use the discipline-based curriculum model. Thirteen studies described transition to an organ-system-based curriculum model, 1 study described transition to a problem-based curriculum model, and 3 studies described transition to a clinical presentation-based curriculum model. In 7 studies educators decided to retain the discipline-based curriculum model while integrating 1 or several new courses to remedy the weaker aspects of the traditional curriculum, in 7 studies educators decided to integrate the preclinical courses with the clinical courses by using the systemic-integrating curricular system that dilutes classical disciplines and integrates material based on organ systems, and in 2 studies educators limited reforms to clinical courses only. Eight studies discussed the implementation of a formative evaluation system, 4 studies discussed faculty training, and 15 studies discussed the application of various instructional methods. Other issues that were also addressed include enhancing research, improving patient-doctor communication, developing interpersonal and teamwork skills, cultivating independent lifelong learning habits, and improving problem-solving capabilities. CONCLUSIONS: The medical schools in our study have adopted various comprehensive curricular changes, moving from a knowledge-based to a competency-based model, and from traditional standards to international standards. Many institutions face challenges when implementing curricular reforms, such as what to integrate and how to do so, the unintended omission of important material, ensuring coordination between different organizations and departments, and the training of faculty.

Curriculum reform at Chinese medical schools: what have we learned?

INTRODUCTION: Curriculum reform at Chinese medical schools has attracted a lot of attention recently. Several leading medical schools in China have undergone exploratory reforms and in so doing, have accumulated significant experience and have made considerable progress. METHODS: An analysis of the reforms conducted by 38 Chinese medical colleges that were targeted by the government for upgrade was performed. Drawing from both domestic and international literature, we designed a questionnaire to determine what types of curricular reforms have occurred at these institutions and how they were implemented. Major questions touched upon the purpose of the reforms, curricular patterns, improvements in teaching methods post-reform, changes made to evaluation systems post-reform, intra-university reform assessment, and what difficulties the schools faced when instituting the reforms. Besides the questionnaire, relevant administrators from each medical school were also interviewed to obtain more qualitative data. RESULTS: Out of the 38 included universities, twenty-five have undergone major curricular reforms. Among them, 60.0% adopted an organ system-based curriculum model, 32.0% adopted a problem-based curriculum model, and 8.0% adopted a hybrid curriculum model. About 60.0% of the schools' reforms involved both the "pre-clinical" and the "clinical" curricula, 32.0% of the schools' reforms were limited to the "pre-clinical" curricula, and 8.0% of the schools' reforms only involved the "clinical" curricula. Following curricular reform, 60.0% of medical schools experienced an overall reduction in teaching hours, 76.0% reported an increase in their students' clinical skills, and 60.0% reported an increase in their students' research skills. DISCUSSION: Medical curricular reform is still in its infancy in China. The republic's leading medical schools have engaged in various approaches to bring innovative teaching methods to their respective institutions. However, due to limited resources and the shackle of traditional pedagogical beliefs among many faculty and administrators, progress has been significantly hindered. Despite these and other challenges, many medical schools report positive initial results from the reforms that they have enacted. Although the long term effects of such reforms remain unclear, curricular reform appears to be the inevitable solution to China's growing need for high-quality medical doctors.

A snapshot of the status of problem-based learning (PBL) in Chinese medical schools.

INTRODUCTION: In North America, where it was born, problem-based learning (PBL) has seen dips and rises in its popularity, but its inherent strengths have led to its spread to medical schools all over the world. Although its use at medical schools in some Western countries has already been examined, no one has looked at its status in many other countries, including China. The aim of this study is to determine the number of schools currently using PBL in China, the degree to which they use it, and the reasoning behind such usage. METHODS: We used survey and internet search to examine PBL usage at Chinese medical schools. We were able to collect data from 43 first-class Chinese medical schools that are geographically diverse and thus representative of medical schools all across China. RESULTS: 34 (79.1%) of the 43 medical schools use PBL in the preclinical curriculum. Of the 34, data were collected from 24 (70.6%) medical schools regarding the extent of their PBL usage. Nine (37.5%) schools use PBL for less than 10% of preclinical hours, 14 (58.3%) schools use PBL for 10-50% of preclinical hours, and one (4.2%) school uses PBL for more than 50% of preclinical hours. CONCLUSION: In our sample of Chinese medical institutions, a large majority of schools use PBL, however, most schools use it for less than 50% of total preclinical curricular hours. Our results suggest that schools are interested in increasing the number of curricular hours devoted to PBL but are constrained by resources.

Association between maternal behavior in infancy and adult mental health: a 30-year prospective study.

BACKGROUND: Existing theories suggest that the mother-infant relationship has a potentially significant effect on long-term adult mental health, but there are few empirical data to support this view. Even fewer prior studies have examined the specific dynamics of the mother-infant relationship and their association with adult mental health. METHODS: A total of 1752 inner-city infants born between 1960 and 1965 were followed prospectively as a part of the Collaborative Perinatal Project (CPP) and the Johns Hopkins Pathways to Adulthood Study. Multiple observations of development and an extensive adult interview were performed. Maternal behavior was observed and systematically rated at the infant's 4-month pediatric neurological evaluation and at 8 months by a developmental psychologist. Factor analysis was used to organize the maternal behavior variables into different types of dysfunctional mother-infant relationships. Adult mental health was assessed at the follow-up interview, when the infant had reached the age of 27-33 years, by the General Health Questionnaire (GHQ) and self-perception of current mental health. RESULTS: There was a significant association between unsupportive maternal behavior at 8 months and subsequent poor adult mental health (Fisher's exact test, p=0.026). There was no association between overly involved maternal behavior and poor mental health as an adult. After adjustment for potential confounding variables, the elevated rates of poor adult mental health in children of mothers who exhibited unsupportive maternal behavior at 8 months persisted (OR=1.41 [95% CI=1.00-1.97], p<0.05). CONCLUSION: Infants who experience unsupportive maternal behavior at 8 months have an increased risk for developing psychological sequelae later in life.

Medical education in Ecuador.

BACKGROUND: Ecuador, the smallest of the Andean countries, is located in the northwest portion of South America. The nation's 14.5 million people have a tremendous need for high quality primary care. AIMS: To describe the profound advances as well as the persistent needs in medical education in Ecuador that have occurred with globalization and with the modernization of the country. METHODS: Through an extensive search of the literature; medical school data; reports from the Ecuador Ministry of Public Health and Ministry of Education; and information from the National Secretary of Higher Education, Science, and Innovation (SENESCYT), the medical education system in Ecuador has been thoroughly examined. RESULTS: The National System of Higher Education in Ecuador has experienced significant growth over the last 20 years. As of 2009 the system boasts 19 medical schools, all of which offer the required education needed to obtain the title of Physician, but only 12 of which offer postgraduate clinical training. Of these 19 universities, nine are public, five are private and self-financed, and five are private and co-financed. Post-graduate options for medical students include: (1) Clinical specialization, (2) Higher diploma, (3) Course specialization, (4) Master's degree, and (5) PhD degree. CONCLUSION: The rapid growth of Ecuador's system of medical education has led to inevitable gaps that threaten its ability to sustain itself. Chief among these is the lack of well-trained faculty to supply its medical schools. To ensure an adequate supply of faculty exists, the creation of sufficient postgraduate, sub-specialization, and PhD training positions must be created and maintained.

Integration of responses within and across Arabidopsis natural accessions uncovers loci controlling root systems architecture.

Phenotypic plasticity is presumed to be involved in adaptive change toward species diversification. We thus examined how candidate genes underlying natural variation across populations might also mediate plasticity within an individual. Our implementation of an integrative "plasticity space" approach revealed that the root plasticity of a single Arabidopsis accession exposed to distinct environments broadly recapitulates the natural variation "space." Genome-wide association mapping identified the known gene PHOSPHATE 1 (PHO1) and other genes such as Root System Architecture 1 (RSA1) associated with differences in root allometry, a highly plastic trait capturing the distribution of lateral roots along the primary axis. The response of mutants in the Columbia-0 background suggests their involvement in signaling key modulators of root development including auxin, abscisic acid, and nitrate. Moreover, genotype-by-environment interactions for the PHO1 and RSA1 genes in Columbia-0 phenocopy the root allometry of other natural variants. This finding supports a role for plasticity responses in phenotypic evolution in natural environments.

Suicidal ideation in medical students: who is at risk?

INTRODUCTION: Suicide is one of the most tragic problems medical schools are facing today. It is an issue that has not escaped medical schools in either developing or developed nations. To combat this trend, medical educators require efficient and effective strategies for the immediate identification of students who are at an elevated risk of harming themselves. MATERIALS AND METHODS: National Yang Ming University medical students were surveyed on various demographic, academic, personal, and extracurricular subjects as well as assessed for suicidal ideation. In addition, students completed the Chinese Health Questionnaire (CHQ, a translated and modified version of the General Health Questionnaire, GHQ), and the Taiwanese Depression Questionnaire (TDQ, a translated and modified version of the Center for Epidemiologic Studies' Depression Scale, CES-D). RESULTS: The rate of suicidal ideation was significantly higher in second year students as opposed to fi rst year students (P <0.01). Students of lower socioeconomic status (P = 0.04), with non-inflammatory joint pain (P = 0.02), with headache (P = 0.047), with sleep disorders (P = 0.04), who scored as depressed on the TDQ (P <0.01), and/or who scored abnormally on the CHQ (P <0.01) were all significantly more likely to have experienced suicidal ideation. CONCLUSION: A number of groups at high risk for suicidal ideation, and thus in greater need of support, were identified. Suicide intervention programmes and depression counselling should target older students and students of lower socioeconomic status. Students presenting to university clinics with non-inflammatory joint pain, headache, and/or sleep disorders should be evaluated for suicidal tendencies. The TDQ and CHQ are potentially valuable screening tests for early detection of potential suicidal students.

Characterization of the neuropsychological phenotype of glycine N-methyltransferase-/- mice and evaluation of its responses to clozapine and sarcosine treatments.

Glycine N-methyltransferase (GNMT) affects cellular methylation capacity through regulating the ratio between S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). The product of its enzymatic reaction-sarcosine has antipsychotic effect in patients with schizophrenia. In this study, through RT-PCR and immunohistochemical staining, we demonstrated that GNMT expressed in various neurons located in the cerebral cortex, hippocampus, substantia nigra and cerebellum. Compared to the wild-type mice, Gnmt-/- mice had significantly lower level of sarcosine in the cerebral cortex. Real-time PCR identified genes involved in the methionine metabolism (Dnmt1 and Dnmt3a), ErbB (Nrg1 and ErbB4) and mTOR (Akt2, S6, S6k1 and S6k2) signaling pathways were dysregulated significantly in the cortex of Gnmt-/- mice. Acoustic startle reflex test demonstrated that Gnmt-/- mice had significantly lower level of prepulse inhibition and the deficit was ameliorated through clozapine or sarcosine treatment. Furthermore, liver-specific-human-GNMT transgenic with Gnmt-/- (Tg-GNMT/Gnmt-/-) mice were used to rule out that the phenotype was due to abnormal liver function. In summary, the neuropsychological abnormalities found in Gnmt-/- mice may represent an endophenotype of schizophrenia. GNMT plays an important role in maintaining normal physiological function of brain and Tg-GNMT/Gnmt-/- mice are useful models for development of therapeutics for patients with schizophrenia.

Quality of life and needs assessment on people living with HIV and AIDS in Malawi.

PURPOSE: Malawi is a sub-Saharan African nation with a severe HIV epidemic. The quality of life (QoL) has never been investigated among people living with HIV and AIDS (PLWHA) in Malawi. This study examines the QoL and associated factors including life needs among PLWHA at different stages of their illness in the northern region of Malawi. METHODS: Survey analysis of consecutive outpatient participants receiving highly active antiretroviral therapy at the Rainbow Clinic and non-HIV patients receiving care at the affiliated Mzuzu Central Hospital during a one-month period was performed. Laboratory testing and clinical diagnosis were used to determine HIV status, determine CD4 count, and classify WHO clinical stage. A total of 267 HIV-infected patients and 598 non-HIV participants completed a needs assessment and a Short Form-36 (SF-36) questionnaire, which contained a QoL subscale. SF-36 subscales and needs assessment scores were analyzed using t-test, ANOVA test, and Generalized Linear Model-Tukey's test. RESULTS: HIV-positive patients had significantly lower physical functioning (p=0.0365), mental health (p=0.001), social functioning (p<0.0001), and mental component summary (p=0.0069) scores than HIV-negative patients. Further, WHO Stage III HIV patients had significantly lower vitality (p=0.0439) and mental health (p=0.0022) scores than WHO Stages I and II patients; and WHO Stage IV patients had significantly lower vitality (p=0.0015), mental health (p=0.0006), and physical component summary (p=0.0443) scores than WHO Stages I and II patients. Finally, AIDS patients, as determined by CD4 count, had significantly lower bodily pain (p=0.0423) and physical component summary (p=0.0148) scores than non-AIDS, HIV-positive patients. CONCLUSION: HIV patients undergoing treatment in Malawi have a significantly lower QoL, both mentally and physically, than their non-HIV counterparts. Further, HIV patients at more advanced stages, both by the WHO definition and by CD4 count, have a significantly lower QoL than HIV patients at earlier stages of the disease.