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Background: Infantile Ewing Sarcoma (ES) is an extremely rare disease with comparable outcomes on contemporary protocols. There is a paucity of data from India. Methods: Infants with proven ES diagnosed between January 2012 and December 2020 were retrospectively analyzed. The staging was performed using positron emission tomography-computerized tomography scan. Treated infants were administered weight-based chemotherapy. The local control was with surgery and/or radiotherapy. Results: There were 10 infants with ES with a male-to-female ratio of 2.3:1. The majority had extraosseous (90 %, n = 9) or axial primary (50 %, n = 5). Five patients with localized disease received treatment. Two died during induction chemotherapy (sepsis-1, cause unknown-1), and 3 are alive with no evidence of disease at a median follow-up of 8 years (range: 4–9). Two episodes of complicated febrile neutropenia were reported in 5 treated infants. Conclusions: ES in infants is rare and predominantly extraosseous with axial primary. Treated infants with non-metastatic disease tolerated chemotherapy well with good outcomes.

Adult hippocampal neurogenesis is a lifelong process that involves the integration of newborn neurons into the hippocampal network, and plays a role in cognitive function and the modulation of mood-related behavior. Here, we sought to address the impact of chemogenetic activation of adult hippocampal progenitors on distinct stages of progenitor development, including quiescent stem cell activation, progenitor turnover, differentiation and morphological maturation. We find that hM3Dq-DREADD-mediated activation of nestin-positive adult hippocampal progenitors recruits quiescent stem cells, enhances progenitor proliferation, increases doublecortin-positive newborn neuron number, accompanied by an acceleration of differentiation and morphological maturation, associated with increased dendritic complexity. Behavioral analysis indicated anxiolytic behavioral responses in transgenic mice subjected to chemogenetic activation of adult hippocampal progenitors at timepoints when newborn neurons are predicted to integrate into the mature hippocampal network. Furthermore, we noted an enhanced fear memory extinction on a contextual fear memory learning task in transgenic mice subjected to chemogenetic activation of adult hippocampal progenitors. Our findings indicate that hM3Dq-DREAD-mediated chemogenetic activation of adult hippocampal progenitors impacts distinct aspects of hippocampal neurogenesis, associated with the regulation of anxiety-like behavior and fear memory extinction.

Introduction: Job satisfaction is an attitudinal variable representing the extent to which people like or dislike their jobs. It is a critical factor influencing healthcare quality, patient outcomes, and overall well-being in medical professionals. This study aimed to determine Job Satisfaction among medical doctors in Nepal. Methods: A descriptive cross-sectional study was conducted among medical doctors of Nepal between June 2023 and August 2023 after obtaining ethical approval from the Ethical Review Board of Nepal Health Research Council. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 380 participants, 63 (16.58%) (12.84-20.32 at 95% Confidence Interval) expressed satisfaction. The number of satisfied participants above 40 years were 10 (16%) and less than 40 years were 53 (84%). Out of 63, 46 (73.02%) were male and 17 (26.98%) were females. Conclusions: Job satisfaction among doctors practicing in Nepal was found to be lower than the studies conducted in similar settings.

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is often modeled in Fmr1 knockout mice where the RNA-binding protein FMRP is absent. Here, we show that in Fmr1-deficient mice, RNA mis-splicing occurs in several brain regions and peripheral tissues. To assess molecular mechanisms of splicing mis-regulation, we employed N2A cells depleted of Fmr1. In the absence of FMRP, RNA-specific exon skipping events are linked to the splicing factors hnRNPF, PTBP1, and MBNL1. FMRP regulates the translation of Mbnl1 mRNA as well as Mbnl1 RNA auto-splicing. Elevated Mbnl1 auto-splicing in FMRP-deficient cells results in the loss of a nuclear localization signal (NLS)-containing exon. This in turn alters the nucleus-to-cytoplasm ratio of MBNL1. This redistribution of MBNL1 isoforms in Fmr1-deficient cells could result in downstream splicing changes in other RNAs. Indeed, further investigation revealed that splicing disruptions resulting from Fmr1 depletion could be rescued by overexpression of nuclear MBNL1. Altered Mbnl1 auto-splicing also occurs in human FXS postmortem brain. These data suggest that FMRP-controlled translation and RNA processing may cascade into a general dys-regulation of splicing in Fmr1-deficient cells.

BackgroundThe role of artificial intelligence and radiomics in prediction model development in cancer has been increasing every passing day. Cervical cancer is the 4th most common cancer in women worldwide, contributing to 6.5% of all cancer types. The treatment outcome of cervical cancer patients varies and individualized prediction of disease outcome is of paramount importance.PurposeThe purpose of this study is to develop and validate the digital signature for 5-year overall survival prediction in cervical cancer using robust CT radiomic and clinical features.Materials and MethodsPretreatment clinical features and CT radiomic features of 68 patients, who were treated with chemoradiation therapy in our hospital, were used in this study. Radiomic features were extracted using an in-house developed python script and pyradiomic package. Clinical features were selected by the recursive feature elimination technique. Whereas radiomic feature selection was performed using a multi-step process i.e., step-1: only robust radiomic features were selected based on our previous study, step-2: a hierarchical clustering was performed to eliminate feature redundancy, and step-3: recursive feature elimination was performed to select the best features for prediction model development. Four machine algorithms i.e., Logistic regression (LR), Random Forest (RF), Support vector classifier (SVC), and Gradient boosting classifier (GBC), were used to develop 24 models (six models using each algorithm) using clinical, radiomic and combined features. Models were compared based on the prediction score in the internal validation.ResultsThe average prediction accuracy was found to be 0.65 (95% CI: 0.60–0.70), 0.72 (95% CI: 0.63–0.81), and 0.77 (95% CI: 0.72–0.82) for clinical, radiomic, and combined models developed using four prediction algorithms respectively. The average prediction accuracy was found to be 0.69 (95% CI: 0.62–0.76), 0.79 (95% CI: 0.72–0.86), 0.71 (95% CI: 0.62–0.80), and 0.72 (95% CI: 0.66–0.78) for LR, RF, SVC and GBC models developed on three datasets respectively.ConclusionOur study shows the promising predictive performance of a robust radiomic signature to predict 5-year overall survival in cervical cancer patients.

Introduction In locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS).Methods and analysis Radiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years.Ethics and dissemination The trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained.Trial registration number The trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916).

Fragile X Syndrome is a neuro-developmental disorder caused by the silencing of the FMR1 gene, resulting in the loss of its protein product, FMRP. FMRP binds mRNA and represses general translation in the brain. Transcriptome analysis of the Fmr1-deficient mouse hippocampus reveals widespread dysregulation of alternative splicing of pre-mRNAs. Many of these aberrant splicing changes coincide with those found in post-mortem brain tissue from individuals with autism spectrum disorders (ASDs) as well as in mouse models of intellectual disability such as PTEN hamartoma syndrome (PHTS) and Rett Syndrome (RTT). These splicing changes could result from chromatin modifications (e.g., in FXS, RTT) and/or splicing factor alterations (e.g., PTEN, autism). Based on the identities of the RNAs that are mis-spliced in these disorders, it may be that they are at least partly responsible for some shared pathophysiological conditions. The convergence of splicing aberrations among these autism spectrum disorders might be crucial to understanding their underlying cognitive impairments.

Wilms tumour is the commonest renal tumour in children with peak age group of 2–5 years [1,2]. It commonly presents as an incidentally detected abdominal mass; however fever, hematuria and hypertension may also be seen [1]. Extra-renal Wilms tumour is extremely rare, with an incidence of 0.5%–1% [3,4]. Wilms tumour, most commonly metastasizes to the lungs, followed by lymph nodes and liver, however, metastasis to the bones and spinal cord at diagnosis is extremely rare [1,2,5–10]. We hereby, report an extremely rare presentation of suprarenal Wilms tumour with intraspinal metastases. Our case highlights the high degree of vigilance as well as timely intervention with multimodality therapy required to improve the outcomes in the setting of advanced metastatic disease; notwithstanding the potentially irreversible neurological weakness in the absence of optimal intervention.

Introduction: Recent research demonstrates burnout prevalence rates as high as 76% in emergency medicine (EM) residents. In 2017 the Accreditation Council for Graduate Medical Education (ACGME) required that all training programs provide dedicated wellness education for their trainees as a requirement for accreditation. We aimed to conduct a systematic review of published wellness interventions conducted in EM residency programs following the implementation of the 2017 ACGME Common Program Requirements change in order to characterized published intervention and evaluate their effectiveness. Methods: We applied a published approach to conducting systematic reviews of the medical education literature. We performed a search of the literature from January 1, 2017–February 1, 2020. Studies were included for final review if they described a specific intervention and reported outcomes with the primary goal of improving EM resident wellness. Outcomes were characterized using the Kirkpatrick training evaluation model. Results: Eight of 35 identified studies met inclusion criteria. Most described small convenience samples of EM residents from single training programs and used the satisfaction rates of participants as primary outcome data. Only quantitative assessment methods were used. Studies addressed only a limited number of factors affecting resident wellness. The majority of interventions focused on personal factors, although a few also included sociocultural factors and the learning and practice environment. Conclusion: There is a relative dearth of literature in the area of research focused on interventions designed to improve EM resident wellness. Furthermore, the studies we identified are narrow in scope, involve relatively few participants, and describe programmatic changes of limited variety. Future directions include an increase and emphasis on multi-institutional studies, randomized controlled trials, qualitative methodology, and opportunities for funded research.

Unlike other pediatric extra cranial solid neoplasms, neuroblastomas have very low incidence of pulmonary metastases. Neuroblastomas also tend to encase rather than infiltrate the major vessels with very low incidence of tumor thrombus. Even in cases with inferior vena cava tumor thrombosis, pulmonary metastases are a rare occurrence. These patients usually show widespread disseminated disease at presentation. We present a rare case of adrenal neuroblastoma with tumor thrombus and bilateral pulmonary metastases at presentation. This presentation can be confused with adrenocortical carcinoma and differentiating between the two is essential for further management.

Standard guidelines for the management of early and locally advanced cervical cancer are available from various academic consortiums nationally and internationally. However, implementing standard-of-care treatment poses unique challenges within low- and middle-income countries, such as India, where diverse clinical care practices may exist. The National Cancer Grid, a consortium of 108 institutions in India, aims to homogenize care for patients with cervical cancer by achieving consensus on not only imaging and management, but also in addressing potential solutions to prevalent challenges that affect the homogenous implementation of standard-of-care treatment. These guidelines therefore represent a consensus statement of the National Cancer Grid gynecologic cancer expert group and will assist in homogenization of the therapeutic management of patients with cervical cancer in India.

In eukaryotic cells, inefficient splicing is surprisingly common and leads to the degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here, we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these “decay-promoting” introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction in the levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay-promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate the regulation of gene expression. Based on the identification of multiple additional Mmi1 targets, including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation.

Piano tuning is known to be difficult because the stiffness of piano strings causes the tones produced to be inharmonic. Aural tuning is time consuming and requires the help of a professional. This motivates the question of whether this process can be automated. Attempts at automatic tuning are usually assessed by comparing the Railsback curve of the results with the curve of a professional tuner. In this paper we determine a simple and reliable rule for tuning the high tones of a piano with the help of a listening test. This rule consists of matching the two tones in an octave interval so that the first partial frequency of the upper tone becomes exactly the same as the second partial frequency of the lower tone. This rule was rated best among four tuning rules that were compared in the test. The results found are explained using a beat-based analysis, and are consistent with some previous studies. They are also tested against the existing method of using Railsback curves, and it is shown that comparison using Railsback curves is an unreliable method of assessing different tunings. The findings from this paper can be used to create a complete automatic tuner that could make the process of piano tuning quick and inexpensive.

Neuroblastoma is the third common tumor in children. Imaging plays an important role in the diagnosis, staging, treatment planning, response evaluation and in follow-up of a case of Neuroblastoma. The International Neuroblastoma Risk Group task force has recently introduced an imaging-based staging system and laid down guidelines for uniform reporting of imaging studies. This review is an update on imaging in neuroblastoma, with emphasis on these guidelines.

Primary vulvar Ewing sarcoma (ES)/PNET is an uncommonly documented tumor, especially with molecular results. A 10-year-old girl presented with left vulvar swelling, a year ago. Her abdominopelvic ultrasound revealed a 12 cm × 8 cm sized, mixed echogenic blood-filled lesion in the left vulva; radiologically considered as a hematoma. Vulvectomy revealed a multinodular grey-brown tumor, microscopically comprising malignant round cells. Immunohistochemically, tumor cells diffusely expressed MIC2/CD99 and Fli1 and subsequently displayed EWSR1 rearrangement, confirming diagnosis of ES/PNET. Subsequently, PET-CT scan revealed residual local lesion with lung metastases. The patient was induced on EFT 2001 chemotherapy protocol. Three months after chemotherapy completion, there was no metabolically active disease on PET scan. Four months later, MRI disclosed recurrent primary and metastatic pulmonary lesions. She was planned for scar excision and adjuvant radiotherapy, but unfortunately defaulted further treatment. This forms the eighth case of primary vulvar ES/PNET confirmed with molecular cytogenetic result, underscoring therapeutic value of objective diagnosis in such cases.

Tube arcing artifact is known to be caused by a temporary short circuit in the X-ray tube causing momentary loss of X-ray output. It is seen as near-parallel and an equidistant streak pattern on transaxial computed tomography (CT) images and as a "horizontal" hypodense band on the coronal and sagittal CT images. This artifact can be a random occurrence and was caused in this particular case due to voltage fluctuations in the high-voltage supply transformer supplying the rotor of the anode in the X-ray tube. This problem was initially corrected by reducing the tube voltage to 120 kV from the original 140 kV and, subsequently, replacing the faulty transformer. This kind of artifact, which is a very rare situation, can affect the image quality, and could also be an early sign of equipment failure. To the authors′ knowledge, such an artifact has not been reported till date in a clinical scenario. Hence, we would like to report a rare situation of tube arcing artifact along with a unique remedy.

Filtered Back-Projection (FBP) has become an outdated image reconstruction technique in new-generation positron emission tomography (PET)/computed tomography (CT) scanners. Iterative reconstruction used in all new-generation PET scanners is a much improved reconstruction technique. Though a well-calibrated PET system can only be used for clinical imaging in few situations like ours, when compromised PET scanner with one PET module bypassed was used for PET acquisition, FBP with sinogram correction proved to be a better reconstruction technique to minimize streak artifact present in the image reconstructed by the iterative technique.

Background: Incidental colonic uptake of 18F-flurodeoxyglucose (FDG) is not an infrequent finding encountered during whole body positron emission tomography (PET) imaging. Almost all studies on this topic are in Western populations, which have a markedly different epidemiological profile for colorectal premalignant and malignant conditions as compared to that of the Indian subcontinent. Aim: The purpose of this study was to assess the etiology of incidentally detected focal FDG uptake in the colon by comparing it with colonoscopy and histopathology. Materials and Methods: Electronic medical records of patients who underwent FDG PET/computed tomography (CT) at our institution for a 2½-year period from January 2009 to July 2011 were reviewed. There were 32 out of 9000 (0.35%) patients whose PET/CT reports mentioned incidental focal colonic FDG uptake, of which 24 patients subsequently underwent colonoscopy. Lesions which appeared neoplastic on colonoscopy were confirmed with histopathology obtained after biopsy or surgery. Colonoscopy and pathology findings were considered as gold standard. Results: Among the 24 patients who underwent a colonoscopy, 3 patients had normal findings (12.5%). A positive colonoscopy was noted in 21 patients (87.5%) with the lesion coinciding with the location described in the PET/CT report. Adenomatous polyps were detected in 12 patients (37.5%), whereas in 8 patients (25%) malignant lesions were confirmed [adenocarcinoma n = 5, non-Hodgkin′s lymphoma (NHL) n = 2, malignant melanoma n = 1]. In one patient, colonic uptake was diagnosed as inflammatory. The mean standardized uptake value max (SUV max ) for the 12 premalignant lesions was 16.9 ± 9.6 (range 7.5-37.4) and the mean SUV max for the 8 malignant lesions was 12.9 ± 5.5 (range 6.7-21.6). The difference in SUV max between the premalignant adenomatous polyps and the malignant lesions was not statistically significant (P = 0.316). Conclusions: Our study shows that a significant proportion of patients (62.5%, 20/32) showing an incidental focal FDG uptake will harbor premalignant (adenomatous polyps) or malignant lesions, and further evaluation with colonoscopy and biopsy is warranted in such cases.

Somatostatin receptor scintigraphy is considered as a comprehensive imaging modality for many neuroendocrine tumors. Multiple radiotracers using combinations of gamma or positron emitting radionuclides and tracers are now available. Newer radiopharmaceuticals using 99m Tc labeled with TOC, TATE, NOC are good alternatives to the 68 - Gallium radiotracers where the PET facility is not available. The pictoral depicts the role of SRS using 99mTC - HYNIC -TOC radiotracers in staging and treatment planning of NETs. Characterization of the tumor biology using combined SRS and FDG PET/CT is also demonstrated with a proposed categorization method. The emerging role of SRS in tailored targeted radionuclide therapy is outlined in brief.

Colorectal cancer (CRC) can recur locoregionally or at distant sites. Timely diagnosis of recurrence is of paramount importance, as radical treatment of the localized disease can prolong survival. Fluorodeoxyglucose positron emission tomography / computed tomography (PET / CT) is routinely used in restaging and surveillance of colorectal cancer, as it can demonstrate recurrent disease with good accuracy. This article illustrates the spectrum of standard as well as unusual patterns of local recurrence and distant metastases of colorectal cancer.

PET/CT is a new modality with integration of PET and CT systems. In India, since December 2004 there has been a steady increase in the number of imaging systems. From stand-alone PET/CT systems with on-site cyclotrons, mostly in the government sector, the modality has matured to such an extent that, today, the majority of the PET/CT scanners and cyclotrons are in the private setup; also, scanners situated in different locations (and even different cities) share the isotope produced from one cyclotron. This shows how much this field has developed and reflects the confidence of the end users. The current status of PET/CT in India is indeed healthy and heartening and the future certainly looks promising.

A key question in the field of RNA regulation is how some exosome substrates, such as spliceosomal snRNAs and telomerase RNA, evade degradation and are processed into stable, functional RNA molecules. Typical feature of these non-coding RNAs is presence of the Sm complex at the 3'end of the mature RNA molecule. Here, we report that in Saccharomyces cerevisiae presence of intact Sm binding site is required for the exosome-mediated processing of telomerase RNA from a polyadenylated precursor into its mature form and is essential for its function in elongating telomeres. Additionally, we demonstrate that the same pathway is involved in the maturation of snRNAs. Furthermore, the insertion of an Sm binding site into an unstable RNA that is normally completely destroyed by the exosome, leads to its partial stabilization. We also show that telomerase RNA accumulates in Schizosaccharomyces pombe exosome mutants, suggesting a conserved role for the exosome in processing and degradation of telomerase RNA. In summary, our data provide important mechanistic insight into the regulation of exosome dependent RNA processing as well as telomerase RNA biogenesis.