Modified DeeplabV3+ with multi-level context attention mechanism for colonoscopy polyp segmentation.

The development of automated methods for analyzing medical images of colon cancer is one of the main research fields. A colonoscopy is a medical treatment that enables a doctor to look for any abnormalities like polyps, cancer, or inflammatory tissue inside the colon and rectum. It falls under the category of gastrointestinal illnesses, and it claims the lives of almost two million people worldwide. Video endoscopy is an advanced medical imaging approach to diagnose gastrointestinal disorders such as inflammatory bowel, ulcerative colitis, esophagitis, and polyps. Medical video endoscopy generates several images, which must be reviewed by specialists. The difficulty of manual diagnosis has sparked research towards computer-aided techniques that can quickly and reliably diagnose all generated images. The proposed methodology establishes a framework for diagnosing coloscopy diseases. Endoscopists can lower the risk of polyps turning into cancer during colonoscopies by using more accurate computer-assisted polyp detection and segmentation. With the aim of creating a model that can automatically distinguish polyps from images, we presented a modified DeeplabV3+ model in this study to carry out segmentation tasks successfully and efficiently. The framework's encoder uses a pre-trained dilated convolutional residual network for optimal feature map resolution. The robustness of the modified model is tested against state-of-the-art segmentation approaches. In this work, we employed two publicly available datasets, CVC-Clinic DB and Kvasir-SEG, and obtained Dice similarity coefficients of 0.97 and 0.95, respectively. The results show that the improved DeeplabV3+ model improves segmentation efficiency and effectiveness in both software and hardware with only minor changes.

Higher intake of ß-glucan impairs reproduction in a female teleost, Tor putitora (Hamilton, 1822).

Although the immuno-modulatory and stress-relieving properties of ß-glucan is well elucidated in humans and other animal models, including fish, its role as a dietary supplement on reproduction is extremely scarce. Therefore, in this study, adult female fish were fed one of four test diets having 0 (control), 0.5, 1, and 1.5% ß-D-glucan for 130 days and its effect on reproductive performance, ovarian and liver histology, sex hormones, and transcript abundance of selected reproduction-related genes was assessed. Low dietary intake of ß-glucan improved fertilization and hatching rates (p<0.05). The relative fecundity and percentage of spawning females were higher (non-significant) in 0.5% ß-glucan-fed groups. Surprisingly, even after 130 days, spawning did not occur in 1.5% ß-glucan-fed individuals. Irrespective of ß-glucan intake, all the brooders recorded similar plasma 17ß-estradiol and maturation-inducing hormone (p>0.05). Higher intake of ß-glucan (1.5%) upregulated aromatase genes without a parallel increase in 17ß-estradiol. However, plasma vitellogenin increased with increasing ß-glucan up to 1.0% then declined at 1.5% (p<0.05). The fish that received control, 0.5, and 1.5% ß-glucan recorded similar vitellogenin levels in their plasma. Significantly higher plasma cortisol was evidenced in 1.5% ß-glucan fed brooders (p<0.05). Histologically, higher follicular atresia and leaking of yolk material was evidenced in 1.5% ß-glucan-fed group. Liver histology revealed the highest nutrient/lipid accumulation in fish that received 1.0% and 1.5% ß-glucan. This study demonstrated the stimulatory effect of ß-glucan intake at a lower dose (0.5%) on reproduction. However, higher intake (1.5%) could perturb normal reproductive function in a fish model and caused an increased number of atretic follicles leading to spawning/reproductive failure.

Danazol for the Treatment of Myelodysplastic Syndromes: A Systematic Review.

Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched for relevant publications from inception June 1, 1950, until June 28, 2022. The studies were screened by title and abstract, followed by full-text screening. The quality of the included studies was assessed via a prespecified set of questionnaires. Data on the efficacy measures and adverse outcomes were extracted and included in a descriptive summary. Results Nine studies consisting of 246 participants were included in our review. The overall quality of the included studies was fair. The age of the participants ranged from 61 to 78 years. In all 9 studies, more male patients had been enrolled than female patients. Overall, a proportion of patients in all the studies reported a desired major response to a danazol dose of 400 to 800 mg/day. Few studies did not observe any improvement in the platelet count. Elevated liver enzyme levels, weight gain, headache, dermatitis, and weakness were the most common AEs observed. One study reported a fatal intracerebral hemorrhage in 1 participant. Conclusions Danazol has been effective in increasing platelet count and hemoglobin level. Despite a few AEs, danazol is a safe drug for the treatment of patients with myelodysplastic syndromes.

Drug reaction with eosinophilia and systemic symptoms syndrome secondary to isoniazid and ethambutol: a case report and literature review.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, potentially life-threatening condition precipitated by reaction of therapeutic drugs. The prevalence of potential antitubercular therapy (ATT)-induced DRESS is 1.2%. Case presentation: A 71-year-old female patient after 5 weeks of starting ATT complaints of fever, vomiting, dizziness, and generalized itchy maculopapular rash over the body. It was associated with marked eosinophilia (absolute eosinophil count 3094 cell/mm3, 36% in peripheral blood smear). Discussion: Fever, rash, lymphadenopathy, and internal organ involvement with marked eosinophilia constitute the major clinical manifestations of DRESS. RegiSCAR scoring system is usually used to diagnose DRESS. Identification of the culprit drug is based on the temporal correlation of symptoms with drug exposure and rechallenge test, patch test and lymphocytic transformation tests may be valuable adjunctive tools. Treatment includes withdrawal of offending agent and use of topical or systemic corticosteroids, antihistamines, cyclosporin or JAK inhibitor with clinical judgement. Conclusion: Clinicians from the tuberculosis burden region must be aware of DRESS associated with ATT and they must counsel the patient properly before prescription and manage them without delay if DRESS ensues.

Nonparaneoplastic anti-NMDA receptor encephalitis in an adolescent girl: a case report.

Anti-N-methyl D-aspartate (NMDA) receptor encephalitis is an autoimmune neurologic disorder that classically presents with psychiatric, neurologic, and autonomic symptoms, often with a viral prodrome. Case presentation: A 17-year-old female presented to the hospital with an 11-day history of fever, altered behavior, abnormal body movements, and altered sensorium. Upon examination, she was found to be febrile, tachycardic, and tachypneic, with a Glasgow Coma Scale score of 8. Discussion: The diagnosis of anti-NMDA receptor encephalitis is usually confirmed by the presence of anti-NMDA receptor antibodies in the cerebrospinal fluid. The first-line treatment options include steroids, intravenous immunoglobulin, and plasmapheresis, while second-line therapies such as rituximab and cyclophosphamide may be necessary for some patients. While most patients respond well to treatment, complications can arise, and as in this case, death can occur. Conclusion: New onset symptoms like alteration in behavior, abnormal body movement, altered sensorium, and psychiatric symptoms in a young female should raise suspicion of this disease. Immunotherapy is promising; however, anticipation and management of complication are essential in reducing mortality.

Essential Thrombocythemia among Patients with Myeloproliferative Neoplasms in Haematology Unit of a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Essential thrombocythemia, a myeloproliferative condition with an increased number of circulating platelets, is a rare hematological malignancy. The aim of the study is to find out the prevalence of essential thrombocythemia among patients with myeloproliferative neoplasms presenting in haematology unit of a tertiary care centre. Methods: This was a descriptive cross-sectional study at a tertiary care centre from September, 2020 to September, 2021 (Reference number: 48 (6-11) E2077/076). All the patients with a diagnosis of essential thrombocythemia and willing to give consent were included in the study while the patients with incomplete investigations were excluded. A sample size of 72 patients was taken and convenience sampling was done. Data were entered in Microsoft Excel 2010 and analysis was done by the Statistical Package for the Social Sciences Version 22.0. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data along with mean and standard deviation for continuous data. Results: Among 72 patients with myeloproliferative neoplasms, the prevalence of essential thrombocythemia was found to be 17 (23.61%) (13.80-33.42 at a 95% Confidence Interval). The mean age of patients was 55.41±11.20 years with a male to female ratio of 9:8. The mean hemoglobin level and platelet count in patients were found to be 11.20±2.1 g/dl and 677000±262067.70 cells/mm3. Twelve (70.58%) of total patients were under low risk of essential thrombocythemia while 3 (17.64%) of them were at high risk. Conclusions: The prevalence of essential thrombocythemia was similar to other studies done in similar settings. Keywords: essential thrombocythemia; hematology; mutation.

Gas chromatography-mass spectrometry (GC-MS) profiling reveals substantial metabolome diversity in seabuckthorn (Hippophae rhamnoides L.) berries originating from different geographical regions in the Indian Himalayas.

INTRODUCTION: Seabuckthorn (Hippophae rhamnoides L.) is a high-altitude plant with immense medicinal, nutritional, and therapeutic value. Earlier studies have documented the presence of various useful bioactive substances in this species; however, comprehensive metabolome profiling of seabuckthorn berries originating from different regions of the Indian Himalayas has not been undertaken. OBJECTIVE: Metabolomic profiling of seabuckthorn berries originating from different geographical sites in the Himachal Pradesh and Jammu & Kashmir regions of the Indian Himalayas was performed by using gas chromatography-mass spectrometry. MATERIALS AND METHODS: The GC-MS metabolome profiles of seabuckthorn berries collected from different sites (altitude 1,400-4,270 m; average temperature 8°C-27°C) were subjected to multivariate analysis following principal component analysis and hierarchical clustering analysis. RESULTS: The GC-MS results showed substantial variability for berry metabolites, including fatty acids, alkyl ethers, and alkyl esters. Fatty acids and their esters were mainly responsible for the variation in the berry metabolome. The metabolite expression profile heat map revealed two distinct groups of seabuckthorn berries originating from Himachal Pradesh (Lahaul and Spiti) and Jammu & Kashmir (Leh, Nubra, and Kargil), the former showing higher expression of metabolites. Interestingly, a strong negative association existed between altitude and the amounts of metabolites such as amides, alkyl esters, alcohols, sugars, and sugar esters. In contrast, temperature showed a strong positive association with ketone and alkyl ether levels. CONCLUSION: GC-MS profiling provides important phytochemical indicators to distinguish between seabuckthorn berries from different geographical sites. Our metabolome profiling analysis generated valuable information that will be useful in the formulation of various seabuckthorn products, benefiting farmers and industries.

Identification of stage-specific differentially expressed genes and SNPs in gastric cancer employing RNA-Seq based transcriptome profiling.

We analysed over 400 million reads obtained from Illumina sequencing of six pairs of libraries representing two each of stage I, II, and III gastric tumors and corresponding normal tissues to identify differentially expressed genes (DEGs), single nucleotide polymorphisms (SNPs), and transcription factors (TFs). In total, 2207 DEGs including 972 upregulated genes and 1235 downregulated genes were detected. Of these, several stage-specific signature genes were identified. The protein-protein interaction networks involving DEGs and TFs were constructed. The KEGG pathway analysis of SNP harbouring genes revealed their involvement in different cancer related pathways like apoptosis, mTOR pathway, and MAPK signaling pathway. The SNP analysis showed implication of host genes in GO categories like immune system process, regulation of signaling, response to stress, and transport. A biased chromosomal distribution of DEGs and SNP harbouring genes was observed. Our study would provide further insights into the complex regulatory mechanisms operating during gastric tumorigenesis.

MicroRNAs: potential biomarkers for diagnosis and prognosis of different cancers.

A thorough understanding of the tumor environment and underlying genetic factors helps in the better formulation of cancer management strategies. Availability of efficient diagnostic and prognostic biomarkers facilitates early detection and progression of the disease. MicroRNAs affect different biological processes participating in tumorigenesis through regulation of their target genes. An expanding list of unique RNAs and understanding of their regulatory role has opened up a new field in cancer research. Based on a comprehensive literature search, we identified 728 miRNAs dysregulated in sixteen cancer types namely bladder cancer (BC), breast cancer (BrC), cervical cancer (CC), colorectal cancer (CRC), esophageal cancer (EC), endometrial cancer (EnC), gastric cancer (GC), hepatocellular cancer (HCC), head and neck squamous cell cancer (HNSCC), lung cancer (LC), ovarian cancer (OC), pancreatic cancer (PC), prostate cancer (PrC), renal cell cancer (RCC), skin cancer (SC), and thyroid cancer (TC). Expression of 43 miRNAs was either upregulated or downregulated in six or more of these cancers. Finally, seven miRNAs namely mir-18a, mir-21, mir-143/145, mir-210, mir-218, mir-221, showing maximum dysregulation, either up- or down-regulation in the majority of cancers, were selected for a detailed presentation of their expression and evaluation of their potential as biomarkers in the diagnosis and prognosis of different cancers.

Microsatellite instability in mismatch repair and tumor suppressor genes and their expression profiling provide important targets for the development of biomarkers in gastric cancer.

We evaluated microsatellite instability (MSI) in selected mismatch repair (MMR) and tumor suppressor (TS) genes with a view to exploring genetic changes associated with the occurrence of gastric cancer (GC). Moreover, expression of MSI positive genes was measured to get insights into molecular events operating in the tumor microenvironment. We anticipated discovering new molecular targets with potential as molecular biomarkers of gastric cancer. Of the 13 genes screened, we observed 15% to 52.5% MSI at eight microsatellite loci located in 3' UTR and coding regions of six genes (TGFBR2, PDCD4, MLH3, DLC1, MSH6, and MSH3). The union probability of different combinations of unstable microsatellite loci unveiled a set of four MSI markers from TGFBR2, PDCD4, MLH3, and MSH3 genes that allows detection of up to 85% incidences of GC. Significant downregulation of MLH3, PDCD4, TGFBR2, and DLC1 genes was observed in tumor tissues. Protein structure analyses of two unexplored targets, MSH3 (TG4) and MSH6 (A7), with MSI in the coding region, exhibited the loss of essential domains in the encoded aberrant protein hampering its function in the MMR machinery. The molecular markers thus identified could potentially be used as MSI biomarkers for the diagnosis of gastric tumorigenesis after further validation.

Next generation sequencing-based emerging trends in molecular biology of gastric cancer.

Gastric cancer (GC) is one of the leading causes of cancer related mortality in the world. Being asymptomatic in nature till advanced stage, diagnosis of gastric cancer becomes difficult in early stages of the disease. The onset and progression of gastric cancer has been attributed to multiple factors including genetic alterations, epigenetic modifications, Helicobacter pylori and Epstein-Barr Virus (EBV) infection, and dietary habits. Next Generation Sequencing (NGS) based approaches viz. Whole Genome Sequencing (WGS), Whole Exome Sequencing (WES), RNA-Seq, and targeted sequencing have expanded the knowledge base of molecular pathogenesis of gastric cancer. In this review, we highlight recent NGS-based advances covering various genetic alterations (Microsatellite Instability, Single Nucleotide Variations, and Copy Number Variations), epigenetic changes (DNA methylation, histone modification, microRNAs) and differential gene expression during gastric tumorigenesis. We also briefly discuss the current and future potential biomarkers, drugs and therapeutic approaches available for the management of gastric cancer.

Ganglioneuroblastoma in a newborn with multiple metastases: a case report.

BACKGROUND: Ganglioneuroblastoma is a tumor of peripheral neuroblastic tissue which occurs predominantly in the pediatric age group; it is a rare occurrence in the newborn period with only one case reported at birth to date. CASE PRESENTATION: We report the case of a newborn male baby of Brahmin ethnicity from Nepal who presented with respiratory distress and blueberry muffin skin lesions after birth. A computed tomography scan showed a mass lesion in the posterior mediastinum, which was diagnosed as ganglioneuroblastoma on fine-needle aspiration cytology. He also had metastases to multiple sites including heart, lungs, skin and brain. CONCLUSIONS: Ganglioneuroblastoma is a rare tumor in newborns. Any newborn presenting with respiratory distress associated with blueberry muffin skin lesions should be evaluated for neuroblastic tumor.

Implication of microsatellite instability in human gastric cancers.

Microsatellite instability, one of the phenomena implicated in gastric cancer, is mainly associated with the expansion or contraction of microsatellite sequences due to replication errors caused most frequently by mutations in the mismatch repair (MMR) and tumour suppressor genes. Tumours exhibiting microsatellite instability are proven to have truncated products resulting from frequent mutations in mononucleotide or dinucleotide runs in coding and non-coding regions of the targeted genes. Epigenetic changes like hypermethylation of the promoter region of MMR genes as well as gene silencing are also responsible for the microsatellite instability phenotypes. Assessing microsatellite instability in tumours has proved to be an efficient tool for the prognosis of various cancers including colorectal and gastric cancers. Such tumours are characterized by distinct clinicopathological profiles. Biotic agents like Epstein Barr Virus and H. pylori along with other factors like family history, diet and geographical location also play an important role in the onset of gastric carcinogenesis. Instability of mitochondrial DNA has also been investigated and claimed to be involved in the occurrence of gastric cancers in humans. Development of simplified but robust and reproducible microsatellite instability based molecular tools promises efficient prognostic assessment of gastric tumours.

Early presentation of postintubation tracheoesophageal fistula: Perioperative anesthetic management.

Tracheoesophageal fistula (TEF) in adults occurs as a result of trauma, malignancy, cuff-induced tracheal necrosis from prolonged mechanical ventilation, traumatic endotracheal intubation, foreign body ingestion, prolonged presence of rigid nasogastric tube, and surgical complication. Anesthetic management for repair of TEF is a challenge. Challenges include difficulties in oxygenation or ventilation resulting from placement of endotracheal tube in or above the fistula; large fistula defect causing loss of tidal volume with subsequent gastric dilatation, atelactasis, and maintenance of one lung ventilation. The most common cause of acquired nonmalignant TEF is postintubation fistula, which develops after prolonged intubation for ventilatory support. Acquired TEF, which occurs after prolonged intubation, usually develops after 12-200 days of mechanical ventilation, with a mean of 42 days. We present a rare case of TEF that developed after 7 days of intubation. It was a difficult case to be diagnosed as patient had a history of polytrauma, followed by emergency intubation and both these conditions can contribute to tracheobronchial injury.

Isolation of good quality RNA from a medicinal plant seabuckthorn, rich in secondary metabolites.

Medicinal plants are being widely investigated owing to their ability to produce molecules of therapeutic significance. Isolation of good quality RNA is a tedious but primary step towards undertaking molecular biology experiments. However, medicinal plants are rich in secondary metabolites and not amenable to standard RNA isolation protocols involving Guanidine isothiocyanate (GITC). So an RNA isolation protocol from difficult samples (richer in secondary metabolites) is of highest desiderata. Here we propose a new protocol suitable for isolating RNA from plant tissues rich in secondary metabolites. To standard CTAB (Cetyl Trimethyl Ammonium Bromide) buffer, addition of 2% PVPP (polyvinyl polypyrrolidone) and 350 mM beta-mercaptoethanol was found useful. Use of glacial acetic acid (1M) along with ethanol for precipitation after phenolization and chloroform extraction enhanced the RNA yield. This is the first report of using glacial acetic acid in a CTAB based protocol for the precipitation of RNA. This protocol has been validated in medicinal plant Hippophae rhamnoides vern. seabuckthorn, where standard RNA isolation methods involving GITC and TRIZol extraction buffers failed. The RNA isolated by this method was of good quality as gauged by spectrophotometric readings and denaturing agarose gel electrophoresis. To the best of our knowledge, this RNA isolation protocol has never been published before. The RNA thus obtained could be suitably used for the downstream molecular procedures like Reverse Transcription Polymerase Chain Reaction (RT-PCR), Real Time-PCR, cDNA library construction, etc.

Contribution of germline BRCA1 and BRCA2 sequence alterations to breast cancer in Northern India.

BACKGROUND: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Indian women. We investigated the distribution and the nature of BRCA1 and BRCA2 germline mutations and polymorphisms in a cohort of 204 Indian breast cancer patients and 140 age-matched controls. METHOD: Cases were selected with regard to early onset disease (< or =40 years) and family history of breast and ovarian cancer. Two hundred four breast cancer cases along with 140 age-matched controls were analyzed for mutations. All coding regions and exon-intron boundaries of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis followed by direct sequencing of detected variants. RESULTS: In total, 18 genetic alterations were identified. Three deleterious frame-shift mutations (185delAG in exon 2; 4184del4 and 3596del4 in exon 11) were identified in BRCA1, along with one missense mutation (K1667R), one 5'UTR alteration (22C>G), three intronic variants (IVS10-12delG, IVS13+2T>C, IVS7+38T>C) and one silent substitution (5154C>T). Similarly three pathogenic protein-truncating mutations (6376insAA in exon 11, 8576insC in exon19, and 9999delA in exon 27) along with one missense mutation (A2951T), four intronic alterations (IVS2+90T>A, IVS7+75A>T, IVS8+56C>T, IVS25+58insG) and one silent substitution (1593A>G) were identified in BRCA2. Four previously reported polymorphisms (K1183R, S1613G, and M1652I in BRCA1, and 7470A>G in BRCA2) were detected in both controls and breast cancer patients. Rare BRCA1/2 sequence alterations were observed in 15 out of 105 (14.2%) early-onset cases without family history and 11.7% (4/34) breast cancer cases with family history. Of these, six were pathogenic protein truncating mutations. In addition, several variants of uncertain clinical significance were identified. Among these are two missense variants, one alteration of a consensus splice donor sequence, and a variant that potentially disrupts translational initiation. CONCLUSION: BRCA1 and BRCA2 mutations appear to account for a lower proportion of breast cancer patients at increased risk of harboring such mutations in Northern India (6/204, 2.9%) than has been reported in other populations. However, given the limited extent of reported family history among these patients, the observed mutation frequency is not dissimilar from that reported in other cohorts of early onset breast cancer patients. Several of the identified mutations are unique and novel to Indian patients.

High-throughput in planta expression screening identifies a class II ethylene-responsive element binding factor-like protein that regulates plant cell death and non-host resistance.

We performed high-throughput screening using the potato virus X (PVX) system to overexpress Nicotiana benthamiana genes in planta and identify positive regulators of cell death. This screening identified NbCD1, a novel class II ethylene-responsive element binding factor (ERF), as a potent inducer of the hypersensitive response (HR)-like cell death. NbCD1 expression was induced by treatments with INF1 elicitor and a non-host pathogen Pseudomonas cichorii. NbCD1 exhibited transcriptional repressor activity through its EAR motif, and this motif was necessary for NbCD1 to cause cell death. We identified 58 genes that displayed altered transcription following NbCD1 overexpression. NbCD1 overexpression downregulated the expression of HSR203, a negative regulator of hypersensitive death. Conditional expression of NbCD1 in Arabidopsis also caused cell death, indicating that NbCD1 downstream cascades are conserved in dicot plants. To further confirm the role of NbCD1 in defense, we used virus-induced gene silencing to demonstrate that NbCD1 is required for non-host resistance of N. benthamiana to the bacterial pathogen P. cichorii. Our data point to a model of transcriptional regulatory cascades. NbCD1 positively regulates cell death and contributes to non-host resistance, possibly by downregulating the expression of other defense response genes.