Phenotypic clusters of type 2 diabetes mellitus among North Indians reveal higher levels of insulin deficiency along with insulin resistance.

BACKGROUND: Type 2 diabetes is now considered a heterogenous disease. Distinct clusters have been identified with patterns varying between Europeans and South Asians as well as between South Indians who have described a novel cluster; Combined Insulin-Resistant and Deficient Diabetes, and individuals from West and East India who have reported that insulin deficiency is the primary driver of heterogeneity. Therefore, North Indian patients may also have a distinct, novel clustering pattern due to unique genetic, epigenetic, and environmental factors. We aim to identify clusters of type 2 diabetes in North Indians and to describe the different characteristics of these clusters. METHODS: The K value for the optimal number of clusters was obtained from two-step clustering. K means clustering was done with this K value using SPSS 29.0 software. Variables used for clustering were age, BMI, HbA1c, HOMA-beta, HOMA-IR, and waist circumference. RESULTS: Four phenotypically different clusters were identified in 469 individuals with type 2 diabetes. Cluster 1 was severe insulin deficient diabetes (15%), Cluster 2 was severe insulin resistant diabetes (22%), Cluster 3 was moderate obesity-related diabetes (35%), and Cluster 4 was moderate age-related diabetes (27%). Clusters 1 and 2 were similar to earlier studies but in different proportions. Clusters 3 and 4 characteristics were different from earlier studies, with greater impairment in beta cell function and higher HbA1c levels. Significant insulin resistance was noted in all clusters. CONCLUSION: The phenotypic clusters of type 2 diabetes identified in the present study were characterized by high levels of insulin deficiency along with important contributions from insulin resistance.

mtx-COBRA: Subcellular localization prediction for bacterial proteins.

BACKGROUND: Bacteria can have beneficial effects on our health and environment; however, many are responsible for serious infectious diseases, warranting the need for vaccines against such pathogens. Bioinformatic and experimental technologies are crucial for the development of vaccines. The vaccine design pipeline requires identification of bacteria-specific antigens that can be recognized and can induce a response by the immune system upon infection. Immune system recognition is influenced by the location of a protein. Methods have been developed to determine the subcellular localization (SCL) of proteins in prokaryotes and eukaryotes. Bioinformatic tools such as PSORTb can be employed to determine SCL of proteins, which would be tedious to perform experimentally. Unfortunately, PSORTb often predicts many proteins as having an "Unknown" SCL, reducing the number of antigens to evaluate as potential vaccine targets. METHOD: We present a new pipeline called subCellular lOcalization prediction for BacteRiAl Proteins (mtx-COBRA). mtx-COBRA uses Meta's protein language model, Evolutionary Scale Modeling, combined with an Extreme Gradient Boosting machine learning model to identify SCL of bacterial proteins based on amino acid sequence. This pipeline is trained on a curated dataset that combines data from UniProt and the publicly available ePSORTdb dataset. RESULTS: Using benchmarking analyses, nested 5-fold cross-validation, and leave-one-pathogen-out methods, followed by testing on the held-out dataset, we show that our pipeline predicts the SCL of bacterial proteins more accurately than PSORTb. CONCLUSIONS: mtx-COBRA provides an accessible pipeline that can more efficiently classify bacterial proteins with currently "Unknown" SCLs than existing bioinformatic and experimental methods.

Establishing the validity of a diagnostic questionnaire for childbirth-related posttraumatic stress disorder.

BACKGROUND: Labor and delivery can entail complications and severe maternal morbidities that threaten a woman's life or cause her to believe that her life is in danger. Women with these experiences are at risk for developing posttraumatic stress disorder. Postpartum posttraumatic stress disorder, or childbirth-related posttraumatic stress disorder, can become an enduring and debilitating condition. At present, validated tools for a rapid and efficient screen for childbirth-related posttraumatic stress disorder are lacking. OBJECTIVE: We examined the diagnostic validity of the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, for detecting posttraumatic stress disorder among women who have had a traumatic childbirth. This Checklist assesses the 20 Diagnostic and Statistical Manual of Mental Disorders, posttraumatic stress disorder symptoms and is a commonly used patient-administrated screening instrument. Its diagnostic accuracy for detecting childbirth-related posttraumatic stress disorder is unknown. STUDY DESIGN: The sample included 59 patients who reported a traumatic childbirth experience determined in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, posttraumatic stress disorder criterion A for exposure involving a threat or potential threat to the life of the mother or infant, experienced or perceived, or physical injury. The majority (66%) of the participants were less than 1 year postpartum (for full sample: median, 4.67 months; mean, 1.5 years) and were recruited via the Mass General Brigham's online platform, during the postpartum unit hospitalization or after discharge. Patients were instructed to complete the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, concerning posttraumatic stress disorder symptoms related to childbirth. Other comorbid conditions (ie, depression and anxiety) were also assessed. They also underwent a clinician interview for posttraumatic stress disorder using the gold-standard Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. A second administration of the checklist was performed in a subgroup (n=43), altogether allowing an assessment of internal consistency, test-retest reliability, and convergent and diagnostic validity of the Checklist. The diagnostic accuracy of the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, in reference to the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, was determined using the area under the receiver operating characteristic curve; an optimal cutoff score was identified using the Youden's J index. RESULTS: One-third of the sample (35.59%) met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for a posttraumatic stress disorder diagnosis stemming from childbirth. The Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, symptom severity score was strongly correlated with the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, total score (ρ=0.82; P<.001). The area under the receiver operating characteristic curve was 0.93 (95% confidence interval, 0.87-0.99), indicating excellent diagnostic performance of the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. A cutoff value of 28 maximized the sensitivity (0.81) and specificity (0.90) and correctly diagnosed 86% of women. A higher value (32) identified individuals with more severe posttraumatic stress disorder symptoms (specificity, 0.95), but with lower sensitivity (0.62). Checklist scores were also stable over time (intraclass correlation coefficient, 0.73), indicating good test-retest reliability. Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, scores were moderately correlated with the depression and anxiety symptom scores (Edinburgh Postnatal Depression Scale: ρ=0.58; P<.001 and the Brief Symptom Inventory, anxiety subscale: ρ=0.51; P<.001). CONCLUSION: This study demonstrates the validity of the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, as a screening tool for posttraumatic stress disorder among women who had a traumatic childbirth experience. The instrument may facilitate screening for childbirth-related posttraumatic stress disorder on a large scale and help identify women who might benefit from further diagnostics and services. Replication of the findings in larger, postpartum samples is needed.

Assessment of understanding about human papilloma virus vaccination among undergraduate medical students in a developing country: Perspective from India.

BACKGROUND AND AIMS: Human papilloma virus (HPV) infection is the most common sexually transmitted infection responsible for cervical cancer in women. There is no cure for HPV but safe and effective vaccinations before sexual debut can definitely decrease the incidence of cervical cancer. This research aims to explore the basic understanding of medical students about cervical cancer, HPV and HPV vaccination. METHODS AND MATERIAL: This was a descriptive, questionnaire based cross-sectional study conducted among the undergraduate medical students of All India Institute of Medical Sciences, Jodhpur from April 2018 to May 2018. A total of 238 respondents participated in the study. For statistical analysis, 'Z' score was used for categorical data and student t test was used for normally distributed continuous data. RESULTS: Overall, 41% students had good knowledge about HPV infection and HPV vaccination while 44% students had average knowledge and 15% had poor knowledge. The majority of them (>80%) knew that HPV is responsible for cervical cancer and ano-genital warts but their awareness was not of the same order when it came to associating HPV with penile and oropharyngeal cancer (60%). Females had better knowledge as compared to males and this difference was statistically significant (P < 0.05). 88% of the students were willing to accept the vaccination while only 10% of females were previously vaccinated. CONCLUSION: Medical students, who are potential recipients of the HPV vaccine themselves, can play a unique role in promoting awareness about HPV vaccination in the future.