Benign breast tumors may arise on different immunological backgrounds.

Benign breast tumors are a nonthreatening condition defined as abnormal cell growth within the breast without the ability to invade nearby tissue. However, benign lesions hold valuable biological information that can lead us toward better understanding of tumor biology. In this study, we have used two pathway analysis algorithms, Pathifier and gene set variation analysis (GSVA), to identify biological differences between normal breast tissue, benign tumors and malignant tumors in our clinical dataset. Our results revealed that one-third of all pathways that were significantly different between benign and malignant tumors were immune-related pathways, and 227 of them were validated by both methods and in the METABRIC dataset. Furthermore, five of these pathways (all including genes involved in cytokine and interferon signaling) were related to overall survival in cancer patients in both datasets. The cellular moieties that contribute to immune differences in malignant and benign tumors were analyzed using the deconvolution tool, CIBERSORT. The results showed that levels of some immune cells were specifically higher in benign than in malignant tumors, and this was especially the case for resting dendritic cells and follicular T-helper cells. Understanding the distinct immune profiles of benign and malignant breast tumors may aid in developing noninvasive diagnostic methods to differentiate between them in the future.

Transcriptome profiling of lumpfish (Cyclopterus lumpus) head kidney to Renibacterium salmoninarum at early and chronic infection stages.

Renibacterium salmoninarum causes Bacterial Kidney Disease (BKD) in several fish species. Atlantic lumpfish, a cleaner fish, is susceptible to R. salmoninarum. To profile the transcriptome response of lumpfish to R. salmoninarum at early and chronic infection stages, fish were intraperitoneally injected with either a high dose of R. salmoninarum (1 × 109 cells dose-1) or PBS (control). Head kidney tissue samples were collected at 28- and 98-days post-infection (dpi) for RNA sequencing. Transcriptomic profiling identified 1971 and 139 differentially expressed genes (DEGs) in infected compared with control samples at 28 and 98 dpi, respectively. At 28 dpi, R. salmoninarum-induced genes (n = 434) mainly involved in innate and adaptive immune response-related pathways, whereas R. salmoninarum-suppressed genes (n = 1537) were largely connected to amino acid metabolism and cellular processes. Cell-mediated immunity-related genes showed dysregulation at 98 dpi. Several immune-signalling pathways were dysregulated in response to R. salmoninarum, including apoptosis, alternative complement, JAK-STAT signalling, and MHC-I dependent pathways. In summary, R. salmoninarum causes immune suppression at early infection, whereas lumpfish induce a cell-mediated immune response at chronic infection. This study provides a complete depiction of diverse immune mechanisms dysregulated by R. salmoninarum in lumpfish and opens new avenues to develop immune prophylactic tools to prevent BKD.

Impact of an Educational Measure on the Quality of Medical Certificate of Cause of Death at a Tertiary Care Teaching Hospital: A Pre-post Interventional Study.

Background A death certificate is an important document that serves as a tool for gathering epidemiological data and as an essential legal document. Although it is a mandatory document to be given for all deaths, the quality of its filling is often an ignored aspect and errors are frequently encountered. This documentation process can be mastered with minimal educational efforts. This study aimed to determine the utility of an educational measure in improving the accuracy of death certificate documentation. Methods and materials This pre- and post-interventional study was conducted at Maharaja Agrasen Medical College, Agroha, a tertiary care teaching hospital in Hisar, Haryana, India, wherein an audit of death certificates was done before and after an educational intervention on doctors responsible for filling death certificates. Errors in the death certificates were classified into major and minor errors and compared in the pre- and post-intervention groups. Results A total of 184 pre-intervention and 136 post-intervention death certificates were audited. In the pre-intervention certificates, at least one major and one minor error were present in 88% and 92.93% of the certificates, respectively, which was reduced to 33% (p < 0.01; relative risk (RR) = 3.62; 95% confidence interval (CI) = 2.69-4.91) and 38% (p < 0.01; RR = 3.33; 95% CI = 2.53-4.37), respectively, post-intervention. Reduction in all types of major and minor errors was statistically significant (p < 0.05). Conclusions Errors in death certification are a common but frequently ignored problem that can have a negative impact on epidemiological data and can be drastically reduced with simple educational measures, which need to be carried out regularly.

Clinico-epidemiological presentations and management of Nipah virus infection during the outbreak in Kozhikode district, Kerala state, India 2023.

India experienced its sixth Nipah virus (NiV) outbreak in September 2023 in the Kozhikode district of Kerala state. The NiV is primarily transmitted by spillover events from infected bats followed by human-to-human transmission. The clinical specimens were screened using real-time RT-PCR, and positive specimens were further characterized using next-generation sequencing. We describe here an in-depth clinical presentation and management of NiV-confirmed cases and outbreak containment activities. The current outbreak reported a total of six cases with two deaths, with a case fatality ratio of 33.33%. The cases had a mixed presentation of acute respiratory distress syndrome and encephalitis syndrome. Fever was a persistent presentation in all the cases. The Nipah viral RNA was detected in clinical specimens until the post-onset day of illness (POD) 14, with viral load in the range of 1.7-3.3 × 104 viral RNA copies/mL. The genomic analysis showed that the sequences from the current outbreak clustered into the Indian clade similar to the 2018 and 2019 outbreaks. This study highlights the vigilance of the health system to detect and effectively manage the clustering of cases with clinical presentations similar to NiV, which led to early detection and containment activities.

GPCR-IPL score: multilevel featurization of GPCR-ligand interaction patterns and prediction of ligand functions from selectivity to biased activation.

G-protein-coupled receptors (GPCRs) mediate diverse cell signaling cascades after recognizing extracellular ligands. Despite the successful history of known GPCR drugs, a lack of mechanistic insight into GPCR challenges both the deorphanization of some GPCRs and optimization of the structure-activity relationship of their ligands. Notably, replacing a small substituent on a GPCR ligand can significantly alter extracellular GPCR-ligand interaction patterns and motion of transmembrane helices in turn to occur post-binding events of the ligand. In this study, we designed 3D multilevel features to describe the extracellular interaction patterns. Subsequently, these 3D features were utilized to predict the post-binding events that result from conformational dynamics from the extracellular to intracellular areas. To understand the adaptability of GPCR ligands, we collected the conformational information of flexible residues during binding and performed molecular featurization on a broad range of GPCR-ligand complexes. As a result, we developed GPCR-ligand interaction patterns, binding pockets, and ligand features as score (GPCR-IPL score) for predicting the functional selectivity of GPCR ligands (agonism versus antagonism), using the multilevel features of (1) zoomed-out 'residue level' (for flexible transmembrane helices of GPCRs), (2) zoomed-in 'pocket level' (for sophisticated mode of action) and (3) 'atom level' (for the conformational adaptability of GPCR ligands). GPCR-IPL score demonstrated reliable performance, achieving area under the receiver operating characteristic of 0.938 and area under the precision-recall curve of 0.907 (available in gpcr-ipl-score.onrender.com). Furthermore, we used the molecular features to predict the biased activation of downstream signaling (Gi/o, Gq/11, Gs and ß-arrestin) as well as the functional selectivity. The resulting models are interpreted and applied to out-of-set validation with three scenarios including the identification of a new MRGPRX antagonist.

Climate change can impair bacterial pathogen defences in sablefish via hypoxia-mediated effects on adaptive immunity.

Low-oxygen levels (hypoxia) in aquatic habitats are becoming more common because of global warming and eutrophication. However, the effects on the health/disease status of fishes, the world's largest group of vertebrates, are unclear. Therefore, we assessed how long-term hypoxia affected the immune function of sablefish, an ecologically and economically important North Pacific species, including the response to a formalin-killed Aeromonas salmonicida bacterin. Sablefish were held at normoxia or hypoxia (100% or 40% air saturated seawater, respectively) for 6-16 weeks, while we measured a diverse array of immunological traits. Given that the sablefish is a non-model organism, this involved the development of a species-specific methodological toolbox comprised of qPCR primers for 16 key immune genes, assays for blood antibacterial defences, the assessment of blood immunoglobulin (IgM) levels with ELISA, and flow cytometry and confocal microscopy techniques. We show that innate immune parameters were typically elevated in response to the bacterial antigens, but were not substantially affected by hypoxia. In contrast, hypoxia completely prevented the ∼1.5-fold increase in blood IgM level that was observed under normoxic conditions following bacterin exposure, implying a serious impairment of adaptive immunity. Since the sablefish is naturally hypoxia tolerant, our results demonstrate that climate change-related deoxygenation may be a serious threat to the immune competency of fishes.

Squamous cell carcinoma of skin in a case of post-filariasis chronic lower limb lymphedema- a case study and review of literature.

INTRODUCTION AND IMPORTANCE: Filariasis, predominantly caused by the parasite Wuchereria Bancrofti, is a key etiological factor in lymphedema development. Lymphedema, characterized by persistent lymphatic obstruction, leads to significant changes in immunological factors and protein composition. These alterations play a crucial role in the delayed diagnosis of squamous cell carcinoma within chronic lymphedema contexts. Notably, chronic lymphedema is an infrequent but significant precursor to squamous cell carcinoma, with fewer than 20 cases reported in medical literature, including only 11 cases affecting the lower limbs. The management of squamous cell carcinoma in lymphedema is challenging due to the rarity of cases and the resulting lack of experience among clinicians. CASE PRESENTATION: The report focuses on a 69-year-old woman with long-standing right lower limb lymphedema following filariasis. She underwent treatment for a non-healing ulcer in the right gluteal region, diagnosed as moderately differentiated squamous cell carcinoma. Following a wide local excision with primary closure, her lower limb swelling persisted, and subsequent diagnosis confirmed regional lymph node metastasis. The patient was then considered for immunotherapy. CLINICAL DISCUSSION: This case emphasizes the link between chronic lymphedema and squamous cell carcinoma. It highlights the necessity for a multidisciplinary approach for timely and effective treatment, addressing the rarity and complexity of such cases. CONCLUSION: The successful application of immunotherapy in this case illustrates a favorable clinical outcome, marking a significant advancement in treating similar conditions. This finding contributes to the evolving knowledge in this medical field, suggesting immunotherapy as a promising treatment option. METHODS: This case report meticulously follows the SCARE 2023 guidelines: updating consensus Surgical Case Report guidelines (Sohrabi et al., 2023) [1]. These guidelines ensure high-quality reporting in surgical case reports. The report details the evaluation, diagnosis, and a comprehensive review of the literature pertaining to a patient with squamous cell carcinoma of the skin and regional nodal metastasis, which developed in the context of post-filariasis chronic lower limb lymphedema. By employing a multidisciplinary approach, this report achieves a thorough and standardized presentation of the case, serving as a benchmark and an additional tool for raising awareness about such rare medical conditions.

Nutritional Status of Underprivileged Indian Children and Youth with Type-1 Diabetes - A Multicentre Study.

Background: India has the highest number of prevalent type-1 diabetes (T1D) cases in the under-20-year age population. Data on the anthropometry of underprivileged Indian children with T1D are scarce. In economically disadvantaged countries like India, poor growth in patients with T1D is a major concern due to limited accessibility and affordability. Besides, due to the double burden of malnutrition, the prevalence of obesity is increasing mirroring the global trends, which may lead to the development of insulin resistance. Objectives: This study aims to assess the prevalence of malnutrition in Indian children and youth with T1D and to identify the determinants of short stature. Methods: A registry-based cross-sectional analysis of data collected from various centres across India enrolled in the Changing Diabetes in Children (CDiC) programme. Results: We observed that 6.4% were undernourished (3.4% severe undernutrition) and 17.7% (overweight 13.2%) had combined overweight/obesity. 21.2% of participants had short stature (adjusted for mid-parental height) with 7.4% cases of familial short stature. Longer duration of illness and insulin requirement were significant positive predictors of short stature while glycaemic control, insulin regimen and mid-parental height did not have a significant relationship with short stature. Participants on basal-bolus regimen had significantly higher insulin requirements and better glycaemic control than the ones on mixed-split regimen. Conclusion: We report that around one-fifth of children and youth with T1D were overweight/obese and around a fourth were stunted, especially those with longer duration of diabetes and higher insulin requirements. Close monitoring of anthropometric parameters is necessary for all children with T1D to optimize growth and nutrition.

Advancing prostate cancer detection: a comparative analysis of PCLDA-SVM and PCLDA-KNN classifiers for enhanced diagnostic accuracy.

This investigation aimed to assess the effectiveness of different classification models in diagnosing prostate cancer using a screening dataset obtained from the National Cancer Institute's Cancer Data Access System. The dataset was first reduced using the PCLDA method, which combines Principal Component Analysis and Linear Discriminant Analysis. Two classifiers, Support Vector Machine (SVM) and k-Nearest Neighbour (KNN), were then applied to compare their performance. The results showed that the PCLDA-SVM model achieved an impressive accuracy rate of 97.99%, with a precision of 0.92, sensitivity of 92.83%, specificity of 97.65%, and F1 score of 0.93. Additionally, it demonstrated a low error rate of 0.016 and a Matthews Correlation Coefficient (MCC) and Kappa coefficient of 0.946. On the other hand, the PCLDA-KNN model also performed well, achieving an accuracy of 97.8%, precision of 0.93, sensitivity of 93.39%, specificity of 97.86%, an F1 score of 0.92, a high MCC and Kappa coefficient of 0.98, and an error rate of 0.006. In conclusion, the PCLDA-SVM method exhibited improved efficacy in diagnosing prostate cancer compared to the PCLDA-KNN model. Both models, however, showed promising results, suggesting the potential of these classifiers in prostate cancer diagnosis.

Genomic Characterization of Mosquito Isolates of Chikungunya Virus (Outbreak Strains 2022) Using Next-Generation Sequencing.

Background: A massive outbreak of dengue-like illness was reported from Pune district of Maharashtra, India during May-June 2022. Isolation and characterization of the etiological agent at genomic level for possible mutations that led to higher transmissibility is the topic of the study. Methods: Entomological investigations were carried out by ICMR-National Institute of Virology (Pune, India); Aedes aegypti mosquitoes were collected and processed for virus detection by molecular techniques. Positive mosquito pools were processed for virus isolation in cell culture. Sanger sequencing and whole-genome sequencing (WGS) using Oxford Nanopore Technology platform were used for genomic characterization. Results: Reverse transcriptase RT-PCR and qRT-PCR analysis detected chikungunya virus (CHIKV) in mosquito samples. Six CHIKV isolates were obtained. WGS revealed four nonsynonymous mutations in the structural polyprotein region, and five in the nonstructural polyprotein encoding region when compared with Yawat-2000 and Shivane-2016 strains. Sixty-four nucleotide changes in the nonstructural polyprotein region and 35 in the structural polyprotein region were detected. One isolate had an exclusive amino acid change, T1123I, in the nsP2 (protease) region. Conclusion: Abundant Ae. aegypti breeding and detection of CHIKV RNA in mosquitoes confirmed it as a chikungunya outbreak. Novel mutations detected in the epidemic strain warrants investigations to address their role in disease severity, transmission, and fitness.

Vector competence of three species of mosquitoes to Ingwavuma virus (Manzanilla orthobunyavirus), a new bunyavirus found circulating in India.

Ingwavuma virus (INGV), a mosquito-borne arbovirus reported from Africa and Southeast Asia has been found circulating in India as evidenced by virus isolation and antibody prevalence. INGV is now classified as Manzanilla orthobunyavirus belonging to family Peribunyaviridae. The virus is maintained in nature in a pig-mosquito-bird cycle. Human infection has been confirmed by virus isolation and detection of neutralizing antibodies. A study was initiated to determine the vector competence of Aedes aegypti, Culex quinquefasciatus, and Cx tritaeniorhynchus mosquitoes to INGV due to their high prevalence in India. Mosquitoes were oral fed on viraemic mice and INGV dissemination to legs, wings, salivary glands (saliva) was studied alongwith virus growth kinetics. The three mosquitoes replicated INGV with maximum titers of 3.7, 3.7 and 4.7log10TCID50/ml respectively and maintained the virus till 16th day post infection. However, vector competence and horizontal transmission to infant mouse was demonstrated only by Cx quinquefasciatus mosquitoes. Vertical or trans-ovarial transmission of INGV could not be demonstrated in the mosquito during the study. Though no major outbreak involving humans has been reported yet, the potential of the virus to replicate in different species of mosquitoes and vertebrates including humans pose a threat to public health should there be a change in its genome.

Oxylipin-PPARγ-initiated adipocyte senescence propagates secondary senescence in the bone marrow.

The chronic use of glucocorticoids decreases bone mass and quality and increases bone-marrow adiposity, but the underlying mechanisms remain unclear. Here, we show that bone-marrow adipocyte (BMAd) lineage cells in adult mice undergo rapid cellular senescence upon glucocorticoid treatment. The senescent BMAds acquire a senescence-associated secretory phenotype, which spreads senescence in bone and bone marrow. Mechanistically, glucocorticoids increase the synthesis of oxylipins, such as 15d-PGJ2, for peroxisome proliferator-activated receptor gamma (PPARγ) activation. PPARγ stimulates the expression of key senescence genes and also promotes oxylipin synthesis in BMAds, forming a positive feedback loop. Transplanting senescent BMAds into the bone marrow of healthy mice is sufficient to induce the secondary spread of senescent cells and bone-loss phenotypes, whereas transplanting BMAds harboring a p16INK4a deletion did not show such effects. Thus, glucocorticoid treatment induces a lipid metabolic circuit that robustly triggers the senescence of BMAd lineage cells that, in turn, act as the mediators of glucocorticoid-induced bone deterioration.

Basal and immune-responsive transcript expression of two Atlantic salmon interferon regulatory factor 2 (irf2) paralogues.

Atlantic salmon (Salmo salar) is one of the most economically important aquaculture species globally. However, disease has become a prevalent threat to this industry. A thorough understanding of the genes and molecular pathways involved in the immune responses of Atlantic salmon is imperative for selective breeding of disease-resistant broodstock, as well as developing new diets and vaccines to mitigate the impact of disease. Members of the interferon regulatory factor (IRF) family of transcription factors play roles in the induction of interferons and other cytokines involved in host immune responses to intracellular and parasitic pathogens. IRF family members also play diverse roles in other biological processes, such as stress response, reproduction and development. The current study focused on one member of the IRF family: interferon regulatory factor 2 (irf2). As previously shown, due to the genome duplication that occurred ∼80 million years ago in the salmonid lineage, there are two irf2 paralogues in the Atlantic salmon genome. In silico analyses at the cDNA and deduced amino acid levels were conducted followed by phylogenetic tree construction with IRF2 amino acid sequences from various ray-finned fishes, cartilaginous fish and tetrapods. qPCR was then used to analyze paralogue-specific irf2 constitutive expression across 17 adult tissues, as well as responses to the viral mimic pIC (i.e., synthetic double-stranded RNA analog) in cultured macrophage-like cells (in vitro) and to infection with the Gram-negative bacterium Moritella viscosa in skin samples (in vivo). The qPCR studies showed sex- and paralogue-specific differences in expression across tissues. For example, expression of both paralogues was higher in ovary than in testes; expression (considering both sexes together) was highest for irf2-1 in gonad and for irf2-2 in hindgut. Both irf2 paralogues were responsive to pIC stimulation, but varied in their induction level, with irf2-1 having an overall stronger response than irf2-2. Only one paralogue, irf2-2, was significantly responsive to M. viscosa infection. Differences in irf2-1 and irf2-2 transcript expression levels constitutively across tissues, and in response to pIC and M. viscosa, may suggest neo- or subfunctionalization of the duplicated genes. This novel information expands current knowledge and provides insight into how genome duplication events may impact host regulation of important immune markers.

Challenges in Accessing and Delivering Maternal and Child Health Services during the COVID-19 Pandemic: A Cross-Sectional Rapid Survey from Six States of India.

BACKGROUND/OBJECTIVES: Globally, the COVID-19 pandemic and its prevention and control policies have impacted maternal and child health (MCH) services. This study documents the challenges faced by patients in accessing MCH services, and the experiences of health care providers in delivering those services during the COVID-19 outbreak, explicitly focusing on the lockdown period in India. METHODS: A cross-sectional study (rapid survey) was conducted in 18 districts from 6 states of India during March to June, 2020. The sample size included 540 MCH patients, 18 gynaecologists, 18 paediatricians, 18 district immunisation officers and 108 frontline health workers. Bivariate analysis and multivariable analysis were used to assess the association between sociodemographic characteristics, and challenges faced by the patients. RESULTS: More than one-third of patients (n = 212; 39%) reported that accessing MCH services was a challenge during the lockdown period, with major challenges being transportation-related difficulties (n = 99; 46%) unavailability of hospital-based services (n = 54; 23%) and interrupted outreach health services (n = 39; 18.4%). The supply-side challenges mainly included lack of infrastructural preparedness for outbreak situations, and a shortage of human resources. CONCLUSIONS/RECOMMENDATIONS: A holistic approach is required that focuses on both preparedness and response to the outbreak, as well reassignment and reinforcement of health care professionals to continue catering to and maintaining essential MCH services during the pandemic.

Sociodemographic determinants of high tobacco use in Gond tribe of central India.

Background The prevalence of tobacco use is high in rural India, but limited information on tobacco use among the tribal population is available. We assessed the prevalence of tobacco use and type of tobacco use in the Gond tribal population. Methods We did a cross-sectional survey among the Gond tribal population residing in the Kundam block of Jabalpur district in Madhya Pradesh state in India. The study was carried out among persons aged 6 years and above during February-May 2017. Pre-tested interview schedules were used by trained field investigators to collect information on tobacco use. Results A total of 3351 individuals were included in this study, of which 58% were using some form of tobacco. The prevalence of tobacco use was higher among men compared to women, and it increased significantly from age 6 to 25 in both men and women. Tobacco use was significantly associated with age, gender and educational status of the respondents. Conclusion The study highlights a high tobacco use in the Gond tribe population. The high prevalence of tobacco use in younger ages is a matter of serious concern. The study establishes a need for information, education and communication and behavioural change communication activities; health camps focusing on the harmful effects of tobacco use and tobacco control campaign among tribal communities, tribal schools and ashrams.

A study of rhino-orbito-cerebral mucormycosis with COVID-19: A new challenge in North West of Rajasthan.

Background: Mucormycosis is a life-threatening fungal disease in immunocompromised patients. There has been increase in the number of mucormycosis associated with COVID-19 patients in second wave. Now country battle with both COVID-19 and mucormycosis. An invasive mucormycosis infection has been a significant burden in India after COVID-19. It has been recently emerged a notifiable disease by the Rajasthan government. Our aim is to develop awareness regarding the importance of early detection and treatment of mucormycosis with COVID-19 and reduce the morbidity and mortality. Materials and Methods: This is a Prospective longitudinal study including 34 patients diagnosed with acute invasive fungal infection by contrast enhancement magnetic resonance imaging studies of paranasal, orbit and brain or nasal biopsy for KOH/culture. Diagnosis is made through routine blood tests, biopsy, and radiological imaging. The patients taken for the study were COVID-19 reverse transcription-polymerase chain reaction positive or recent post COVID-19 (within 15 days) or symptoms of COVID-19 with bilateral pneumonitis. The study was conducted with 34 patients admitted to the department of medicine with mucormycosis within a month may 2021. Results: A total of 34 patients with a mean age of 50.92 years old and male female ratio 24/10 (70.5/29.41) were included in this study. The most common comorbidity was diabetes mellitus (23 patients 67.64%). Nine patients were newly diagnosed or recent onset of diabetes with or after COVID-19 infection. Twenty-four (70.58%) patients were COVID-19 positive or recent (within 15 days) history of COVID-19 positive. Seven (20.58) patients had the history of steroid as a treatment during COVID-19 and 5 (14.70) patients was on oxygen inhalation. One (2.94%) patient was fully vaccinated, and 5 (14.70) patients had the history of steam inhalation. The most common involvement was naso-orbital mucormycosis found in 28 patients (82.35%) followed by nasal-and orbital 26 (76.47) and 18 (52.94), respectively. Naso-Orbito-Cerebral was seen in 16 (47.05) patients. The more common reported symptoms and signs were headache (76.47), facial numbness (64.70), Nasal discharge (52.94), and ophthalmoplegia (52.94). Cranial nerve involvement was seen in 10 patients (facial palsy in 8 patients and bulbar palsy in 2 patients). Total mortality was 7 (7/34 20.58%). Conclusion: COVID-19 infection associated with the wide range of invasive mucormycosis. Early diagnosis and Clinical suspicion of acute invasive fungal sinusitis among COVID-19 patients is essential for better outcomes and higher survival.

Résumé Contexte: La mucormycose est une maladie fongique mortelle chez les patients immunodéprimés. Il y a eu une augmentation du nombre de mucormycose associée aux patients Covid - 19 en deuxième vague. Maintenant, le pays se bat contre le Covid-19 et la mucormycose. Une infection invasive en mucormycose a été une charge significative en Inde après Covid - 19. Il a récemment émergé une maladie notifiable du gouvernement du Rajasthan. Notre objectif est de sensibiliser à l'importance de la détection et du traitement précoce de la mucormycose avec Covid-19 et de réduire la morbidité et la mortalité. Matériaux et méthodes: Il s'agit d'une étude longitudinale prospective comprenant 34 patients diagnostiqués avec une infection fongique invasive aiguë par un contraste d'imagerie magnétique des études d'imagerie par résonance magnétique de biopsie paranasale, en orbite et au cerveau ou nasale pour le KOH / la culture. Le diagnostic est posé par des tests sanguins de routine, une biopsie et une imagerie radiologique. Les patients pris pour l'étude ont été la réaction en chaîne de la transcription inverse de Covid-19, la réaction en chaîne de polymérase positive ou le post-COVID-19 récent (dans les 15 jours) ou les symptômes de Covid-19 avec une pneumonite bilatérale. L'étude a été menée avec 34 patients admis au Département de médecine avec mucormycose dans un mois en mai 2021. Résultats: Un total de 34 patients avec un âge moyen de 50,92 ans et un rapport féminine masculin 24/10 (70,5 / 29,41) ont été inclus dans cette étude. La comorbidité la plus courante était le diabète sucré (23 patients 67,64%). Neuf patients ont été récemment diagnostiqués ou un début récent du diabète avec ou après l'infection à Covid - 19. Vingt-quatre (70,58%) patients étaient des antécédents de Covid - 19 positifs ou récents (dans les 15 jours) de Covid - 19 positifs. Sept (20,58) patients avaient des antécédents de stéroïde comme traitement pendant les patients COVID-19 et 5 (14,70) étaient sous inhalation d'oxygène. Un patient (2,94%) a été entièrement vacciné et 5 (14,70) patients avaient des antécédents d'inhalation de vapeur. L'atteinte la plus courante était la mucormycose naso-orbitale trouvée chez 28 patients (82,35%), suivie respectivement par l'orbital nasal et orbital 26 (76,47) et 18 (52,94). Le naso - orbito-cervebral a été observé chez 16 (47,05) patients. Les symptômes et les signes rapportés les plus courants étaient des maux de tête (76,47), un engourdissement facial (64,70), une décharge nasale (52,94) et une ophtalmoplégie (52,94). Une atteinte du nerf crânien a été observée chez 10 patients (paralysie faciale chez 8 patients et paralysie bulbaire chez 2 patients). La mortalité totale était de 7 (7/34 20,58%). Conclusion: Infection Covid - 19 associée à la large gamme de mucormycose invasive. Le diagnostic précoce et la suspicion clinique de sinusite fongique invasive aiguë chez les patients COVID-19 sont essentiels pour de meilleurs résultats et une survie plus élevée. Mots-clés: Covid - 19, fongique, invasive, nasal, rhinocéros orbital cerebral.

Multi-Organ Transcriptome Response of Lumpfish (Cyclopterus lumpus) to Aeromonas salmonicida Subspecies salmonicida Systemic Infection.

Lumpfish is utilized as a cleaner fish to biocontrol sealice infestations in Atlantic salmon farms. Aeromonas salmonicida, a Gram-negative facultative intracellular pathogen, is the causative agent of furunculosis in several fish species, including lumpfish. In this study, lumpfish were intraperitoneally injected with different doses of A. salmonicida to calculate the LD50. Samples of blood, head-kidney, spleen, and liver were collected at different time points to determine the infection kinetics. We determined that A. salmonicida LD50 is 102 CFU per dose. We found that the lumpfish head-kidney is the primary target organ of A. salmonicida. Triplicate biological samples were collected from head-kidney, spleen, and liver pre-infection and at 3- and 10-days post-infection for RNA-sequencing. The reference genome-guided transcriptome assembly resulted in 6246 differentially expressed genes. The de novo assembly resulted in 403,204 transcripts, which added 1307 novel genes not identified by the reference genome-guided transcriptome. Differential gene expression and gene ontology enrichment analyses suggested that A. salmonicida induces lethal infection in lumpfish by uncontrolled and detrimental blood coagulation, complement activation, inflammation, DNA damage, suppression of the adaptive immune system, and prevention of cytoskeleton formation.

Prediction of chemical warfare agents based on cholinergic array type meta-predictors.

Molecular insights into chemical safety are very important for sustainable development as well as risk assessment. This study considers how to manage future upcoming harmful agents, especially potentially cholinergic chemical warfare agents (CWAs). For this purpose, the structures of known cholinergic agents were encoded by molecular descriptors. And then each drug target interaction (DTI) was learned from the encoded structures and their cholinergic activities to build DTI classification models for five cholinergic targets with reliable statistical validation (ensemble-AUC: up to 0.790, MCC: up to 0.991, accuracy: up to 0.995). The collected classifiers were transformed into 2D or 3D array type meta-predictors for multi-task: (1) cholinergic prediction and (2) CWA detection. The detection ability of the array classifiers was verified under the imbalanced dataset between CWAs and none CWAs (area under the precision-recall curve: up to 0.997, MCC: up to 0.638, F1-score of none CWAs: up to 0.991, F1-score of CWAs: up to 0.585).

Subtype and cell type specific expression of lncRNAs provide insight into breast cancer.

Long non-coding RNAs (lncRNAs) are involved in breast cancer pathogenesis through chromatin remodeling, transcriptional and post-transcriptional gene regulation. We report robust associations between lncRNA expression and breast cancer clinicopathological features in two population-based cohorts: SCAN-B and TCGA. Using co-expression analysis of lncRNAs with protein coding genes, we discovered three distinct clusters of lncRNAs. In silico cell type deconvolution coupled with single-cell RNA-seq analyses revealed that these three clusters were driven by cell type specific expression of lncRNAs. In one cluster lncRNAs were expressed by cancer cells and were mostly associated with the estrogen signaling pathways. In the two other clusters, lncRNAs were expressed either by immune cells or fibroblasts of the tumor microenvironment. To further investigate the cis-regulatory regions driving lncRNA expression in breast cancer, we identified subtype-specific transcription factor (TF) occupancy at lncRNA promoters. We also integrated lncRNA expression with DNA methylation data to identify long-range regulatory regions for lncRNA which were validated using ChiA-Pet-Pol2 loops. lncRNAs play an important role in shaping the gene regulatory landscape in breast cancer. We provide a detailed subtype and cell type-specific expression of lncRNA, which improves the understanding of underlying transcriptional regulation in breast cancer.