Deciphering tumour microenvironment and elucidating the origin of cancer cells in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (CCC) has an East Asian preponderance. It is associated with endometriosis, a benign condition where endometrial (inner lining of the uterus) tissue is found outside the uterus and on the peritoneal surface, in the abdominal or pelvic space. CCC is relatively more resistant to conventional chemotherapy compared to other ovarian cancer subtypes and is associated with a poorer prognosis. In this study, we recruited and obtained tumour tissues from seven patients across the four stages of CCC. The tumour and the tumour microenvironment (TME) from 7 CCC patients spanning clinical stages 1-4 were transcriptionally profiled using high-resolution scRNA-seq to gain insight into CCC's biological mechanisms. Firstly, we built a scRNA-seq resource for the CCC tumour microenvironment (TME). Secondly, we identified the different cell type proportions and found high levels of immune infiltration in CCC. Thirdly, since CCC is associated with endometriosis, we compared CCC with two publicly available endometriosis scRNA-seq datasets. The CCC malignant cells showed similarities with glandular secretory and ciliated epithelial cells found in endometriosis. Finally, we determined the differences in cell-cell communication between various cell types present in CCC TME and endometriosis conditions to gain insights into the transformations in CCC.

Clinical and Radiological Findings in Children with Anomalous Pontine Cranial Nerves.

We retrospectively reviewed the clinical and radiologic findings in 17 children with an aberrant cisternal CN7 and found that these patients had additional anomalies involving other pontine cranial nerves. The hallmark imaging feature identified in all patients was aberrant cisternal segment of an enlarged appearing CN7. The abnormal nerve coursed anteriorly towards the Gasserian ganglion where it fanned out towards the internal auditory canal, Meckel's cave or both. This finding was accompanied by a small cisternal CN5 which often had a lateral bowed appearance. CN5 and CN7 were abnormally close to each other. Meckel's cave appeared widened posteriorly and often was close to or merged with the internal auditory canal. Other abnormalities in the pontine cranial nerves included CN8 deficiency in the majority of children and variable CN6 deficiency. This constellation of findings was most often discovered in children having MR evaluation for sensorineural hearing loss and the majority of patients had preserved facial nerve function. In patients with available genetic testing, no pathogenic variants were observed. Interestingly, in 13 children with available birth history, 9 were notable for maternal or gestational diabetes (69%), suggesting a possible early intrauterine insult to the developing nerves.ABBREVIATIONS: CN= cranial nerve; OAVS= Oculo-Auriculo-Vertebral Spectrum; IAC= Internal Auditory Canal; PTCD= Pontine Tegmental Cap Dysplasia; EMR= Electronic Medical Record; SNHL= sensorineural hearing loss.

American Rhinologic Society Expert Practice Statement: Indications and Recommendations for Septoplasty in Children.

The goal of this American Rhinologic Society Expert Practice Statement (EPS) is to provide recommendations and guidance through evidence-based consensus statements regarding pediatric septoplasty. This EPS was developed following the previously published methodology and approval process. The topics of interest included appropriate indications, safety and efficacy, timing, relevant quality of life instruments, and surgical techniques. Following a modified Delphi approach, six statements were developed, five of which reached consensus and one that did not. These statements and accompanying evidence are summarized along with an assessment of future needs.

Enantioselective Synthesis of ß-l-5-[(E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) Uracil)] (l-BHDU) via Chiral Pure l-Dioxolane.

ß-l-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) uracil (l-BHDU, 17) is a potent and selective inhibitor of the varicella-zoster virus (VZV). l-BHDU (17) has demonstrated excellent anti-VZV activity and is a preclinical candidate to treat chickenpox, shingles (herpes zoster), and herpes simplex virus 1 (HSV-1) infections. Its monophosphate prodrug (POM-l-BHDU-MP, 24) demonstrated an enhanced pharmacokinetic and antiviral profile. POM-l-BHDU-MP (24), in vivo, effectively reduced the VZV viral load and was effective for the topical treatment of VZV and HSV-1 infections. Therefore, a viable synthetic procedure for developing POM-l-BHDU-MP (24) is needed. In this article, an efficient approach for the synthesis of l-BHDU (17) from a readily available starting material is described in 7 steps. An efficient and practical methodology for both chiral pure l- & d-dioxolane 11 and 13 were developed via diastereomeric chiral amine salt formation. Neutralization of the amine carboxylate salt of l-dioxolane 10 provides enantiomerically pure l-dioxane 11 (ee ≥ 99%). Optically pure 11 was utilized to construct the final nucleoside l-BHDU (17) and its monophosphate ester prodrug (POM-l-BHDU-MP, 24). Notably, the reported process eliminates expensive chiral chromatography for the synthesis of chiral pure l- & d-dioxolane, which offers avenues for the development and structure-activity relationship studies of l- & d-dioxolane-derived nucleosides.

Synthesis of Fluorinated Nucleosides/Nucleotides and Their Antiviral Properties.

The FDA has approved several drugs based on the fluorinated nucleoside pharmacophore, and numerous drugs are currently in clinical trials. Fluorine-containing nucleos(t)ides offer significant antiviral and anticancer activity. The insertion of a fluorine atom, either in the base or sugar of nucleos(t)ides, alters its electronic and steric parameters and transforms the lipophilicity, pharmacodynamic, and pharmacokinetic properties of these moieties. The fluorine atom restricts the oxidative metabolism of drugs and provides enzymatic metabolic stability towards the glycosidic bond of the nucleos(t)ide. The incorporation of fluorine also demonstrates additional hydrogen bonding interactions in receptors with enhanced biological profiles. The present article discusses the synthetic methodology and antiviral activities of FDA-approved drugs and ongoing fluoro-containing nucleos(t)ide drug candidates in clinical trials.

Process evaluation of a complex, multilevel, multicomponent scheme for the prevention and control of non-communicable diseases in Tamil Nadu, India: A mixed-methods protocol.

Background: Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality in India, necessitating development of multilevel and multicomponent interventions. Makkalai Thedi Maruthuvam (MTM) is a complex multilevel, multicomponent intervention developed and implemented by the south Indian State of Tamil Nadu. The scheme aims to deliver services for preventing and controlling diabetes, and hypertension at doorstep. This paper describes the protocol for planning and conducting the process evaluation of the MTM scheme. Methods and analysis: The process evaluation uses mixed methods (secondary data analysis, key informant interviews, in-depth interviews, conceptual content analysis of documents, facility-based survey and non-participant observation) to evaluate the implementation of the MTM scheme. The broad evaluation questions addressed the fidelity, contexts, mechanisms of impact and challenges encountered by the scheme using the Consolidated Framework for Implementation Research (CFIR) framework. The specific evaluation questions addressed selected inputs and processes identified as critical to implementation by the stakeholders. The CFIR framework will guide the thematic analysis of the qualitative interviews to explore the adaptations and deviations introduced during implementation in various contexts. The quantitative data on the indicators developed for the specific evaluation questions will be cleaned and descriptively analysed.

Evaluation of the cytotoxic activity of sorafenib-loaded camel milk casein nanoparticles against hepatocarcinoma cells.

Sorafenib, a multikinase inhibitor is used to treat hepatocellular and renal carcinoma. However, a low solubility impedes its bioavailability and thus, effectiveness. This study aims to enhance its effectiveness by using novel camel milk casein nanoparticles as a delivery system. This study evaluates the cytotoxicity of sorafenib encapsulated in camel milk casein nanoparticles against human hepatocarcinoma cells (HepG2 cells) in vitro. Optimal drug loaded nanoparticles were stable for 1 month, had encapsulation efficiency of 96%, exhibited a particle size of 230 nm, zeta potential of -14.4 and poly disparity index of 0.261. Treatment with it led to cell morphology and DNA fragmentation as a characteristic of apoptosis. Flow cytometry showed G1 phase arrest of cell cycle and 26% increased apoptotic cells population upon treatment as compared to control. Sorafenib-loaded casein nanoparticles showed 6-fold increased ROS production in HepG2 cells as compared to 4-fold increase shown by the free drug. Gene and protein expression studies done by qPCR and western blotting depicted upregulation of tumor suppressor gene p53, pro-apoptotic Bax, and caspase-3 along with downregulated anti-apoptotic Bcl-2 gene and protein expression which further emphasized death by apoptosis. It is concluded regarding the feasibility of these casein nanoparticles as a delivery system with enhanced therapeutic outcomes against hepatocellular carcinoma cells.

fMRI BOLD responses to film stimuli and their association with exhaled nitric oxide in asthma and health.

Little is known about central nervous system (CNS) responses to emotional stimuli in asthma. Nitric oxide in exhaled breath (FENO) is elevated in asthma due to allergic immune processes, but endogenous nitric oxide is also known to modulate CNS activity. We measured fMRI blood oxygen-dependent (BOLD) brain activation to negative (blood-injection-injury themes) and neutral films in 31 participants (15 with asthma). Regions-of-interest analysis was performed on key areas relevant to central adaptive control, threat processing, or salience networks, with dorsolateral prefrontal cortex (PFC), anterior insula, dorsal anterior cingulate cortex (dACC), amygdala, ventral striatum, ventral tegmentum, and periaqueductal gray, as well as top-down modulation of emotion, with ventrolateral and ventromedial PFC. Both groups showed less BOLD deactivation from fixation cross-baseline in the left anterior insula and bilateral ventromedial PFC for negative than neutral films, and for an additional number of areas, including the fusiform gyrus, for film versus recovery phases. Less deactivation during films followed by less recovery from deactivation was found in asthma compared to healthy controls. Changes in PCO2 did not explain these findings. FENO was positively related to BOLD activation in general, but more pronounced in healthy controls and more likely in neutral film processing. Thus, asthma is associated with altered processing of film stimuli across brain regions not limited to central adaptive control, threat processing, or salience networks. Higher levels of NO appear to facilitate CNS activity, but only in healthy controls, possibly due to allergy's masking effects on FENO.

Dataset from transcriptome profiling of Musa resistant and susceptible cultivars in response to Fusarium oxysporum f.sp. cubense race1 and TR4 challenges using Illumina NovaSeq.

In this investigation, the study focused on the RNAseq data generated in response to Fusarium oxysporum f.sp. cubense (Foc) race1 (Cavendish infecting strain VCG 0124), targeting both resistant (cv. Rose, AA) and susceptible cultivars (Namarai, AA), and Tropical Race 4 (TR4, strain VCG 01213/16), involving resistant (cv. Rose, AA) and susceptible cultivars (Matti, AA). The respective contrasting cultivars were independently challenged with Foc race1 and TR4, and the root and corm samples were collected in two replications at varying time intervals [0th (control), 2nd, 4th, 6th, and 8th days] in duplicates. The RNA samples underwent stringent quality checks, with all 80 samples meeting the primary parameters, including a satisfactory RNA integrity number (>7). Subsequent library preparation and secondary quality control steps were executed successfully for all samples, paving the way for the sequencing phase. Sequencing generated an extensive amount of data, yielding a range of 10 to 31 million paired-end raw reads per sample, resulting in a cumulative raw data size of 11-50 GB. These raw reads were aligned against the reference genome of Musa acuminata ssp. malaccensis version 2 (DH Pahang), as well as the pathogen genomes of Foc race 1 and Foc TR4, using the HISAT2 alignment tool. The focal point of this study was the investigation of differential gene expression patterns of Musa spp. upon Foc infection. In Foc race1 resistant and susceptible root samples across the designated day intervals, a significant number of genes displayed up-regulation (ranging from 1 to 228) and down-regulation (ranging from 1 to 274). In corm samples, the up-regulated genes ranged from 1 to 149, while down-regulated genes spanned from 3 to 845. For Foc TR4 resistant and susceptible root samples, the expression profiles exhibited a notable up-regulation of genes (ranging from 31 to 964), along with a down-regulation range of 316-1315. In corm samples, up-regulated genes ranged from 57 to 929, while down-regulated genes were observed in the range of 40-936. In addition to the primary analysis, a comprehensive secondary analysis was conducted, including Gene Ontology (GO), euKaryotic Orthologous Groups (KOG) classification, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and investigations into Simple Sequence Repeats (SSRs), Single Nucleotide Polymorphisms (SNPs), and microRNA (miRNA). The complete dataset was carefully curated and housed at ICAR-NRCB, Trichy, ensuring its accuracy and accessibility for the duration of the study. Further, the raw transcriptome read datasets have been successfully submitted to the National Center for Biotechnology Information - Sequence Read Archive (NCBI-SRA) database, ensuring the accessibility and reproducibility of this valuable dataset for further research endeavors.

The impact of radio-chemotherapy on tumour cells interaction with optimal control and sensitivity analysis.

Oncologists and applied mathematicians are interested in understanding the dynamics of cancer-immune interactions, mainly due to the unpredictable nature of tumour cell proliferation. In this regard, mathematical modelling offers a promising approach to comprehend this potentially harmful aspect of cancer biology. This paper presents a novel dynamical model that incorporates the interactions between tumour cells, healthy tissue cells, and immune-stimulated cells when subjected to simultaneous chemotherapy and radiotherapy for treatment. We analysed the equilibria and investigated their local stability behaviour. We also study transcritical, saddle-node, and Hopf bifurcations analytically and numerically. We derive the stability and direction conditions for periodic solutions. We identify conditions that lead to chaotic dynamics and rigorously demonstrate the existence of chaos. Furthermore, we formulated an optimal control problem that describes the dynamics of tumour-immune interactions, considering treatments such as radiotherapy and chemotherapy as control parameters. Our goal is to utilize optimal control theory to reduce the cost of radiotherapy and chemotherapy, minimize the harmful effects of medications on the body, and mitigate the burden of cancer cells by maintaining a sufficient population of healthy cells. Cost-effectiveness analysis is employed to identify the most economical strategy for reducing the disease burden. Additionally, we conduct a Latin hypercube sampling-based uncertainty analysis to observe the impact of parameter uncertainties on tumour growth, followed by a sensitivity analysis. Numerical simulations are presented to elucidate how dynamic behaviour of model is influenced by changes in system parameters. The numerical results validate the analytical findings and illustrate that a multi-therapeutic treatment plan can effectively reduce tumour burden within a given time frame of therapeutic intervention.

Screening for protein energy wasting in children with chronic kidney disease using dual energy x-ray absorptiometry as an additional tool.

BACKGROUND: The current diagnosis of protein energy wasting (PEW) is based on scoring systems that lack precision in measuring muscle deficits. We undertook this cross-sectional study to determine the prevalence of PEW in children with chronic kidney disease (CKD) using a scoring system that included dual energy x-ray absorptiometry (DEXA) for measuring lean body mass (LBM) and to determine the prevalence of selected markers in PEW. METHODS: Thirty CKD and 20 healthy children (1-18 years) were evaluated for (1) reduced dietary protein intake (DPI); (2) BMI < fifth centile for height age (BMI/HA); (3) serum albumin < 3.8 g/dl, cholesterol < 100 mg/dl, or CRP > 3 mg/L; (4) LBM < fifth centile for height age [LBMr] on DEXA. PEW was scored as minimal-one parameter positive in 2/4 categories; standard-one parameter positive in 3/4 categories; or modified-standard plus height < 2 SD. RESULTS: Twenty children with CKD (66.7%) had PEW, (5/9) 55% in CKD 3, and (15/21) 71% in advanced CKD; minimal 12, standard 1, and modified 7. LBMr was seen in 20 (100%), reduced DPI in 16 (80%), and BMI/HA in 6 (30%) children with PEW. LBMr had 100% sensitivity and BMI/HA 100% specificity. LBMr was seen in 8 who had no other criteria for PEW. None of the parameters were positive in controls (p < 0.01). CONCLUSIONS: PEW prevalence in CKD was high. Both prevalence and severity were higher in advanced CKD. LBMr was a highly sensitive marker to detect PEW. LBMr seen in some children with CKD who were negative for other markers could represent subclinical PEW.

Molecular characterization of Red banana and its somaclonal variant: a comprehensive study.

The prized Red banana, selected for superior qualities, demands strong genetic uniformity for successful clonal propagation and preservation. Ensuring this uniformity early in the growth of in vitro Red banana plants is essential, as gene mutations and chromosome rearrangements during tissue culture can jeopardize both cloning and germplasm conservation. In this situation, molecular markers play a pivotal role in confirming genetic stability. Thus the study aims to discover a marker that identifies tissue-cultured Red bananas from their virescent variants during initial sub-culturing. A marker linked to anthocyanin has been identified which effectively differentiated Red bananas from virescent variants and it was further validated in various banana cultivars, ornamental Musa species and their interspecific hybrids. The PCR-based marker showed remarkable specificity, discerning Red bananas from virescent variants during tissue culture. It also distinguished green and red offspring, cutting time and resource costs, and shortening the banana breeding cycle. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03868-6.

Arctic weather variability and connectivity.

The Arctic's rapid sea ice decline may influence global weather patterns, making the understanding of Arctic weather variability (WV) vital for accurate weather forecasting and analyzing extreme weather events. Quantifying this WV and its impacts under human-induced climate change remains a challenge. Here we develop a complexity-based approach and discover a strong statistical correlation between intraseasonal WV in the Arctic and the Arctic Oscillation. Our findings highlight an increased variability in daily Arctic sea ice, attributed to its decline accelerated by global warming. This weather instability can influence broader regional patterns via atmospheric teleconnections, elevating risks to human activities and weather forecast predictability. Our analyses reveal these teleconnections and a positive feedback loop between Arctic and global weather instabilities, offering insights into how Arctic changes affect global weather. This framework bridges complexity science, Arctic WV, and its widespread implications.

Rhino orbital cerebral mucormycosis in settings of COVID-19 infection: A case series of thirteen patients.

Rhino orbital cerebral mucormycosis (ROCM) is an important infectious disease encountered in large numbers in this recent post-COVID-19 era. An alteration in the defense immune system during COVID-19 illness; in the presence of uncontrolled hyperglycemia has led to the new epidemic of ROCM, especially in developing nations such as India. This case series of thirteen patients illustrates the various clinical presentations, laboratory parameters, imaging features and outcomes of patients with ROCM admitted to a tertiary care hospital in Northern India. In our case series, a total of 13 newly diagnosed cases of rhino-orbital-cerebral mucormycosis were studied. A history of COVID-19 illness was observed in seven cases (53.8%) with a mean duration of mucormycosis after 25 ± 3.6 days, the use of steroids during COVID-19 illness was seen in 5 cases (38.5%), and oxygen therapy was given in 4 cases (30.8%). A comorbid state in the form of diabetes mellitus was present in 12 cases (92.3%) with a mean duration of 16.69 months, with an important finding of seven cases (53.85%) having new-onset diabetes; hypertension was present in three cases (23.1%). Magnetic resonance imaging of paranasal sinuses showed involvement of multiple sinuses in all 13 cases (100%), including maxillary and ethmoidal sinuses, with frontal involvement in 12 cases (92.3%), sphenoidal involvement in 11 cases (84.6%), symmetric involvement in 9 cases (69.2%), mastoiditis in four cases (30.8%), maxillary space involvement in four cases (30.8%), and palatal involvement in one case (7.7%). On statistical analysis, there was a significant association of new-onset diabetes, optic neuropathy and high C reactive protein with blindness (P-value < 0.05) in our study. However, there were no statistically significant association for the involvement of nervous system in our study. Multispecialty approach treatment was given in the liposomal amphotericin B therapy in all the patients along with thorough endo-nasal debridement done in all cases, transcutaneous retrobulbar amphotericin B in six cases (46.2%) with exenteration done in seven patients (53.9%). At 3 months of follow-up, there was substantial clinical improvement in all cases. There should be definite emphasis on high suspicion of mucor clinically for early diagnosis and aggressive management at the initial state of diagnosis for better outcomes. The need for sustained proper glycemic control during the COVID-19 era along with judicious use of steroids and public awareness of early symptoms and manifestations of mucor can curb the magnitude of such potentially opportunistic epidemics to a substantial rate. New-onset diabetes mellitus, optic neuropathy and high C reactive protein (>50 mg/L) showed statistically significant association with blindness. The longer the infection remains undetected, the greater the devastation ROCM can impose, of which blindness is an important hazard.

Missed injuries associated with maxillofacial trauma.

Background: Maxillofacial trauma in polytrauma settings is often associated with multiple injuries both trivial and life threatening, and their timely detection is the mainstay of definitive trauma management for preventing mortality and morbidity. Emergency management of all the patients reporting to our maxillofacial unit is either done by our center or they have been managed at the peripheral health care facility and relatively stable patient is referred to us. Anecdotally, we found inadequacies in transport methods, diagnosis, and detection of associated injuries in the patients referred to us from the peripheral health care facility. To substantiate our finding, this observational study has been planned. Objective: To identify, diagnose, and document missed injuries associated with the maxillofacial trauma. Materials and Methods: All the trauma patients referred to the maxillofacial unit directly from the peripheral health care facility during the period of October 2017 to March 2019 were included in this study. Results: We observed a total of 270 patients having both pure maxillofacial trauma and patients having documented other injuries associated with maxillofacial injuries. In our maxillofacial unit, functioning as a secondary screen, head to toe clinical examination was performed to document any previously missed out injuries. Missed injuries diagnosed by us included spinal injuries, temporal bone fractures, fractures of the styloid process, and even head injury. Conclusion: Frequent reassessment of trauma patients at all levels of trauma care and training health care personnel particularly those at peripheral health care facility and those involved in prehospital care are pivotal in managing the trauma patients in most efficient manner.

Management and outcome of locally advanced oral squamous cell carcinoma.

Management of locally advanced OSCC is multimodal. No single therapy has been proved to be efficacious. However there is a trend towards surgical intervention in operable disease. In this review we appraise the various therapies used for the management of locally advanced OSCC. We review the literature with regards to the various treatment options for locally advanced OSCC. We categorically divided the manuscript into resectable, unresectable and technically unresectable disease. Surgery is the ideal treatment modality for resectable disease. For unresectable disease concurrent chemoradiation appears to improve survival compared to radiotherapy alone. Induction therapy might downstage tumors in the unresectable category. Targeted and Immunotherapy is reserved for recurrent, metastatic or platinum refractory OSCC. Management of locally advanced OSCC is multimodal with surgery playing the primary role. In the event where the tumor is in operable concurrent chemoradiotherapy is regarded as the best treatment modality. Induction chemotherapy currently cannot be recommended for resectable or even unresectable oral squamous cell carcinomas. However for technically unresectable disease it might play a role in improving respectability but it depends on the response of the tumor. Targeted therapy and immunotherapy is currently used for recurrent, metastatic and/or platinum refractory Head and Neck cancers. Currently it is not recommended for initial management of locally advanced disease.

Fluctuating Atlantic inflows modulate Arctic atlantification.

Enhanced warm, salty subarctic inflows drive high-latitude atlantification, which weakens oceanic stratification, amplifies heat fluxes, and reduces sea ice. In this work, we show that the atmospheric Arctic Dipole (AD) associated with anticyclonic winds over North America and cyclonic winds over Eurasia modulates inflows from the North Atlantic across the Nordic Seas. The alternating AD phases create a "switchgear mechanism." From 2007 to 2021, this switchgear mechanism weakened northward inflows and enhanced sea-ice export across Fram Strait and increased inflows throughout the Barents Sea. By favoring stronger Arctic Ocean circulation, transferring freshwater into the Amerasian Basin, boosting stratification, and lowering oceanic heat fluxes there after 2007, AD+ contributed to slowing sea-ice loss. A transition to an AD- phase may accelerate the Arctic sea-ice decline, which would further change the Arctic climate system.

Rare disease variant curation from literature: assessing gaps with creatine transport deficiency in focus.

BACKGROUND: Approximately 4-8% of the world suffers from a rare disease. Rare diseases are often difficult to diagnose, and many do not have approved therapies. Genetic sequencing has the potential to shorten the current diagnostic process, increase mechanistic understanding, and facilitate research on therapeutic approaches but is limited by the difficulty of novel variant pathogenicity interpretation and the communication of known causative variants. It is unknown how many published rare disease variants are currently accessible in the public domain. RESULTS: This study investigated the translation of knowledge of variants reported in published manuscripts to publicly accessible variant databases. Variants, symptoms, biochemical assay results, and protein function from literature on the SLC6A8 gene associated with X-linked Creatine Transporter Deficiency (CTD) were curated and reported as a highly annotated dataset of variants with clinical context and functional details. Variants were harmonized, their availability in existing variant databases was analyzed and pathogenicity assignments were compared with impact algorithm predictions. 24% of the pathogenic variants found in PubMed articles were not captured in any database used in this analysis while only 65% of the published variants received an accurate pathogenicity prediction from at least one impact prediction algorithm. CONCLUSIONS: Despite being published in the literature, pathogenicity data on patient variants may remain inaccessible for genetic diagnosis, therapeutic target identification, mechanistic understanding, or hypothesis generation. Clinical and functional details presented in the literature are important to make pathogenicity assessments. Impact predictions remain imperfect but are improving, especially for single nucleotide exonic variants, however such predictions are less accurate or unavailable for intronic and multi-nucleotide variants. Developing text mining workflows that use natural language processing for identifying diseases, genes and variants, along with impact prediction algorithms and integrating with details on clinical phenotypes and functional assessments might be a promising approach to scale literature mining of variants and assigning correct pathogenicity. The curated variants list created by this effort includes context details to improve any such efforts on variant curation for rare diseases.

ABERRANT EXPRESSION OF COL14A1, CELRS3, and CTHRC1 IN BREAST CANCER СELLS.

BACKGROUND: Collagens, which are the major components of the extracellular matrix involved in the regulation of tumor microenvironment, could be differentially expressed in breast cancer (BC) with different transcriptome profiling. AIM: To analyze the transcript level expression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, COL14A1, CTHRC1, and CELRS3 genes and the clinical relevance of their differential expression in BC. MATERIALS AND METHODS: The transcript level expression of the genes was analyzed using the quantitative real-time PCR (qPCR) in tumor tissue of 60 BC patients. RESULTS: Overexpression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, CTHRC, and CELRS3 anddown-regulated expression of COL14A1 were observed. COL14A1 down-regulation was associated with aggressive, basal, and Her-2/neu BC subtypes (p = 0.031). Overexpression of CELSR3 was found to be associated with the older age of the patients (> 55 years, p = 0.049). Further analysis with the TCGA BC data set has shown a concordance in the differential expression of the above genes. Furthermore, overexpression of CTHRC1 was associated with poor overall survival (OS), particularly with poor prognosis (p = 0.00042) for the luminal BC subtype. On the other hand, CELSR3 overexpression was associated with mucinous tumors and poor prognosis in post-menopausal women. In silicotarget prediction identified several BC-associated miRNAs and members of miR-154, -515, and -10 families to perform a likely regulatory role in the above ECM genes. CONCLUSION: The present study shows that the expression of COL14A1 and CTHRC1 may serve as potential biological markers for the detection of basal BC and the prognosis of survival for patients with the luminal subtype of BC.

Study of Hemato-morphological Features in Neuroblastoma Infiltrating Marrow.

Objective Neuroblastoma typically affects children within the first 5 years of life and accounts for 10% of all pediatric malignancies. Neuroblastoma at onset may manifest as a localized or metastatic illness. The aim of this study was to identify hematomorphological features in neuroblastoma infiltrating marrow as well as to ascertain the prevalence of bone marrow infiltration in neuroblastoma. Materials and Methods This retrospective study included newly diagnosed 79 cases of neuroblastoma, which were referred for bone marrow examination for the staging of the disease. Medical records were retrieved to acquire hematomorphological findings of peripheral blood and bone marrow smears. Statistical Package for Social Sciences, IBM Inc., USA, version 21.0 was used to analyze the data. Results The interquartile age range of neuroblastoma cases was 24.0 to 72.0 months (median = 48 months) with a male to female ratio of 2.7:1. Also, 55.6% (44/79) of cases in the study population showed evidence of marrow infiltration. The bone marrow infiltration was significantly linked to thrombocytopenia ( p = 0.043) and nucleated red blood cells ( p = 0.003) in peripheral blood. The bone marrow smears of cases with infiltration showed a significant shift to the left in the myeloid series ( p = 0.001) and an increased number of erythroid cells ( p = 0.001). Conclusion For neuroblastoma patients, a diligent, exhaustive search for infiltrating cells in bone marrow is advised if thrombocytopenia or nucleated red blood cells are identified on a peripheral blood smear and bone marrow smears showed myeloid left shift with an increased number of erythroid cells.