Erratum: Scaling up the task-sharing of psychological therapies: A formative study of the PEERS smartphone application for supervision and quality assurance in rural India - CORRIGENDUM.

[This corrects the article DOI: 10.1017/gmh.2024.11.].

Scaling up the task-sharing of psychological therapies: A formative study of the PEERS smartphone application for supervision and quality assurance in rural India.

Measurement-based peer supervision is one strategy to assure the quality of psychological treatments delivered by non-mental health specialist providers. In this formative study, we aimed to 1) describe the development and 2) examine the acceptability and feasibility of PEERS (Promoting Effective mental healthcare through peER Supervision)-a novel smartphone app that aims to facilitate registering and scheduling patients, collecting patient outcomes, rating therapy quality and assessing supervision quality-among frontline treatment providers delivering behavioral activation treatment for depression. The PEERS prototype was developed and tested in 2021, and version 1 was launched in 2022. To date, 215 treatment providers (98% female; ages 30-35) in Madhya Pradesh and Goa, India, have been trained to use PEERS and 65.58% have completed the supplemental, virtual PEERS course. Focus group discussions with 98 providers were examined according to four themes-training and education, app effectiveness, user experience and adherence and data privacy and safety. This yielded commonly endorsed facilitators (e.g., collaborative learning through group supervision, the convenience of consolidated patient data), barriers (e.g., difficulties with new technologies) and suggested changes (e.g., esthetic improvements, suicide risk assessment prompt). The PEERS app has the potential to scale measurement-based peer supervision to facilitate quality assurance of psychological treatments across contexts.

In Silico Analysis of Natural Plant-Derived Cyclotides with Antifungal Activity against Pathogenic Fungi.

BACKGROUND: Fungal infections in plants, animals, and humans are widespread across the world. Limited classes of antifungal drugs to treat fungal infections and loss of drug efficacy due to rapidly evolving fungal strains pose a challenge in the agriculture and health sectors. Hence, the search for a new class of antifungal agents is imperative. Cyclotides are cyclic plant peptides with multiple bioactivities, including antifungal activity. They have six conserved cysteine residues forming three disulfide linkages (CI-CIV, CII-CV, CIII-CVI) that establish a Cyclic Cystine Knot (CCK) structure, making them extremely resistant to chemical, enzymatic, and thermal attacks. AIM: This in silico analysis of natural, plant-derived cyclotides aimed to assess the parameters that can assist and hasten the process of selecting the cyclotides with potent antifungal activity and prioritize them for in vivo/ in vitro experiments. OBJECTIVE: The objective of this study was to conduct in silico studies to compare the physicochemical parameters, sequence diversity, surface structures, and membrane-cyclotide interactions of experimentally screened (from literature survey) potent (MIC ≤ 20 µM) and non-potent (MIC > 20 µM) cyclotides for antifungal activity. METHODOLOGY: Cyclotide sequences assessed for antifungal activity were retrieved from the database (Cybase). Various online and offline tools were used for sequence-based studies, such as physicochemical parameters, sequence diversity, and neighbor-joining trees. Structure-based studies involving surface structure analysis and membrane-cyclotide interaction were also carried out. All investigations were conducted in silico. RESULTS: Physicochemical parameter values, viz. isoelectric point, net charge, and the number of basic amino acids, were significantly higher in potent cyclotides compared to non-potent cyclotides. The surface structure of potent cyclotides showed a larger hydrophobic patch with a higher number of hydrophobic amino acids. Furthermore, the membrane-cyclotide interaction studies of potent cyclotides revealed lower transfer free energy (ΔG transfer) and higher penetration depth into fungal membranes, indicating higher binding stability and membrane-disruption ability. CONCLUSION: These in silico studies can be applied for rapidly identifying putatively potent antifungal cyclotides for in vivo and in vitro experiments, which will ultimately be relevant in the agriculture and pharmaceutical sectors.

CD146 as a prognostic marker in breast cancer: A meta-analysis.

BACKGROUND: CD146, a cell adhesion molecule, was first discovered in melanoma. Since then, it has been established as a promoter of tumor progression and metastasis. Many recent clinical studies have associated CD146 overexpression with poor prognosis in various cancers. However, clinical relevance of CD146 in prognosis of breast cancer has been poorly studied. METHODS: We performed meta-analysis of data of all clinical studies associated with the prognostic value of CD146 expression in breast cancer. Relevant studies were retrieved from PubMed database as per the inclusion and exclusion criteria, data were extracted independently and carefully by two reviewers with the help of standardized form, and meta-analysis was performed to correlate CD146 expression with molecular subtypes, lymph node metastasis, and overall survival in breast cancer. RESULTS: Our findings suggest that CD146 expression is predominantly found in triple-negative breast cancer subtype (pooled odds ratio = 2.98, 95% confidence interval [CI] =2.19-4.05, P < .00001) and breast tumors overexpressing CD146 have a higher risk of lymph node metastasis (pooled relative risk = 1.64, 95% CI = 1.44-1.87, P < .00001). Furthermore, high expression of CD146 was associated with poor prognosis in breast cancer (pooled hazard ratio = 1.51, 95% CI = 1.21-1.87, P = .0002). CONCLUSION: Overall results suggested that CD146 may be a potential prognostic marker to predict metastatic potential and disease outcomes in breast cancer and can be used as a therapeutic target.

Dyschromatopsia and contrast sensitivity changes in COVID-19 patients.

PURPOSE: To evaluate the alterations in the psycho-physical tests, contrast sensitivity (CS) and hue discrimination (total estimation score, TES) in COVID-19 patients. METHODS: A prospective case-control study was undertaken in 2021-22 to look at CS and TES among COVID-19 patients and RT-PCR negative normal subjects by a mobile app "smart optometry" and X-Rite's free online version of Farnsworth-Munsell 100 hue test. Strict visual acuity (minimum of 6/9 equivalent on Snellen) and other clinical parameters were used as exclusion criteria to filter potentially confounding pre-receptoral co-morbid conditions. The effect of mismatch in recruiting age and sex matched controls during the pandemic were analyzed by multivariate linear regression. RESULT: One-way ANOVA ruled out any influence of gender on CS and TES; however, there was significant difference in the TES on Mann Whitney U test (TES- 2.95 +/- 3.8 for cases; 0.30 +/- 1.1 for controls; p <0.001) and it persisted after accounting for age. Six controls with breakthrough infections had a significant deterioration in TES (Mean scores -3.0; 95% CI = -5.89 to -0.11; p = 0.04) on paired t test. Qualitative analysis showed that S-cone mediated deficiencies outnumber those affecting M-L cone mediated deficiencies. Among 53 subjects exhibiting three sensory features, anosmia, loss of taste and dyschromatopsia, nine (16.98%) had all features concurrently. CONCLUSION: The study demonstrates that COVID-19 infection leads to altered TES representing dyschromatopsia -an ocular counterpart of anosmia, with little difference on CS.

Fluorophore position of headgroup-labeled Gb3 glycosphingolipids in lipid bilayers.

Fluorescent lipid probes are an invaluable tool for investigating lipid membranes. In particular, localizing certain receptor lipids such as glycosphingolipids within phase-separated membranes is of pivotal interest to understanding the influence of protein-receptor lipid binding on membrane organization. However, fluorescent labeling can readily alter the phase behavior of a lipid membrane because of the interaction of the fluorescent moiety with the membrane interface. Here, we investigated Gb3 glycosphingolipids, serving as receptor lipids for the protein Shiga toxin, with a headgroup attached BODIPY fluorophore separated by a polyethylene glycol (PEG) spacer of different lengths. We found that the diffusion coefficients of the fluorescently labeled Gb3 species in 1,2-dioleoyl-sn-glycero-3-phosphocholine/Gb3 (98:2, n/n) supported lipid bilayers are unaltered by the PEG spacer length. However, quenching as well as graphene-induced energy transfer experiments indicated that the length of the PEG spacer (n = 3 and n = 13) alters the position of the BODIPY fluorophore. In particular, the graphene-induced energy transfer technique provided accurate end-to-end distances between the fluorophores in the two leaflets of the bilayer thus enabling us to quantify the distance between the membrane interface and the fluorophore with sub-nanometer resolution. The spacer with three oligo ethylene glycol groups positioned the BODIPY fluorophore directly at the membrane interface favoring its interaction with the bilayer and thus may disturb lipid packing. However, the longer PEG spacer (n = 13) separated the BODIPY moiety from the membrane surface by 1.5 nm.

Metagenome-Assembled Genomes from Photo-Oxidized and Nonoxidized Oil-Degrading Marine Microcosms.

We performed deep metagenomic sequencing on hydrocarbon-degrading marine microcosms designed to experimentally determine the effect of photo-oxidation on oil biodegradation dynamics. Assembly, binning, and dereplication yielded 73 unique metagenome-assembled genomes (MAGs) from 6 phyla, of which 61 are predicted to be over 90% complete.

Soluble CD146 as a Potential Target for Preventing Triple Negative Breast Cancer MDA-MB-231 Cell Growth and Dissemination.

Background: Triple Negative Breast Cancers (TNBC) are the most aggressive breast cancers and lead to poor prognoses. This is due to a high resistance to therapies, mainly because of the presence of Cancer Stem Cells (CSCs). Plasticity, a feature of CSCs, is acquired through the Epithelial to Mesenchymal Transition (EMT), a process that has been recently shown to be regulated by a key molecule, CD146. Of interest, CD146 is over-expressed in TNBC. Methods: The MDA-MB-231 TNBC cell line was used as a model to study the role of CD146 and its secreted soluble form (sCD146) in the development and dissemination of TNBC using in vitro and in vivo studies. Results: High expression of CD146 in a majority of MDA-MB-231 cells leads to an increased secretion of sCD146 that up-regulates the expression of EMT and CSC markers on the cells. These effects can be blocked with a specific anti-sCD146 antibody, M2J-1 mAb. M2J-1 mAb was able to reduce tumour development and dissemination in a model of cells xenografted in nude mice and an experimental model of metastasis, respectively, in part through its effects on CSC. Conclusion: We propose that M2J-1 mAb could be used as an additional therapeutic approach to fight TNBC.

Angiogenesis induction in breast cancer: A paracrine paradigm.

Breast cancer is the most prevalent type of cancer among women globally. Angiogenesis contributes significantly to breast cancer progression and dissemination. Neovascularization is concurrent with the progression and growth of breast cancer. Breast cancer cells control angiogenesis by secreting pro-angiogenic factors like fibroblast growth factor, vascular endothelial growth factor, interleukin, transforming growth factor-ß, platelet-derived growth factor and several others. These pro-angiogenic factors trigger neovascularization, and thereby lead to breast cancer development and metastasis. The hypoxia-inducible factor (HIF)-regulated angiogenesis cascade is a crucial underlying factor in breast cancer growth and metastasis. To that end, several efforts have been made to identify druggable targets within the HIF-angiogenesis components. However, escape pathways are a major hindrance for targeted therapies against angiogenesis. Thus, understanding the key factors that trigger breast cancer angiogenesis is critical in elucidating ways to inhibit breast cancer. The current review provides an overview of the key growth factors that trigger breast cancer angiogenesis.

The Role of the Adhesion Receptor CD146 and Its Soluble Form in Human Embryo Implantation and Pregnancy.

CD146 is an adhesion molecule essentially located in the vascular system, which has been described to play an important role in angiogenesis. A soluble form of CD146, called sCD146, is detected in the bloodstream and is known as an angiogenic factor. During placental development, CD146 is selectively expressed in extravillous trophoblasts. A growing body of evidence shows that CD146 and, in particular, sCD146, regulate extravillous trophoblasts migration and invasion both in vitro and in vivo. Hereby, we review expression and functions of CD146/sCD146 in the obstetrical field, mainly in pregnancy and in embryo implantation. We emphasized the relevance of quantifying sCD146 in the plasma of pregnant women or in embryo supernatant in the case of in vitro fertilization (IVF) to predict pathological pregnancy such as preeclampsia or implantation defect. This review will also shed light on some major results that led us to define CD146/sCD146 as a biomarker of placental development and paves the way toward identification of new therapeutic targets during implantation and pregnancy.

Transmembrane ß-peptide helices as molecular rulers at the membrane surface.

ß-Peptides are known to form 14-helices with high conformational rigidity, helical persistence length, and well-defined spacing and orientation regularity of amino acid side chains. Therefore, ß-peptides are well suited to serve as backbone structures for molecular rulers. On the one hand, they can be functionalized in a site-specific manner with molecular probes or fluorophores, and on the other hand, the ß-peptide helices can be recognized and anchored in a biological environment of interest. In this study, the ß-peptide helices were anchored in lipid bilayer membranes, and the helices were elongated in the outer membrane environment. The distances of the covalently bound probes to the membrane surface were determined using graphene-induced energy transfer (GIET) spectroscopy, a method based on the distance-dependent quenching of a fluorescent molecule by a nearby single graphene sheet. As a proof of principle, the predicted distances were determined for two fluorophores bound to the membrane-anchored ß-peptide molecular ruler.

USMLE Step 2 CK: Best Predictor of Multimodal Performance in an Internal Medicine Residency.

BACKGROUND: Internal medicine (IM) residency programs receive information about applicants via academic transcripts, but studies demonstrate wide variability in satisfaction with and usefulness of this information. In addition, many studies compare application materials to only 1 or 2 assessment metrics, usually standardized test scores and work-based observational faculty assessments. OBJECTIVE: We sought to determine which application materials best predict performance across a broad array of residency assessment outcomes generated by standardized testing and a yearlong IM residency ambulatory long block. METHODS: In 2019, we analyzed available Electronic Residency Application Service data for 167 categorical IM residents, including advanced degree status, research experience, failures during medical school, undergraduate medical education award status, and United States Medical Licensing Examination (USMLE) scores. We compared these with post-match residency multimodal performance, including standardized test scores and faculty member, peer, allied health professional, and patient-level assessment measures. RESULTS: In multivariate analyses, USMLE Step 2 Clinical Knowledge (CK) scores were most predictive of performance across all residency performance domains measured. Having an advanced degree was associated with higher patient-level assessments (eg, physician listens, physician explains, etc). USMLE Step 1 scores were associated with in-training examination scores only. None of the other measured application materials predicted performance. CONCLUSIONS: USMLE Step 2 CK scores were the highest predictors of residency performance across a broad array of performance measurements generated by standardized testing and an IM residency ambulatory long block.

Small molecular organic nanocrystals resemble carbon nanodots in terms of their properties.

The most commonly observed phenomena in carbon nanodots (CNDs) are the strong excitation wavelength dependent multicolor fluorescence emission and the particle size distribution between 3-5 nm observed using a transmission electron microscope (TEM). However, it is not evident yet whether the emission originates from the particles observed using a TEM. In this article, we show that hydrothermal treatment of citric acid produces methylenesuccinic acid, which gives rise to hydrogen-bonded nano-assemblies with CND-like properties. While single crystal X-ray crystallography confirms the structure of methylenesuccinic acid, fluorescence correlation spectroscopy (FCS) confirms the presence of a molecular fluorophore with an average hydrodynamic diameter of ∼0.9 nm. This size is much smaller than the size of the particles observed using a TEM. We conclude that the particles observed using a TEM are the drying mediated nanocrystals of methylenesuccinic acid.

Cellular Components, Including Stem-Like Cells, of Preterm Mother's Mature Milk as Compared with Those in Her Colostrum: A Pilot Study.

PARTICIPATING AND STUDY OBJECTIVE: Whether the preterm mothers' mature milk retains the same cellular components as those in colostrum including stem-like cell, cell adhesion molecules, and immune cells. PARTICIPANTS: A total of five preterm mothers were recruited for the study having an average age of 30.2 years and gestational age of 29.8 weeks from the Pristine Women's Hospital, Kolhapur. Colostrum milk was collected within 2-5 days and matured milk was collected 20-30 days after delivery from the same mothers. METHODOLOGY: Integral cellular components of 22 markers including stem cells, immune cells, and cell adhesion molecules were measured using flowcytometry. OUTCOME: Preterm mature milk was found to possess higher expressions of hematopoietic stem cells, mesenchymal stem-like cells, immune cells, few cell adhesion molecules, and side population cells than colostrum. CONCLUSION: The increased level of these different cell components in mature milk may be important in the long-term preterm baby's health growth. Further similar research in a larger population of various gestational ages and lactation stages of preterm mothers is warranted to support these pilot findings.