Psychometric Properties of the Arabic Version of the Problem Areas in Diabetes Scale in Primary Care

BackgroundThe Problem Areas in Diabetes (PAID) scale is a reliable and valid tool that is widely used for diabetes-distress screening, but the Arabic version of the scale lacks validity and reliability analysis in primary healthcare (PHC) patients. Our study aimed to evaluate the psychometric properties of the Arabic version of the PAID (AR-PAID) scale among Egyptian patients with type 2 diabetes mellitus (T2DM) in PHC settings.MethodsWe conducted a cross-sectional study on a convenience sample of 200 patients from six rural PHC settings in the Ismailia governorate. The confirmatory factor analysis (CFA) was performed to test the goodness-of-fit to the predefined models of the PAID. Convergent construct was evaluated through correlations with the Arabic versions of the Patient Health Questionnaire 9 (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and 5-item World Health Organization Well-Being Index (WHO-5), additionally glycated hemoglobin (HbA1c) levels. Discriminant validity was evaluated through associations with patients' sociodemographic and clinical characteristics. Reliability was evaluated through internal consistency (Cronbach's α) and test-retest reliability analysis (intraclass correlation coefficient, ICC).ResultsThe CFA demonstrated the best fit for a four-factor model. The AR-PAID was significantly correlated with the following measures: PHQ-9 (rho = 0.71, p < 0.001), GAD-7 (rho = 0.50, p < 0.001), WHO-5 (rho = −0.69, p < 0.001), and HbA1c (rho = 0.36, p < 0.001), supporting sound convergent validity. Discriminant validity was satisfactory demonstrated. Internal consistency was excellent (α = 0.96) and test-retest reliability was stable (ICC = 0.97).ConclusionsThe AR-PAID scale is a valid and reliable instrument for diabetes-distress screening in primary care patients with T2DM that can be used in clinical settings and research. Further research is needed to validate short forms of the AR-PAID scale

Menstrual changes after COVID-19 vaccination and/or SARS-CoV-2 infection and their demographic, mood, and lifestyle determinants in Arab women of childbearing age, 2021

BackgroundBy September 2, 2021, over 30,000 COVID-19-vaccinated females had reported menstrual changes to the MHRA's Yellow Card surveillance system. As a result, the National Institutes of Health (NIH) is urging researchers to investigate the COVID-19 vaccine's effects on menstruation. Therefore, this study was conducted to explore the menstrual changes after COVID-19 vaccination and/or SARS-CoV-2 infection and their interrelations with demographic, mood, and lifestyle factors in Arab women of childbearing age (CBA).MethodologyA cross-sectional study was conducted during October 2021 using an Arabic validated and self-administrated questionnaire. In total, 1,254 Women of CBA in the Arabic Population (15–50 y) with regular menstrual cycles were randomly selected from five countries (Saudi Arabia, Egypt, Syria, Libya, and Sudan).ResultsThe mean (SD) age of the 1,254 studied females was 29.6 (8.5) years old. In total, 634 (50%) were married, 1,104 (88.0%) had a University education or above, 1,064 (84.4%) lived in urban areas, and 573 (45.7%) had normal body weight. Moreover, 524 (41.8%) were COVID-19 cases and 98 women (18.7%) reported menstrual changes (MCs). The 1,044 (83.5%) vaccinated females reported 418 (38.5%) MCs after being vaccinated, and these MCs resolved in 194 women (55.1%) after more than 9 months. Statistically significant relationships were observed between the reported MCs and the following variables: age, marital status, level of education, nationality, residence, and BMI. MCs were reported at 293(80.6) after the 2nd dose, and were mainly reported after 482 (46.1) Pfizer, 254 (24.3) Astrazenica, and 92 (8.8) Senopharm.ConclusionMCs among women of CBA after COVID-19 infection and vaccination are prevalent and complex problems, and had many determinates

Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype

Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared with those <16 (P = 0.0095), even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or electrocardiogram-to-electrocardiogram, changes were noted, suggesting the prevalence of abnormalities was underestimated. Electrocardiogram changes occurred independently of seizures or plegic episodes. Electrocardiogram abnormalities are common in alternating hemiplegia, have characteristics reflecting those of inherited cardiac channelopathies and most likely amount to impaired repolarization reserve. The dynamic electrocardiogram and neurological features point to periodic systemic decompensation in ATP1A3-expressing organs. Cardiac dysfunction may account for some of the unexplained premature mortality of alternating hemiplegia. Systematic cardiac investigation is warranted in alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and mortality are potentially preventable

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised