High Fatality Rate Research Articles

Predicting Coronary Artery Disease Using Machine Learning

Developing a predictive model for detecting Coronary Artery Disease (CAD) is crucial due to its high global fatality rate of approximately 17.9 million people annually. With the advancements in artificial intelligence, the availability of large-scale data, and increased access to computational capability, it is feasible to create robust models that can detect CAD with high precision. This study aims to build a predictive model that can assist health workers in the timely detection of CAD and ultimately reduce mortality. This study performs a comparative analysis of four supervised classification machine learning algorithms- Logistic regression (LR), Support vector machine (SVM), Extreme gradient boosting (XGBoost), and Artificial neural network (ANN),  in predicting the case-control status of the patient. Chi-squared and lasso criteria are employed to select the most relevant ones from the available features. The performance of the employed models is compared using sensitivity, specificity, accuracy, and the area under the receiver operating characteristic (ROC) curve (AUC). The experimental results indicate that the LR model is the most effective and accurate among the models tested, and its implementation can improve the detection of CAD in clinical settings.

Antibiotic resistance trends among Vibrio vulnificus and Vibrio parahaemolyticus isolated from the Chesapeake Bay, Maryland: a longitudinal study.

Antibiotics are often used to treat severe Vibrio infections, with third-generation cephalosporins and tetracyclines combined or fluoroquinolones alone being recommended by the US Centers for Disease Control and Prevention. Increases in antibiotic resistance of both environmental and clinical vibrios are of concern; however, limited longitudinal data have been generated among environmental isolates to inform how resistance patterns may be changing over time. Hence, we evaluated long-term trends in antibiotic resistance of vibrios isolated from Chesapeake Bay waters (Maryland) across two 3-year sampling periods (2009-2012 and 2019-2022). Vibrio parahaemolyticus (n = 134) and Vibrio vulnificus (n = 94) toxR-confirmed isolates were randomly selected from both sampling periods and tested for antimicrobial susceptibility against eight antibiotics using the Kirby-Bauer disk diffusion method. A high percentage (94%-96%) of V. parahaemolyticus isolates from both sampling periods were resistant to ampicillin and only 2%-6% of these isolates expressed intermediate resistance or resistance to third-generation cephalosporins, amikacin, tetracycline, and trimethoprim-sulfamethoxazole. Even lower percentages of resistant V. vulnificus isolates were observed and those were mostly recovered from 2009 to 2012, however, the presence of multiple virulence factors was observed. The frequency of multi-drug resistance was relatively low (6%-8%) but included resistance against antibiotics used to treat severe vibriosis in adults and children. All isolates were susceptible to ciprofloxacin, a fluoroquinolone, indicating its sustained efficacy as a first-line agent in the treatment of severe vibriosis. Overall, our data indicate that antibiotic resistance patterns among V. parahaemolyticus and V. vulnificus recovered from the lower Chesapeake Bay have remained relatively stable since 2009.IMPORTANCEVibrio spp. have historically been susceptible to most clinically relevant antibiotics; however, resistance and intermediate-resistance have been increasingly recorded in both environmental and clinical isolates. Our data showed that while the percentage of multi-drug resistance and resistance to antibiotics was relatively low and stable across time, some Vibrio isolates displayed resistance and intermediate resistance to antibiotics typically used to treat severe vibriosis (e.g., third-generation cephalosporins, tetracyclines, sulfamethoxazole-trimethoprim, and aminoglycosides). Also, given the high case fatality rates observed with Vibrio vulnificus infections, the presence of multiple virulence factors in the tested isolates is concerning. Nevertheless, the continued susceptibility of all tested isolates against ciprofloxacin, a fluoroquinolone, is indicative of its use as an effective first-line treatment of severe Vibrio spp. infections stemming from exposure to Chesapeake Bay waters or contaminated seafood ingestion.

Naegleria fowleri 98 Percent Fatal a Comprehensive Survey

Naegleria fowleri, colloquially termed the "brain-eating amoeba," presents a formidable public health concern due to its astonishingly high fatality rate of 98%. This abstract provides a thorough examination of the various aspects surrounding Naegleria fowleri, encompassing its morphology, life cycle, transmission routes, clinical manifestations, diagnostic methods, treatment strategies, and preventive measures. Naegleria fowleri, an amoeboid protist, thrives in warm freshwater environments, predominantly in regions with elevated temperatures. Infections occur when contaminated water enters the nasal passages, leading to primary amebic meningoencephalitis (PAM), an acute and often fatal condition affecting the central nervous system. The clinical course of PAM is rapid, with symptoms escalating from initial flu-like manifestations to severe neurological impairment within days. Diagnosis of PAM remains challenging, relying on specialized laboratory techniques such as polymerase chain reaction (PCR) and immunofluorescence assays. Despite efforts to develop effective treatments, mortality rates remain alarmingly high, emphasizing the critical importance of preventive measures. Avoiding freshwater activities in warm, stagnant water bodies, utilizing nose clips or plugs during water-related activities, and ensuring proper disinfection of recreational water sources are key strategies in mitigating the risk of the risk of Naegleria fowleri infections and reducing its devastating impact on public health.

Therapeutic options for different metastatic sites arising from renal cell carcinoma: A review.

Renal cell carcinoma (RCC) stands among the top 10 malignant neoplasms with the highest fatality rates. It exhibits pronounced heterogeneity and robust metastatic behavior. Patients with RCC may present with solitary or multiple metastatic lesions at various anatomical sites, and their prognoses are contingent upon the site of metastasis. When deliberating the optimal therapeutic approach for a patient, thorough evaluation of significant risk factors such as the feasibility of complete resection, the presence of oligometastases, and the patient's functional and physical condition is imperative. Recognizing the nuanced differences in RCC metastasis to distinct organs proves advantageous in contemplating potential treatment modalities aimed at optimizing survival outcomes. Moreover, discerning the metastatic site holds promise for enhancing risk stratification in individuals with metastatic RCC. This review summarizes the recent data pertaining to the current status of different RCC metastatic sites and elucidates their role in informing clinical management strategies across diverse metastatic locales of RCC.

Molecular insights into the Ebola virus life cycle.

Ebola virus and other orthoebolaviruses cause severe haemorrhagic fevers in humans, with very high case fatality rates. Their non-segmented single-stranded RNA genome encodes only seven structural proteins and a small number of non-structural proteins to facilitate the virus life cycle. The basics of this life cycle are well established, but recent advances have substantially increased our understanding of its molecular details, including the viral and host factors involved. Here we provide a comprehensive overview of our current knowledge of the molecular details of the orthoebolavirus life cycle, with a special focus on proviral host factors. We discuss the multistep entry process, viral RNA synthesis in specialized phase-separated intracellular compartments called inclusion bodies, the expression of viral proteins and ultimately the assembly of new virus particles and their release at the cell surface. In doing so, we integrate recent studies into the increasingly detailed model that has developed for these fundamental aspects of orthoebolavirus biology.

Unveiling the role of APOM gene in liver cancer: Investigating the impact of hsa-miR-4489/MUC1-mediated ferroptosis on the advancement of hepatocellular carcinoma cells

Primary liver cancer has consistently exhibited a high prevalence and fatality rate, necessitating the investigation of associated diagnostic markers and inhibition mechanisms to effectively mitigate its impact. The significance of apolipoprotein M (ApoM) in impeding the progression of neoplastic ailments is progressively gaining recognition. However, a comprehensive understanding of its underlying mechanism in liver cancer advancement remains to be elucidated. Recent evidence indicates a potential association between ApoM and polyunsaturated fatty acids (PUFAs), with the peroxidation of phospholipids (PLs) containing PUFAs being recognized as a crucial element in the occurrence of ferroptosis. This prompts us to investigate the impact of the APOM gene on the progression of liver cancer through the ferroptosis pathway and elucidate its underlying mechanisms. The findings of this study indicate that the liver cancer cell model, which was genetically modified to overexpress the APOM gene, demonstrated a heightened ferroptosis effect. Moreover, the observed inhibition of the GSH (Glutathione) − GPX4 (Glutathione Peroxidase 4) regulatory axis suggests that the role of this axis in inhibiting ferroptosis is weakened. Through intersection screening and validation, we found that Mucin 1,cell surface associated (MUC1) can inhibit ferroptosis and is regulated by the APOM gene. Bioinformatics analysis and screening identified miR-4489 as a mediator between the two. Experimental results using the dual luciferase reporter gene confirmed that has-miR-4489 targets MUC1′s 3′-UTR and inhibits its expression. In conclusion, this study provides evidence that the APOM gene induces a down-regulation in the expression of the ferroptosis-inhibiting gene MUC1, mediated by miR-4489, thereby impeding the advancement of liver cancer cells through the facilitation of ferroptosis.

Predictors of Fatal Outcome in Newly Diagnosed Tuberculosis/HIV Co-Infection with Chronic Alcoholism (Clinical Case)

Our own case of tuberculosis/HIV co-infection’s diagnosis in chronic alcoholism and analysis of the fatal outcome predictors are presented. The patient abused alcohol for a long time in the presented case, he was hospitalised with acute psychosis in a psychoneurological dispensary, where pulmonary tuberculosis and HIV infection were diagnosed for the first time during additional examination. The patient was admitted to the department in serious condition after prolonged alcohol intoxication. The patient’s condition stabilized after detoxification therapy. Antimycobacterial therapy according to the scheme of an individual treatment regimen, antiretroviral therapy, treatment of hepatitis B and C, detoxification therapy, prophylaxis with Biseptol and Fluconazole and symptomatic therapy were prescribed. After 20 days immune reconstitution inflammatory syndrome developed. It was manifested with meningitis and cryptococci were detected in the cerebrospinal fluid 17 days later. Prescribed treatment of cryptococcal meningoencephalitis with fluconazole in high doses intravenously had a significant positive effect, which made it possible to reduce the dose of the drug to the maintenance level. The treatment was not stopped, but sterility of the liquor was not achieved. After 98 days the patient entered a coma and after 113 days he died from the progression of multiple organ failure and cryptococcal meningitis. It should be noted that the patient was diagnosed with tuberculosis with multiple drug resistance for the first time, the treatment of which had positive dynamics, despite the progression of multiple organ failure and the presence of cryptococcal meningoencephalitis. Therefore, although tuberculosis was not the direct cause of the patient’s death, the disease itself deepened the severity of the general condition. Considering the presented clinical case, it was established that predictors of the fatal outcome of newly diagnosed tuberculosis/HIV co-infection in chronic alcoholism are: antisocial lifestyle; concomitant diseases (tuberculosis, chronic viral hepatitis B and C); cryptococcal meningoencephalitis; fever, altered mental status, cryptococci in the cerebrospinal fluid; the number of CD4+ lymphocytes is less than 200/μL; lack of early screening for CrAg; early initiation of antiretroviral therapy before the diagnosis of cryptococcal meningoencephalitis, which provokes immune reconstitution inflammatory syndrome, against the background of which cryptococcal infection progresses; monotherapy of cryptococcal meningoencephalitis with Fluconazole. Knowledge and practice gaps among medical practitioners contribute to the high fatality rate of cryptococcal meningoencephalitis in tuberculosis/HIV co-infection in chronic alcoholism.

Oxygen vacancy-rich nickel oxide nanoplatforms for enhanced photothermal and chemodynamic therapy combat methicillin-resistant Staphylococcus aureus

Bacterial infections pose a global concern due to high fatality rates, particularly with the rise of drug-resistant bacteria and biofilm formation. There is an urgent need for innovative strategies to combat this issue. A study on chemodynamic therapy (CDT) using nanozymes in conjunction with photothermal therapy (PTT) has displayed potential in addressing drug-resistant bacterial infections. However, the effectiveness of this combined approach is limited by inadequate light absorption. This work suggests the NiOx nanoparticles enriched with oxygen vacancies enhance CDT and PTT to overcome this challenge. The presence of oxygen vacancies in NiOx can reduce the energy gap between its valence band and conduction band, facilitating oxygen adsorption. NiOx has exhibited notable antibacterial properties and complete eradication of biofilms in both laboratory and animal trials. In animal abscess models, NiOx demonstrated antibacterial and anti-inflammatory effects in the initial stages, while also promoting wound healing and tissue regeneration by influencing immune factors and encouraging collagen deposition and neovascularization. With positive biosafety and biocompatibility profiles, the oxygen vacancy-enhanced CDT and PTT therapy proposed in this article hold promise for effective sterilization, deep biofilm removal, and treatment of infections caused by drug-resistant bacteria. Statement of significanceThis study constructs oxygen vacancies NiOx nanoparticles (NiOx NPs) to improve the efficacy of photothermal therapy and chemodynamic therapy. The presence of oxygen vacancies in NiOx NPs helps bridge the energy gap between its valence band and conduction band, facilitating oxygen adsorption and improving catalytic efficiency. In both in vivo and in vitro antibacterial experiments, NiOx NPs demonstrate effective antibacterial and anti-inflammatory properties. Furthermore, it aids in wound healing and tissue regeneration by modulating immune factors, collagen deposition, and angiogenesis. This approach presents a promising collaborative strategy for utilizing nickel-based defective nanomaterials in combating deep drug-resistant bacterial infections.

Effect of tocilizumab plus corticosteroid on clinical outcome in patients hospitalized with severe fever with thrombocytopenia syndrome: A randomized clinical trial

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P=0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P=0.002) compared to those receiving corticosteroids alone. A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.

SMYD2 induced PGC1α methylation promotes stemness maintenance of glioblastoma stem cells.

The high fatality rate of glioblastoma (GBM) is attributed to glioblastoma stem cells (GSCs), which exhibit heterogeneity and therapeutic resistance. Metabolic plasticity of mitochondria is the hallmark of GSCs. Targeting mitochondrial biogenesis of GSCs is crucial for improving clinical prognosis in GBM patients. SMYD2-induced PGC1α methylation and followed nuclear export are confirmed by co-immunoprecipitation, cellular fractionation, and immunofluorescence. The effects of SMYD2/PGC1α/CRM1 axis on GSCs mitochondrial biogenesis are validated by oxygen consumption rate, ECAR, and intracranial glioma model. PGC1α methylation causes the disabled mitochondrial function to maintain the stemness, thereby enhancing the radio-resistance of GSCs. SMYD2 drives PGC1α K224 methylation (K224me), which is essential for promoting the stem-like characteristics of GSCs. PGC1α K224me is preferred binding with CRM1, accelerating PGC1α nuclear export and subsequent dysfunction. Targeting PGC1α methylation exhibits significant radiotherapeutic efficacy and prolongs patient survival. These findings unveil a novel regulatory pathway involving mitochondria that govern stemness in GSCs, thereby emphasizing promising therapeutic strategies targeting PGC1α and mitochondria for the treatment of GBM.

Exploring odontogenic brain abscesses: a comprehensive review.

Whether in neurology or dentistry, odontogenic brain abscess stands as an ailment demanding undivided attention. The onset of this disease is insidious, with a relatively low incidence rate but a markedly high fatality rate. Moreover, its symptoms lack specificity, easily leading to misdiagnosis, oversight, and treatment delays. Hence, clinicians should maintain heightened vigilance when faced with pathogenic bacteria of dental origin in patients. This paper encapsulates the latest research findings on the clinical manifestations and essential treatment points of odontogenic brain abscess. It may offer a crucial reference for prompt diagnosis and improved therapeutic approaches. Odontogenic brain abscess, an infection of the cerebral parenchyma, usually appears in immunocompromised patients with dental ailments or postdental surgeries. The main pathogenic microorganisms include Streptococcus intermedius, Fusobacterium nucleatum, Streptococcus anginosus, and Millerella. Given the undetectable and nonspecific symptoms in patients, the diagnostic process relies on microbiological methods. Therefore, clinicians should actively investigate and identify the pathogenic microorganisms of odontogenic brain abscess for early detection and selection of appropriate treatment regimens to avoid disease management delays.

Frequency and outcome of sodium disturbances in children admitted with acute watery diarrhea in a tertiary hospital of Bangladesh

Background: Acute watery diarrhea (AWD) is one of the common causes of hospital admissions in pediatric age group. Majority of children with dehydration suffer from different electrolyte abnormalities which needs to be identified and treated. Objectives: To investigate the frequency and outcome of sodium disturbances in AWD among children admitted in a tertiary hospital in Bangladesh. Method: In this prospective observational study, 121 children of 2 months to 5 years of age admitted in the Department of Pediatrics, Chittagong Medical College Hospital with AWD were included. Clinical features and sodium levels on admission were recorded. Patients were followed up during their hospital stay to record the outcomes. Children were grouped in hyponatremia (serum sodium <135mmol/l), hypernatremia (serum sodium >145mmol/l) and normonatremia (serum sodium 135–145mmol/l) and compared. Results: Of the 121 children, 38.0% and 62.0% had moderate and severe dehydration, respectively. The majority (58.7%) had normal sodium levels. Sodium disturbances was found in 41.3% cases. There were 26.4% cases of hypernatremia and 14.9% cases of hyponatremia among them. Out of 18 hyponatremic patients, 77.8% had mild hyponatremia and the rest 22.2% had moderate hyponatremia. Among 32 hypernatremic children, 62.4% had mild, 18.8% had moderate and 18.8% had severe hypernatremia. The case fatality rate was 2.6% and all of them had hypernatremic dehydration at admission. Conclusion: Sodium disturbances particularly hypernatremia is more frequent and is associated with high case fatality rate among children hospitalized with acute watery diarrhoea. BANGLADESH J CHILD HEALTH 2022; VOL 46 (3) : 110-114

SFTSV nucleoprotein mediates DNA sensor cGAS degradation to suppress cGAS-dependent antiviral responses.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.

Rhamnopyranoside Pivaloyl Esters as Black and White Fungus Inhibitors: Molecular Docking, Dynamics and ADMET Analysis

The "Black and White Fungus" is a very infrequently developing pathogen with a high fatality rate that has prompted widespread public health concern during the period of the COVID-19 pandemic. This pathogenic fungus may be widely distributed in nature, in plants, and in deteriorating fruits and vegetables because of its widespread nature. Numerous sugar molecules, such as glucopyranoside and glucofuranose, have been reported to have significant antibacterial, antifungal, and antiviral activity, and they were also revealed to be able to inhibit multidrug-resistant microorganisms. The recent black fungus epidemic was extremely serious in India, combined with COVID-19, which contributed to the high mortality impact and deterioration of the situation due to the unavailability of effective treatments. So, rhamnopyranose type derivatives 1–9 were studied against the proteins associated with black and white fungi such as Mycolicibacterium smegmatis (PDB ID 7D6X), Rhizomucor miehei (PDB ID 4WTP), Candida auris (PDB ID 6U8J), and Aspergillus luchuensis (PDB 1BK1). These compounds exhibited favorable physical and biochemical scores, as well as appropriate ADMET metrics, among other characteristics. Following the molecular docking procedure, it was found that 1–9 had the highest binding affinity in most cases, (> -6.00 kcal/mol), while compound 9 had outstanding binding affinity against Rhizomucor miehei (-8.7 kcal/mol) and against Mycolicibacterium smegmatis (-8.2 kcal/mol). In addition, the binding affinity against white fungus is also outstanding. This time, compounds 8 and 9 had better binding energy, which is -7.8 kcal/mol against Aspergillus luchuensis (1BK1) and -7.6 kcal/mol against Candida auris (6U8J). Finally, the molecular dynamics simulation at 100 ns has proved that they are stable for new medication development. Among the derivatives 1–9, ligands 8 and 9 exhibited potential medicinal characteristics when all of the data were considered.

A dual-targeting approach using a human bispecific antibody against the receptor-binding domain of the Middle East Respiratory Syndrome Coronavirus

The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has posed a significant global health concern due to its severe respiratory illness and high fatality rate. Currently, despite the potential for resurgence, there are no specific treatments for MERS-CoV, and only supportive care is available. Our study aimed to address this therapeutic gap by developing a potent neutralizing bispecific antibody (bsAb) against MERS-CoV. Initially, we isolated four human monoclonal antibodies (mAbs) that specifically target the MERS-CoV receptor-binding domain (RBD) using phage display technology and an established human antibody library. Among these four selected mAbs, our intensive in vitro functional analyses showed that the MERS-CoV RBD-specific mAb K111.3 exhibited the most potent neutralizing activity against MERS-CoV pseudoviral infection and the molecular interaction between MERS-CoV RBD and human dipeptidyl peptidase 4. Consequently, we engineered a novel bsAb, K207.C, by utilizing K111.3 as the IgG base and fusing it with the single-chain variable fragment of its non-competing pair, K111.1. This engineered bsAb showed significantly enhanced neutralization potential against MERS-CoV compared to its parental mAb. These findings suggest that K207.C may serve as a potential candidate for effective MERS-CoV neutralization, further highlighting the promise of the bsAb dual-targeting approach in MERS-CoV neutralization.

STUDY OF FLOOD VULNERABILITY IN HIMALAYAN REGION: A CASE OF UTTRAKHAND

India's Himalayan area is well known for its magnificent scenery and abundant wildlife. However, because of its complicated geology, delicate ecosystems, and unpredictable climate, it is also extremely vulnerable to catastrophic calamities. The causes, effects, and mitigation techniques of the common natural catastrophes that affect India's Himalayan region—such as earthquakes, landslides, floods, and glacial lake outburst floods (GLOFs)—are briefly summarised in this summary. Because of the collision of the Indian and Eurasian tectonic plates, earthquakes are one of the most dangerous natural disasters in the Himalayan region. Major seismic events, like the one that struck Nepal in 2015, demonstrate how vulnerable the region's heavily inhabited areas are to devastating destruction and high fatality rates. Effective disaster preparedness and resilient infrastructure are crucial for minimizing casualties and damage. Another common risk in the Himalayan region is landslides, which can be brought on by unstable slopes, strong rains, and seismic activity. The region's susceptibility is exacerbated by these occurrences, which represent a major threat to natural ecosystems, transportation networks, and towns, particularly during the monsoon season. In the Himalayan region, floods are a common occurrence that are exacerbated by glacial melt, heavy rainfall, and glacier lake outbursts. Flash floods, like the ones that occurred in Uttarakhand in 2013, highlight the terrible effects on infrastructure, communities, and the environment. Reducing flood risks and increasing resilience requires community-based adaptation strategies, early warning systems, and sustainable land use planning. A unique hazard in the Himalayan region, glacial lake outburst floods (GLOFs) are caused by the rapid melting of glaciers and the creation of unstable glacial lakes. The communities, infrastructure, and ecosystems downstream are seriously threatened by these catastrophes, which calls for careful observation and risk assessment techniques. One of the worst natural catastrophes to have hit the state in recent memory is the flash floods in Uttarakhand. Because to the state's distinctive geography, which is made up of small valleys and steep hills, heavy rainfall events have a greater effect, especially during the monsoon season. 2013's devastating flash floods, brought on by abnormally high rainfall, caused extensive environmental damage, infrastructure ruin, and a great deal of fatalities. The abrupt influx of water, rubble, and silt caused great destruction to isolated communities, tourist attractions, and places of worship, underscoring the precariousness of human habitation in the foothills of the Himalayas. The incident also brought attention to the relationship between unplanned development, environmental deterioration, and the likelihood of disasters, spurring calls for more land use planning, early warning systems, and sustainable development techniques future flash floods in Uttarakhand. In conclusion, the broad range of natural hazards that the Himalayan area of India faces calls for multifaceted methods to disaster risk reduction and management. In this dynamic and vulnerable setting, scientific research, community participation, and sustainable development practices are critical components of effective resilience-building efforts. Keywords: Hilly areas natural disaster, flash flood, Glacial lake outburst, flash flood in Uttarakhand

ML3CNet: Non-local means-assisted automatic framework for lung cancer subtypes classification using histopathological images

Background and objective:Lung cancer (LC) has a high fatality rate that continuously affects human lives all over the world. Early detection of LC prolongs human life and helps to prevent the disease. Histopathological inspection is a common method to diagnose LC. Visual inspection of histopathological diagnosis necessitates more inspection time, and the decision depends on the subjective perception of clinicians. Usually, machine learning techniques mostly depend on traditional feature extraction which is labor-intensive and may not be appropriate for enormous data. In this work, a convolutional neural network (CNN)-based architecture is proposed for the more effective classification of lung tissue subtypes using histopathological images. Methods:Authors have utilized the first-time nonlocal mean (NLM) filter to suppress the effect of noise from histopathological images. NLM filter efficiently eliminated noise while preserving the edges of images. Then, the obtained denoised images are given as input to the proposed multi-headed lung cancer classification convolutional neural network (ML3CNet). Furthermore, the model quantization technique is utilized to reduce the size of the proposed model for the storage of the data. Reduction in model size requires less memory and speeds up data processing. Results:The effectiveness of the proposed model is compared with the other existing state-of-the-art methods. The proposed ML3CNet achieved an average classification accuracy of 99.72%, sensitivity of 99.66%, precision of 99.64%, specificity of 99.84%, F-1 score of 0.9965, and area under the curve of 0.9978. The quantized accuracy of 98.92% is attained by the proposed model. To validate the applicability of the proposed ML3CNet, it has also been tested on the colon cancer dataset. Conclusion:The findings reveal that the proposed approach can be beneficial to automatically classify LC subtypes that might assist healthcare workers in making decisions more precisely. The proposed model can be implemented on the hardware using Raspberry Pi for practical realization.

The hidden burden of melioidosis in Nepal: a paradigm for the urgent need to implement a simple laboratory algorithm to detect Burkholderia pseudomallei in low-resource endemic areas

Melioidosis, an emerging infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is massively underdiagnosed in many low- and middle-income countries. The disease is clinically extremely variable, has a high case fatality rate, and is assumed to be highly endemic in South Asian countries, including Nepal. The reasons for underdiagnosis include the lack of awareness among clinicians and laboratory staff and limited microbiological capacities. Because costly laboratory equipment and consumables are likely to remain a significant challenge in many melioidosis-endemic countries in the near future, it will be necessary to make optimum use of available tools and promote their stringent implementation. Therefore, we suggest that health facilities in resource-poor countries, such as Nepal, introduce a simple and low-cost diagnostic laboratory algorithm for the identification of B. pseudomallei cultures. This screening algorithm should be applied specifically to samples from patients with fever of unknown origin and risk factors for melioidosis, such as diabetes. In addition, there could also be a role of low-cost, novel, promising serological point-of-care tests, which are currently under research and development.

Human macrophages infected with Egyptian Rousette bat-isolated Marburg virus display inter-individual susceptibility and antiviral responsiveness

Marburg virus (MARV) is a highly pathogenic filovirus and a causative agent of sporadic zoonotic viral hemorrhagic fever outbreaks with high case fatality rates. In humans, filoviruses like MARV and Zaire Ebola virus (EBOV) target, among others, innate immune cells like dendritic cells and macrophages (MΦs). Filovirus-infected dendritic cells display impaired maturation and antigen presentation, while MΦs become hyper-activated and secrete proinflammatory cytokines and chemokines. Our current understanding of human macrophage responses to MARV remains limited. Here, we used human monocyte-derived macrophages (moMΦs) to address how their phenotype, transcriptional profile, and protein expression change upon an in vitro infection with a bat isolate of MARV. Confirming its tropism for macrophages, we show that MARV induces notable shifts in their transcription distinct from responses induced by lipopolysaccharide (LPS), marked by upregulated gene expression of several chemokines, type I interferons, and IFN-stimulated genes. MARV infection also elicited pronounced inter-individually different transcriptional programs in moMΦs, the induction of Wnt signaling-associated genes, and the downregulation of multiple biological processes and molecular pathways.

FREQUENCY OF EARLY STENT THROMBOSIS (ACUTE AND SUBACUTE) IN PATIENTS PRESENTING WITH ACUTE ST ELEVATION MYOCARDIAL INFARCTION (STEMI) UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION (PCI)

Sudden cardiac stent thrombosis (ST) is a severe clinical risk that can lead to high fatality rates. However, data are scarce on the prevalence of early ST events following ‘primary percutaneous coronary intervention’ (pPCI) and the characteristics that predict it, particularly among Pakistani patients. Objective: The objective is to determine possible indicators and evaluate ‘the frequency of acute and sub-acute stent thrombosis’ (ST) after ‘primary percutaneous coronary intervention’ (PCI). Methods: Five hundred individuals who had undergone primary PCI were enrolled from July 2022 to December 2023. Telephone follow-up assessments were used to gather information on 30-day results, including death rates, recurrence of symptoms, and episodes of ST. ‘ST was classified as acute’ (occurring ‘during the procedure’) or ‘sub-acute’ (‘occurring within 30 days post-procedure) using standardised criteria established by the ‘Academic Research Consortium. Results: In this study, 500 patients were enrolled, primarily male (80.4%, 362 patients). ‘Stent thrombosis’ (either acute or sub-acute) was observed in 6.8% of patients, with 10.1% (4) classified as definite ST and the remaining 91.9% (34) as probable ST. Male patients were more prevalent among those who developed ST, along with a higher incidence of hypertension, diabetes, reduced left ventricular ejection fraction (LVEF) pre-PCI, and higher Killip Class. Patients with ST experienced a higher in-hospital mortality rate compared to those without ST, with a p-value of 0.02. Notably, ‘Killip Class’ (‘III-IV’) emerged as ‘an independent ST predictor in this patient cohort. These findings underscore the importance of risk assessment and vigilant management, particularly in patients presenting with higher Killip Class and other associated risk factors, to mitigate ST occurrence and adverse outcomes following primary PCI. Conclusion: Early stent thrombosis (ST) appears relatively common in patients undergoing primary PCI. Those with diabetes and hypertension face an elevated risk of ST, while patients presenting in ‘Killip Class III-IV’ demonstrate an ‘independent predictive’ factor for early ST.