Impact of the COVID-19 pandemic on the mental health of transgender persons in India: Findings from an exploratory qualitative study.

Introduction: Transgender persons in India, who are one of the most vulnerable groups, were particularly impacted by the COVID-19 pandemic. Increased risk of COVID-19, challenges with continuing livelihood, uncertainty, and anxiety around the pandemic over pre-existing social discrimination and exclusion pose risk of a mental health impact as well. To investigate this further, this component of a larger study on experiences in healthcare of transgender persons in India during COVID-19 and looks into the question "How did the COVID-19 pandemic impact the mental health of transgender persons in India". Methods: 22 In-depth interviews (IDI) and 6 focus group discussions (FGD) were conducted virtually and in-person with persons self-identifying as transgender or belonging to ethnocultural transgender communities from different parts of India. Community based participatory research approach was used by ensuring representation from the community in the research team and through a series of consultative workshops. Purposive sampling with snowballing was used. The IDIs and FGDs were recorded, transcribed verbatim and analyzed using an inductive thematic analysis. Results: Mental health of transgender persons were affected in the following ways. Firstly, COVID-19, its associated fear and suffering combined with pre-existing inaccessibility of healthcare and reduced access to mental health care affected their mental health. Secondly, unique social support needs of transgender persons were disrupted by pandemic linked restrictions. Thirdly, pre-existing vulnerabilities such as precarious employment and underlying stigma were exacerbated. Finally, gender dysphoria was a key mediating factor in the impact of COVID-19 on mental health with a negative and positive impact. Conclusions: The study reiterates the need to make systemic changes to make mental healthcare and general healthcare services trans-inclusive while also recognizing the essential nature of gender affirmative services and the need to continue them even during emergencies and disaster situations. While this brings out how public health emergencies can exacerbate vulnerabilities, it also shows how the lived mental health experience of transgender person is intricately linked to the way work, travel and housing is structured in our society and therefore points to the structural nature of the linkage between mental health and gender.

A Case of Idiopathic Retinitis Vasculitis Aneurysms and Neuroretinitis (IRVAN) Treated with Adalimumab.

PURPOSE: To report a case of IRVAN in a 13-year-old girl responding well to Adalimumab and Azathioprine. RESULTS: A 13-year-old girl presented to us with central scotoma for a duration of 10 months. She was treated earlier with oral steroids with poor response. Fundus examination revealed features of IRVAN. She was treated with intravitreal dexamethasone implant in both eyes with oral Mycophenolate Mofetil (MMF) with transient response to it. So she was switched over to subcutaneous Adalimumab 40 mg once in 2 weeks and oral Azathioprine 50 mg BD. The disease activity was well controlled with the current regime. CONCLUSION: Though various treatment modalities have been described in literature for the treatment of IRVAN. This is the first case of IRVAN to be treated with Adalimumab along with Azathioprine to be reported.

Deep Learning to Predict Mortality After Cardiothoracic Surgery Using Preoperative Chest Radiographs.

BACKGROUND: The Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) estimates mortality risk only for certain common procedures (eg, coronary artery bypass or valve surgery) and is cumbersome, requiring greater than 60 inputs. We hypothesized that deep learning can estimate postoperative mortality risk based on a preoperative chest radiograph for cardiac surgeries in which STS-PROM scores were available (STS index procedures) or unavailable (non-STS index procedures). METHODS: We developed a deep learning model (CXR-CTSurgery) to predict postoperative mortality based on preoperative chest radiographs in 9283 patients at Massachusetts General Hospital (MGH) having cardiac surgery before April 8, 2014. CXR-CTSurgery was tested on 3615 different MGH patients and externally tested on 2840 patients from Brigham and Women's Hospital (BWH) having surgery after April 8, 2014. Discrimination for mortality was compared with the STS-PROM using the C-statistic. Calibration was assessed using the observed-to-expected ratio (O/E ratio). RESULTS: For STS index procedures, CXR-CTSurgery had a C-statistic similar to STS-PROM at MGH (CXR-CTSurgery: 0.83 vs STS-PROM: 0.88; P = .20) and BWH (0.74 vs 0.80; P = .14) testing cohorts. The CXR-CTSurgery C-statistic for non-STS index procedures was similar to STS index procedures in the MGH (0.87 vs 0.83) and BWH (0.73 vs 0.74) testing cohorts. For STS index procedures, CXR-CTSurgery had better calibration than the STS-PROM in the MGH (O/E ratio: 0.74 vs 0.52) and BWH (O/E ratio: 0.91 vs 0.73) testing cohorts. CONCLUSIONS: CXR-CTSurgery predicts postoperative mortality based on a preoperative CXR with similar discrimination and better calibration than the STS-PROM. This may be useful when the STS-PROM cannot be calculated or for non-STS index procedures.

Repression of the iron exporter ferroportin may contribute to hepatocyte iron overload in individuals with type 2 diabetes.

OBJECTIVE: Hyperferremia and hyperferritinemia are observed in patients and disease models of type 2 diabetes mellitus (T2DM). Likewise, patients with genetic iron overload diseases develop diabetes, suggesting a tight link between iron metabolism and diabetes. The liver controls systemic iron homeostasis and is a central organ for T2DM. Here, we investigate how the control of iron metabolism in hepatocytes is affected by T2DM. METHODS: Perls Prussian blue staining was applied to analyze iron distribution in liver biopsies of T2DM patients. To identify molecular mechanisms underlying hepatocyte iron accumulation we established cellular models of insulin resistance by treatment with palmitate and insulin. RESULTS: We show that a subset of T2DM patients accumulates iron in hepatocytes, a finding mirrored in a hepatocyte model of insulin resistance. Iron accumulation can be explained by the repression of the iron exporter ferroportin upon palmitate and/or insulin treatment. While during palmitate treatment the activation of the iron regulatory hormone hepcidin may contribute to reducing ferroportin protein levels in a cell-autonomous manner, insulin treatment decreases ferroportin transcription via the PI3K/AKT and Ras/Raf/MEK/ERK signaling pathways. CONCLUSION: Repression of ferroportin at the transcriptional and post-transcriptional level may contribute to iron accumulation in hepatocytes observed in a subset of patients with T2DM.

Co-clinical Modeling of the Activity of the BET Inhibitor Mivebresib (ABBV-075) in AML.

BACKGROUND/AIM: The therapeutic potential of bromodomain and extra-terminal motif (BET) inhibitors in hematological cancers has been well established in preclinical and early-stage clinical trials, although as of yet, no BETtargeting agent has achieved approval. To add insight into potential response to mivebresib (ABBV-075), a broadspectrum BET inhibitor, co-clinical modeling of individual patient biopsies was conducted in the context of a Phase I trial in acute myeloid leukemia (AML). MATERIALS AND METHODS: Co-clinical modeling involves taking the patient's biopsy and implanting it in mice with limited passage so that it closely retains the original characteristics of the malignancy and allows comparisons of response between animal model and clinical data. Procedures were developed, initially with neonate NOD/Shi-scid-IL2rγnull (NOG) mice and then optimized with juvenile NOG-EXL as host mice, eventually resulting in a robust rate of engraftment (16 out of 26, 62%). RESULTS: Results from the co-clinical AML patient-derived xenograft (PDX) modeling (6 with >60% inhibition of bone marrow blasts) were consistent with the equivalent clinical data from patients receiving mivebresib in monotherapy, and in combination with venetoclax. The modeling system also demonstrated the activity of a novel BD2-selective BET inhibitor (ABBV-744) in the preclinical AML setting. Both agents were also highly effective in inhibiting blast counts in the spleen (10/10 and 5/6 models, respectively). CONCLUSION: These findings confirm the validity of the model system in the co-clinical setting, establish highly relevant in vivo models for the discovery of cancer therapy, and indicate the therapeutic value of BET inhibitors for AML and, potentially, myelofibrosis treatment.

Balance Assessment of Children with Sensorineural Hearing Loss.

This study aimed to assess the balance function in children with sensorineural hearing loss (SNHL) using different tests to assess vestibulospinal pathway and tests to assess vestibular system and to compare the result obtained with those of children with normal hearing sensitivity. Detailed balance assessment was done for 15 children with severe to profound SNHL and 15 children with normal hearing sensitivity in the age range of 6-10 years. The audiological evaluation included pure-tone audiometry, speech audiometry, immittance evaluation, otoacoustic emission, vestibular evoked myogenic potential (cervical VEMP and ocular VEMP), and tests to assess vestibulospinal pathway and cerebellar function, such as Romberg test, Fukuda stepping test, Tandem gait test, and Finger-to-nose test. cVEMP and oVEMP were absent in 8 ears (27%) of a total of 30 ears with SNHL. Statistical analysis shows no significant difference between latency and amplitude of cVEMP peaks and latency of oVEMP peaks across groups. Significant reduction of oVEMP peaks amplitude was seen in children with SNHL compared to children with normal hearing. Fukuda stepping test showed an abnormal response in 2 children with SNHL (13%) and one child could not perform tandem gait test (7%). Children with SNHL showed an evident abnormality on the balance assessment test results. The abnormal function of the vestibular system and the vestibulospinal pathway can compromise the child's motor development and thus needs investigation early in life.

Robust Detection of Parkinson's Disease Using Harvested Smartphone Voice Data: A Telemedicine Approach.

Introduction: Parkinson's disease affects over 10 million people globally, and ∼20% of patients with Parkinson's disease have not been diagnosed as such. The clinical diagnosis is costly: there are no specific tests or biomarkers and it can take days to diagnose as it relies on a holistic evaluation of the individual's symptoms. Existing research either predicts a Unified Parkinson Disease Rating Scale rating, uses other key Parkinsonian features such as tapping, gait, and tremor to diagnose an individual, or focuses on different audio features. Methods: In this article, we present a classification approach implemented as an iOS App to detect whether an individual has Parkinson's using 10-s audio clips of the individual saying "aaah" into a smartphone. Results: The 1,000 voice samples analyzed were obtained from the mPower (mobile Parkinson Disease) study, which collected 65,022 voice samples from 5,826 unique participants. Conclusions: The experimental results comparing 12 different methods indicate that our approach achieves 99.0% accuracy in under a second, which significantly outperforms both prior diagnosis methods in the accuracy achieved and the efficiency of clinical diagnoses.

A rare case of CNS hemangiopericytoma presenting with papilledema.

Hemangiopericytoma rarely affects the central nervous system (CNS) and usually presents to neurologists with neurological symptoms. We report a rare case of large CNS hemangiopericytoma which presented to an ophthalmologist with only signs of mild defective vision and papilledema.

Performance Evaluation of a Generative Adversarial Network for Deblurring Mobile-phone Cervical Images.

Visual examination forms an integral part of cervical cancer screening. With the recent rise in smartphone-based health technologies, capturing cervical images using a smartphone camera for telemedicine and automated screening is gaining popularity. However, such images are highly prone to image corruption, typically out-of-focus target or camera shake blur. In this paper, we applied a generative adversarial network (GAN) to deblur mobile-phone cervical (MC) images, and we evaluate the deblur quality using various measures. Our evaluation process is three-fold: first, we calculate the peak signal to noise ratio (PSNR) and the structural similarity (SSIM) of a test dataset with ground truth availability. Next, we calculate the perception based image quality evaluator (PIQE) score of a test dataset without ground truth availability. Finally, we classify a dataset of blurred and the corresponding deblurred images into normal/abnormal MC images. The resulting change in classification accuracy was our final assessment. Our evaluation experiments show that deblurring of MC images can potentially improve the accuracy of both manual and automated cancerous lesion screening.

Oligonucleotides Targeting Telomeres and Telomerase in Cancer.

Telomeres and telomerase have become attractive targets for the development of anticancer therapeutics due to their involvement in cancer cell immortality. Currently, several therapeutics have been developed that directly target telomerase and telomeres, such as telomerase inhibitors and G-quadruplex stabilizing ligands. Telomere-specific oligonucleotides that reduce telomerase activity and disrupt telomere architecture are also in development as novel anticancer therapeutics. Specifically, GRN163L and T-oligos have demonstrated promising anticancer activity in multiple cancers types via induction of potent DNA damage responses. Currently, several miRNAs have been implicated in the regulation of telomerase activity and may prove to be valuable targets in the development of novel therapies by reducing expression of telomerase subunits. Targeting miRNAs that are known to increase expression of telomerase subunits may be another strategy to reduce carcinogenesis. This review aims to provide a comprehensive understanding of current oligonucleotide-based anticancer therapies that target telomeres and telomerase. These studies may help design novel therapeutic approaches to overcome the challenges of oligonucleotide therapy in a clinical setting.

Current Molecular-Targeted Therapies in NSCLC and Their Mechanism of Resistance.

Lung cancer is treated with many conventional therapies, such as surgery, radiation, and chemotherapy. However, these therapies have multiple undesirable side effects. To bypass the side effects elicited by these conventional treatments, molecularly-targeted therapies are currently in use or under development. Current molecularly-targeted therapies effectively target specific biomarkers, which are commonly overexpressed in lung cancers and can cause increased tumorigenicity. Unfortunately, several molecularly-targeted therapies are associated with initial dramatic responses followed by acquired resistance due to spontaneous mutations or activation of signaling pathways. Acquired resistance to molecularly targeted therapies presents a major clinical challenge in the treatment of lung cancer. Therefore, to address this clinical challenge and to improve lung cancer patient prognosis, we need to understand the mechanism of acquired resistance to current therapies and develop additional novel therapies. This review concentrates on various lung cancer biomarkers, including EGFR, ALK, and BRAF, as well as their potential mechanisms of drug resistance.

Comparison of EMT mediated tyrosine kinase inhibitor resistance in NSCLC.

In the United States, lung cancer is the second most common cancer in men and women. In 2017, 222,500 new cases and 155,870 deaths from lung cancer are estimated to have occurred. A tyrosine kinase receptor, epidermal growth factor receptor (EGFR), is over expressed or mutated in non-small cell lung cancer (NSCLC) resulting in increased cell proliferation and survival. Tyrosine kinase inhibitors (TKIs) are currently being used as therapy for NSCLC patients, however, they have limited efficacy in NSCLC patients due to acquisition of resistance. This study investigates the role of epithelial-mesenchymal transition (EMT) in the development of resistance against TKIs in NSCLC. Currently, the role of p120-catenin, Kaiso factor and PRMT-1 in reversal of EMT in T790M mutated and TKI-resistant NSCLC cells is a new line of study. In this investigation we found upregulation of cytoplasmic p120-catenin, which was co-localized with Kaiso factor. In the nucleus, binding of p120-catenin to Kaiso factor initiates transcription by activating EMT-transcription factors such as Snail, Slug, Twist, and ZEB1. PRMT-1 was also found to be upregulated, which induces methylation of Twist and repression of E-cadherin activity, thus promoting EMT. We confirmed that TKI-resistant cells have mesenchymal cell type characteristics based on their cell morphology and gene or protein expression of EMT related proteins. EMT proteins, Vimentin and N-cadherin, displayed increased expression, whereas E-cadherin expression was downregulated. Finally, we found that the knockdown of p120-catenin and PRMT-1 by siRNA or use of a PRMT-1 inhibitor Furamidine increased Erlotinib sensitivity and could reverse EMT to overcome TKI resistance.