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DNA-hypomethylating agents (HMAs) induce notable remission rates in AML/MDS patients with TP53 mutations; however, secondary resistance often develops rapidly. In the DECIDER trial (NCT00867672), elderly AML patients (also those with adverse genetics) randomized to all-trans retinoic acid (ATRA) added to decitabine (DEC) attained significantly delayed time-to-resistance. An 82-year-old patient with a non-disruptive, in-frame TP53 mutation (p.Cys238_Asn239delinsTyr, VAF 90%) and complex-monosomal karyotype attained a complete hematologic and cytogenetic remission with DEC + ATRA, with 3.7 years survival after 30 treatment cycles that were well-tolerated. Further HMA + ATRA studies appear warranted in AML/MDS patients of different genetic risk groups ineligible for more intensive treatment.Trial registration: This trial was registered at ClinicalTrials.gov identifier: NCT00867672.

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Aberrant gene expression patterns in acute myeloid leukemia (AML) with balanced chromosomal translocations are often associated with dysregulation of epigenetic modifiers. The AML1/ETO (RUNX1/MTG8) fusion protein, caused by the translocation (8;21)(q22;q22), leads to the epigenetic repression of its target genes. We aimed in this work to identify critical epigenetic modifiers, on which AML1/ETO-positive AML cells depend on for proliferation and survival using shRNA library screens and global transcriptomics approaches. Using shRNA library screens, we identified 41 commonly depleted genes in two AML1/ETO-positive cell lines Kasumi-1 and SKNO-1. We validated, genetically and pharmacologically, DNMT1 and ATR using several AML1/ETO-positive and negative cell lines. We also demonstrated in vivo differentiation of myeloblasts after treatment with the DNMT1 inhibitor decitabine in a patient with an AML1/ETO-positive AML. Bioinformatic analysis of global transcriptomics after AML1/ETO induction in 9/14/18-U937 cells identified 973 differentially expressed genes (DEGs). Three genes (PARP2, PRKCD, and SMARCA4) were both downregulated after AML1/ETO induction, and identified in shRNA screens. In conclusion, using unbiased shRNA library screens and global transcriptomics, we have identified several driver epigenetic regulators for proliferation in AML1/ETO-positive AML. DNMT1 and ATR were validated and are susceptible to pharmacological inhibition by small molecules showing promising preclinical and clinical efficacy.

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Objective: The closure of schools and other educational institutes around the world has been one of the consequences of the COVID-19 and has resulted in online teaching. To facilitate online teaching, there has been an increase in the use of smartphones and tablets among adolescents. However, such enhancement in technology use may put many adolescents at the risk of problematic use of social media. Consequently, the present study explored the direct relationship of psychological distress with social media addiction. The relationship between the two was also assessed indirectly via the fear of missing out (FoMO) and boredom proneness. Methods: A cross-sectional online survey was conducted with 505 Indian adolescents aged 12 to 17 years, studying in grades 7 to 12. Standardized tools (with some modifications to suit the context of the present study) were used to collect data. Results: The results showed significant positive associations between psychological distress, social media addiction, FoMO, and boredom proneness. Psychological distress was found to be a significant predictor of social media addiction. Moreover, FoMO and boredom proneness partially mediated the relationships between psychological distress and social media addiction. Discussion: The present study is the first to provide evidence for the specific pathways of FoMO and boredom proneness in the relationships between psychological distress and social media addiction.

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Despite routine use of DNA-hypomethylating agents (HMAs) in AML/MDS therapy, their mechanisms of action are not yet unraveled. Pleiotropic effects of HMAs include global methylome and transcriptome changes. We asked whether in blasts and T-cells from AML patients HMA-induced in vivo demethylation and remethylation occur randomly or non-randomly, and whether gene demethylation is associated with gene induction. Peripheral blood AML blasts from patients receiving decitabine (20 mg/m2 day 1-5) were serially isolated for methylome analyses (days 0, 8 and 15, n = 28) and methylome-plus-transcriptome analyses (days 0 and 8, n = 23), respectively. T-cells were isolated for methylome analyses (days 0 and 8; n = 16). We noted massive, non-random demethylation at day 8, which was variable between patients. In contrast, T-cells disclosed a thousand-fold lesser, random demethylation, indicating selectivity of the demethylation for the malignant blasts. The integrative analysis of DNA demethylation and transcript induction revealed 87 genes displaying a significant inverse correlation, e.g. the tumor suppressor gene IFI27, whose derepression was validated in two AML cell lines. These results support HMA-induced, non-random early in vivo demethylation events in AML blasts associated with gene induction. Larger patient cohorts are needed to determine whether a demethylation signature may be predictive for response to this treatment.

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The COVID-19 has caused significant public health chaos. Whether infected or uninfected, people have reported significant mental health issues during the COVID-19 pandemic. The present study explored symptoms of depression, anxiety, and stress of uninfected people with the disease over three time periods. A total of 132 participants took part in all the three phases. Data at Time 1 and Time 2 were collected during the national lockdown with 1 month apart, while data at Time 3 were collected immediately once the lockdown was uplifted in India. Participants completed the Depression, Anxiety and Stress Scale-21 online. The results indicated that despite an increase in the average number of COVID-19 cases, depression, anxiety, and stress symptoms decreased over time with the lowest level once the lockdown was ended. These results suggest that the restrictions implemented during the national lockdown led to distress, and not an increase in COVID-19 cases per se.

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The present research explored individual and group level risk factors in preventive health and panic buying behaviors during the COVID-19 pandemic in India. Perceived susceptibility, perceived severity, COVID-19 anxiety, and personal identity were considered individual-level risk factors. Group based identities such as family, religious groups, and identification with one's nation were considered as group level risk factors. Standardized scales have been used to measure all the constructs under study. Data were collected electronically from 305 Indian respondents. Hierarchical regression analysis in SPSS Version 22 was used to test the hypotheses. Results showed that personal identity and identification with the nation predicted preventive health behavior. Panic buying behavior was predicted by the location of the respondents (containment versus non-containment zones), perceived severity, and one's personal identity. The interplay of individual and social factors is reflective of both individual and collective agencies in the adoption of preventive health behaviors, while only individual-level factors led to panic buying behavior. The findings of this study have implications for curbing, managing, and reinforcing desirable and non-desirable behavior during the present pandemic as well as in the future as well.

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The study explored the relationship between social distancing and distress along with risk factors of social distancing. Further, online counseling/mental health services and perceived social support were tested as possible moderators between social distancing and distress. Valid and reliable measures were used to collect the data from 300 Indian respondents. Process use of social networking platforms was found to significantly explain social distancing. Online counseling/mental health services and perceived social support moderated the relationship between social distancing and distress. Only 16% of the respondents used online mental health services during the study period. Lack of awareness and acceptance of these services were major barriers.

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Cerebral phaeohyphomycosis refers to central nervous system infection caused by dematiaceous molds, which have many genuses. Cladophialophora bantiana is a member of the phylum ascomycota, which is found in soil samples from all over the world. This organism typically infects immunocompromised patients and associated with 70% mortality rate even after weeks of antifungal agent administration and surgical debridement. Two such cases of fungal brain abscess caused by cladophialophora bantiana were presented here. Both patients presented with complaints of headache, vomiting, drowsiness and impaired cognition. A brain biopsy together with microbiological culture and VITEK 2 helped in reaching to a final diagnosis. Key Words: Cladophialophora bantiana, Dematiaceous, Intracerebral, Phaeohyphomycosis.

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Rapidly growing cystosarcoma phyllodes tumor (PT) of the breast are rarely encountered. Distant metastases are not uncommon in malignant PTs; however, rare sites of metastases are sometimes observed. Here, we present the case of a rapidly metastasizing malignant PT in which skeletal muscle metastasis was identified on 18F-fluorodeoxyglucose-based positron emission tomography-computed tomography reflecting its aggressive course and poor prognosis.

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Daratumumab (dara) belongs to a class of monoclonal antibodies that target CD38 receptors expressed on multiple myeloma (MM) cells. It was first approved for MM treatment in 2015. The efficacy and safety of dara have been reported in many studies. In this analysis, we assessed the outcome of dara addition to standard of care for transplant-eligible newly diagnosed (ND) MM. We conducted a comprehensive search using PubMed, ClinicalTrial.gov, and Embase. Out of 435 articles, we included two randomized clinical trials. We computed the odds ratio (OR) of response rates and risk ratio (RR) of adverse effects using Cochrane RevMan version 5.4. A total of 1,292 patients were enrolled in both trials. The patients were randomized into the control group and the dara group. The dara group included 647 patients and the control group included 645 patients. The CASSIOPEIA trial reported the outcomes using dara, bortezomib (V), thalidomide (T), and dexamethasone (d) versus VTd. The GRIFFIN trial underlined the efficacy of dara, lenalidomide (R), and Vd in the dara group versus RVd in the control group. A pooled analysis of included studies showed an increased overall response rate (OR: 1.60; 95% CI: 1.06-2.41; p = 0.02; I 2 = 65%), stringent complete response (OR: 1.59; 95% CI: 1.24-2.05; p = 0.03; I 2 = 0%), and negative status for minimal residual disease (OR: 2.47; 95% CI: 1.97-3.10; p < 0.01; I 2 = 66%) in the dara group as compared to the control group. However, an increased risk of neutropenia (RR: 1.80; 95% CI: 1.60-2.03; p < 0.01) and decreased risk of peripheral neuropathy (RR: 0.92; 95% CI: 0.86-0.99; p = 0.02; I 2 = 52%) were observed in the dara group. Dara addition to the standard of care regimen for transplant-eligible NDMM has promising outcomes with increased efficacy and safety profile and manageable toxicity.

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Sydenham chorea (SC) is common in childhood with extensive differential diagnoses, including inherited disease, autoimmunity, endocrine disorders, and infections. SC due to acute rheumatic fever (ARF) is rare. Herein, we present a case of SC in an eight-year-old child who presented with choreiform movements of her face and limbs, including facial grimacing, difficulty walking, and slurred speech. She also had a runny nose and odynophagia. She had two episodes of sore throat in the last two months, and her physical examination was unremarkable except for hypertrophic tonsils and generalized hypotonia. Throat and blood culture were negative for group A streptococcus. Antistreptolysin O titer was 1139 IU/mL, and anti-deoxyribonuclease B titer was 2100 IU/mL, suggesting a recent group A streptococcal infection. Magnetic resonance imaging (MRI) of the brain revealed hyperintense signals in the thalami and corpus striatum. Echocardiogram was normal with no evidence of carditis. She was diagnosed with ARF and was commenced on amoxicillin and valproic acid. Later on, she was started on IVIG due to the persistence of chorea. Her symptoms improved, and she was discharged a week later on oral haloperidol for the next ten days.

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Pneumocystis pneumonia (PCP) is an opportunistic infection caused by Pneumocystis jirovecii. PCP due to immunosuppressive drugs is rarely reported in the literature. Herein we present a case of PCP in a 49-year-old patient who presented with progressive shortness of breath, dry cough, and low-grade fever. History revealed that he was taking prednisolone daily for his hyperactive airway disease. His temperature was 99oF, and he had bilateral crackles in the lungs with resonant wheezing. High-resolution computed tomography showed diffuse ground-glass haze and cystic lesions in the middle and upper zones of both lungs. He was commenced on intravenous ceftriaxone and methylprednisolone based on provisional diagnosis of interstitial pneumonia. However, his condition worsened. His human immunodeficiency virus (HIV) test was reactive, and his CD4+ count was 275 cells/mm3. Bronchoalveolar lavage revealed PCP by direct immunofluorescent assay. Additional serum testing revealed marked elevation of beta-D-glucan, consistent with PCP diagnosis due to glucocorticoid use. Trimethoprim-sulfamethoxazole and voriconazole were initiated, and his respiratory symptoms started improving. His respiratory condition improved on day 9, and he was discharged with follow-up.

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There is growing evidence of neurological involvement in patients with coronavirus disease 19 (COVID-19), suggesting that Guillain-Barre syndrome (GBS) can also occur with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a neurological complication. Herein, we describe a unique case of a 45-year-old male who manifested with sudden onset progressive symmetric ascending paralysis leading to quadriplegia one week after developing fever, cough, and dyspnea. On examination, he had areflexia in lower limbs and hyporeflexia in upper limbs. Hypoesthesia to fine touch and vibration distal to calf was noted. His reverse transcriptase-polymerase chain reaction (RT-PCR) was positive for COVID-19, and his cerebrospinal fluid (CSF) analysis revealed albumin-cytologic dissociation. The diagnosis of GBS was made based on clinical presentation and neurophysiological studies due to COVID-19. He was commenced on intravenous immunoglobulin, and improvement in his condition was observed. He was discharged to a rehabilitation center for regular physical therapy.

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Antisynthetase syndrome is an autoimmune condition that manifests clinically through signs and symptoms, such as interstitial lung disease, myositis, Raynaud's phenomenon, fever, hyperkeratotic fingertips (mechanic's hands), and arthritis. It is associated with antibodies against aminoacyl tRNA synthetase enzyme, the most common autoantibody being the anti-Jo-1. An 18-year-old girl presented with weakness of both the upper and lower limb, swelling and generalized body pain, difficulty in swallowing. MRI of the thigh was highly suggestive of myositis with symmetrical bilateral involvement. Based on proximal muscle weakness, elevated creatine phosphokinase (CPK), and lactate dehydrogenase (LDH), strongly positive anti-nuclear antibodies human epithelial cell type-2 (ANA-HEp2), and a normal nerve conduction velocity test with precise MRI findings, a diagnosis of polymyositis was made. She was given bolus intravenous methylprednisolone for five days, followed by oral methylprednisolone with subcutaneous methotrexate weekly. She reported a 50% improvement in muscle weakness; however, partial bulbar weakness persisted at the time of discharge. On her next follow-up, her blood investigations for auto-antibodies were done. The autoantibodies anti-Jo-1 (3+), Ro-52 (2+), and Mi-2ß (2+) were found to be positive. These investigations, coupled with the clinical features she was presenting, finally led us to conclude that it was a case of polymyositis complicated by the antisynthetase syndrome.

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The role of individual variables (COVID-19 anxiety, perceived susceptibility, perceived severity, optimistic bias and personal identity) as predictors of quality of life (QoL) during the novel coronavirus or COVID-19 pandemic is explored. Impact of group related variables (identification to family, religious group and nation) on QoL is also examined. Sample comprised 305 male and female Indian respondents, aged 18 to 78 years. Standardized measures have been utilised to assess the constructs. Results revealed that QoL was significantly influenced by individual variables (COVID-19 anxiety and personal identity) and group variables (identification with family and nation). The effect of COVID-19 anxiety and personal identity as individual variables is over and above that of demographic variables on QoL. Group variables (family and national identification) significantly impacted QoL over and above the individual variables. Findings would indeed, aid in the rehabilitation and assistance of people to live in COVID-19 crisis, and thereafter.

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Covid-19 has caused significant distress around the globe. Apart from the evident physical symptoms in infected cases, it has caused serious damage to public mental health. India, like other countries, implemented a nationwide lockdown to contain and curb the transmission of the virus. The current research is an attempt to explore psychological distress among people residing in India during the lockdown. Four hundred and three participants were asked to complete a questionnaire with questions around symptoms of depression, anxiety, stress, and family affluence. The results indicated that people who do not have enough supplies to sustain the lockdown were most affected, and family affluence was found to be negatively correlated with stress, anxiety, and depression. Among different professions, students and healthcare professionals were found to experience stress, anxiety, and depression more than others. Despite the current situation, stress, anxiety, and depression were found to be in normal ranges for mental health professionals highlighting their capabilities to remain normal in times of distress. Policymakers and other authorities may take the assistance of mental health professionals to help overcome psychological issues related to Covid-19.

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INTRODUCTION:  Stigma is a label that differentiates a person from others and associates them with unenviable attributes. There are various forms of stigma: enacted stigma, perceived stigma, and self-stigma manifesting as stereotyping and harboring negative thoughts about the stigmatized group. Stigmatization of the drug abuser leads to effects such as low self-esteem, depression, and personality changes in the stigmatized.  Objectives: The purpose of the study is to know the impact of stigma on patients receiving substance abuse treatment in the Psychiatry Department, Mayo Hospital Lahore, Pakistan. DESIGN: Cross-sectional study.  Place: Psychiatry Department, Mayo Hospital, Lahore, Pakistan Study Period: Six months (February 22, 2020, to July 18, 2020). SUBJECTS AND METHODS: A population-based cross-sectional study was conducted in a tertiary care hospital. A total of 100 patients were recruited in the study. The selection was made on laid down criterion after taking due consent. Interviews were conducted through a pretested questionnaire. Data were collected, compiled, and analyzed through SPSS version 20 (IBM Corp., Armonk, USA), and relevant frequency tables were drawn.  Results: On analyzing the data, various forms of stigma were observed: enacted stigma (81% as considered less capable), perceived stigma (99% as having difficulties in the job seeking and relationships), and self-stigma (94% in having devaluation thoughts). Self-esteem was maintained (73% were content). Social support was present (76% from family). Moderate depression was seen in 17% of participants. Over 83% of our study population is aged 21 to 40 years, 15% between ages 41 and 60 years, and only 2% ranging between ages 1 and 20. A total of 80% of the population belonged to a low socioeconomic status, and 55% of participants abused opium, heroin, or brown sugar, followed by white crystal use in 37% of the study population. The majority reported the drug abuse duration of 1-5 years (70%). CONCLUSION:  Stigma in its various forms affects the drug abuser undergoing treatment. It results in low self-esteem and mild depression. Individuals from the broader socioeconomic range can be added in future studies, and a larger population can be studied by collecting data from other tertiary care hospitals and mental healthcare facilities. They can be assessed for factors contributing to their addiction and the challenges they had to go through to get the help they needed.

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An intense itching localized to dermatomes is a rare symptom of multiple sclerosis (MS). Herein, we report a case of a 45-year-old female who presented with severe itching and tingling sensation, gait disturbance, and bilateral paresthesia for one week. She also had a history of multiple admission in the hospital due to recurrent walking abnormalities and numbness and tingling of both hands associated with intermittent psychiatric symptoms. The neurological examination revealed spastic quadriparesis with lower limb muscles affected more than the upper limbs, numbness, and sensory loss in the upper extremities in the glove and stocking pattern. Magnetic resonance imaging (MRI) revealed multiple small rounded periventricular plaques in both hemispheres and along the long axis of the corpus callosum (fluid-attenuated inversion recovery/FLAIR sequence), and cerebrospinal fluid analysis revealed the presence of oligoclonal bands, suggestive of MS. She was commenced on methylprednisolone and carbamazepine, leading to progressive resolution of her signs and symptoms. She was discharged with monthly natalizumab, and she was doing well on her follow-up.

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A 10-year-old boy with no past medical history presented with complaints of nausea and vomiting associated with morning headache for the last month. Ophthalmic nerve and eye exam showed diplopia and strabismus with no other significant findings on physical and neurological examination. Magnetic resonance imaging (MRI) of the brain revealed a homogenous hyperdense and enhancing mass in the pineal region. The endoscopic biopsy of the pineal region demonstrated the cells with highly pleomorphic and hyperchromatic nuclei with an increase in mitotic activity. There were many vessels but no area of vascular proliferation and necrosis. Granular bodies with eosinophilia were identified. Immunohistochemistry was positive for class III b-tubulin with epidermal growth factor receptor (EGFR) staining and glial fibrillary acidic protein (GFAP). Immunostaining was positive for p53, Phosphatase and Tensin homolog (PTEN), and oligodendrocyte transcription factor (OLIG2), while staining for cluster of differentiation (CD)34, cytokeratin (CK), human melanoma black (HMB)45, and isocitrate dehydrogenase (IDH)-R132H mutation was negative, consistent with atypical pleomorphic neoplasm of the pineal region. The patient underwent tumor resection via a sub-occipital trans-tentorial approach, followed by one dose of chemotherapy. The patient experienced a resolution of the symptom and was doing well on his bi-monthly follow up.

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Recurrent urinary tract infection (UTI) is uncommon in males, but it is a common complication of Crohn's disease (CD). Patients with CD often present with abdominal pain, diarrhea, and systemic symptoms, such as weight loss, low-grade fever, and fatigue, and rarely it can cause serious complications, such as fistulas or abscesses. Some patients with CD remain asymptomatic, which can progress to severe complications and delayed treatment. We are presenting a 22-year-old male with recurrent UTIs and no established past medical history of CD. However, on subsequent investigations, an anatomical abnormality was discovered that helped us make the diagnosis of CD. The aim of this report is to emphasize the early detection of asymptomatic CD in atypical patients, to not only decrease the risk of complications such as UTIs but also allow for early treatment intervention and better outcomes.