High Fatality Rate Research Articles

Soluplus-TPGS Mixed Micelles as a Delivery System for Brigatinib: Characterization and In Vitro Evaluation.

Lung cancer is a major public health concern, with a high incidence and fatality rate. Its treatment is very difficult, as it is mostly diagnosed in advanced stages. Non-small cell lung carcinoma (NSCLC) is the major form of lung carcinoma that persists. Brigatinib (BGT), a powerful small-molecule tyrosine kinase inhibitor, has demonstrated significant therapeutic potential in the treatment of NSCLC with anaplastic lymphoma kinase (ALK) mutations. However, the therapeutic applicability of BGT is hampered by its low solubility and bioavailability. In this study, we developed a mixed micelle system comprising Soluplus and TPGS loaded with BGT. BGT was encapsulated into the mixed micelles using various combinations of Soluplus and TPGS, with encapsulation efficiency (EE%) ranging from 52.43 ± 1.07 to 97.88 ± 2.25%. The dynamic light scattering data showed that the mixed micelles ranged in size from 75.7 ± 0.46 to 204.3 ± 5.40 nm. The selected mixed micelles (F6) showed approximately 38% BGT release in the first 2 h, and subsequently, within 72 h, the release was 94.50 ± 5.90%. The NMR experiment confirmed the formation of micelles. Additionally, the mixed micelles showed significantly higher cellular uptake (p < 0.05) and increased cytotoxicity (p < 0.05) as compared to the free BGT. Specifically, the obtained IC50 values for BGT-loaded Soluplus-TPGS mixed micelles and free BGT were 22.59 ± 6.07 and 61.45 ± 6.35 μg/mL, respectively. The results of the in vitro stability experiment showed that the selected mixed micelle (F6) was stable at both room temperature and 4 °C, with only minor changes in size and PDI. Our results indicate great potential for the developed Soluplus-TPGS mixed micelles as a delivery system for BGT.

Treatment outcomes in retinoblastoma and the effect of tumor topography.

Retinoblastoma, the most common intraocular malignancy in children, has high fatality rates if untreated. It is crucial to monitor treatment effectiveness and explore factors influencing favorable outcomes. Our study aims to examine how tumor location impacts the response to standard treatments and the achievement of favorable outcomes among retinoblastoma patients, while controlling for other tumor-related factors. This retrospective study analyzed medical records of retinoblastoma patients from November 2012 to December 2022 enrolled in the retinoblastoma program at the Children's Cancer Center of Lebanon (established in collaboration with St.yJude Children's Research Hospital, Memphis, TN). Data were extracted from the electronic chart reviews and operative reports of examinations under anesthesia (EUAs), and included patient's demographics, tumor characteristics (size, location), and treatment parameters (treatment type, resolution, recurrence). The study included 42 patients with retinoblastoma, with a total of 57 eyes and 115 tumors/lesions. The median age at diagnosis was 12months (range: 2-36months). Among the patients, 26 (61.9%) were males and 16 (38.1%) were females. A minority of patients (21.4%) presented with unilateral involvement, whereas the majority (78.6%) had bilateral involvement. The locations of retinoblastoma lesions were distributed as follows: optic nerve (4.4%), macula (19.1%), superior (16.5%), inferior (17.4%), nasal (27.8%), and temporal (14.8%). Resolution rate tended to be highest for tumors close to optic nerve and temporal lesions, but no statistical significance was attained (p=.45). Macular lesions tended to have the fastest resolution, but again not significantly (p=.5). Multiple logistic regression revealed that the odds for resolution of tumor was not significantly associated with tumor size (p=.57) or location (p=.52). Location of retinoblastoma lesions was not directly associated with recurrence-free resolution in our cohort. Further research in large retinoblastoma databases is needed to explore the association of tumor characteristics with recurrence and the need for secondary therapeutic interventions.

Establishment and validation of a clinical risk scoring model to predict fatal risk in SFTS hospitalized patients

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection with a high case fatality rate. Significant gaps remain in studies analyzing the clinical characteristics of fatal cases.MethodsFrom January 2017 to June 2023, 427 SFTS cases were included in this study. A total of 67 variables about their demographic, clinical, and laboratory data were collected. Univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) method was used to screen predictors from the cohort. Multivariate logistic regression was used to identify independent predictors and nomograms were developed. Calibration, decision curves and area under the curve (AUC) were used to assess model performance.ResultsThe multivariate logistic regression analysis screened out the four most significant factors, including age > 70 years (p = 0.001, OR = 2.516, 95% CI 1.452–4.360), elevated serum PT (p < 0.001, OR = 1.383, 95% CI 1.143–1.673), high viral load (p < 0. 001, OR = 1.496, 95% CI 1.290–1.735) and high level of serum urea (> 8.0 μmol/L) (p < 0.001, OR = 4.433, 95% CI 1.888–10.409). The AUC of the nomogram based on these four factors was 0.813 (95% CI, 0.758–0.868). The bootstrap resampling internal validation model performed well, and decision curve analysis indicated a high net benefit.ConclusionsThe nomogram based on age, elevated PT, high serum urea level, and high viral load can be used to help early identification of SFTS patients at risk of fatality.

Long-term persistence of diverse clones shapes the transmission landscape of invasive Listeria monocytogenes

BackgroundThe foodborne bacterium Listeria monocytogenes (Lm) causes a range of diseases, from mild gastroenteritis to invasive infections that have high fatality rate in vulnerable individuals. Understanding the population genomic structure of invasive Lm is critical to informing public health interventions and infection control policies that will be most effective especially in local and regional communities.MethodsWe sequenced the whole draft genomes of 936 Lm isolates from human clinical samples obtained in a two-decade active surveillance program across 58 counties in New York State, USA. Samples came mostly from blood and cerebrospinal fluid. We characterized the phylogenetic relationships, population structure, antimicrobial resistance genes, virulence genes, and mobile genetic elements.ResultsThe population is genetically heterogenous, consisting of lineages I–IV, 89 clonal complexes, 200 sequence types, and six known serogroups. In addition to intrinsic antimicrobial resistance genes (fosX, lin, norB, and sul), other resistance genes tetM, tetS, ermG, msrD, and mefA were sparsely distributed in the population. Within each lineage, we identified clusters of isolates with ≤ 20 single nucleotide polymorphisms in the core genome alignment. These clusters may represent isolates that share a most recent common ancestor, e.g., they are derived from the same contamination source or demonstrate evidence of transmission or outbreak. We identified 38 epidemiologically linked clusters of isolates, confirming eight previously reported disease outbreaks and the discovery of cryptic outbreaks and undetected chains of transmission, even in the rarely reported Lm lineage III (ST3171). The presence of animal-associated lineages III and IV may suggest a possible spillover of animal-restricted strains to humans. Many transmissible clones persisted over several years and traversed distant sites across the state.ConclusionsOur findings revealed the bacterial determinants of invasive listeriosis, driven mainly by the diversity of locally circulating lineages, intrinsic and mobile antimicrobial resistance and virulence genes, and persistence across geographical and temporal scales. Our findings will inform public health efforts to reduce the burden of invasive listeriosis, including the design of food safety measures, source traceback, and outbreak detection.

Severe Fever with Thrombocytopenia Syndrome in South Korea, 2016-2021: Clinical Features of Severe Progression and Complications.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection with a high case fatality rate. The serious clinical features need to be further defined. We performed a retrospective analysis among SFTS patients in South Korea during 2016-2021 to update the current status. The basic epidemiology of all reported cases was analyzed, and the detailed clinical data of the subjects were further collected from study hospitals selected in terms of their geographic location and capability of SFTS care. Cases of SFTS were reported across the country and were greatly increased since the initial endemic phase, even under the passive surveillance system. The case fatality rate remained at approximately 16.8%. Coinfections at admission were present in 7.8% of the patients. Major complications included bleeding (15.2%), hemophagocytic lymphohistiocytosis (6.7%), bacteremia or candidemia (4.0%), and invasive pulmonary aspergillosis (1.7%). It took a median 4 days from the onset of illness to hospital admission. Rapid clinical deterioration was observed with a median 1 day for intensive care unit admission, 3 days for mechanical ventilation, 4 days for renal replacement therapy, and 5 days for death, all after the hospitalization. Multivariate analysis showed that the fatality was associated with older age, bacteremia, or candidemia during hospitalization, and the presence of several variables at admission such as fever, altered mentality, aspartate aminotransferase >200 IU/L, serum creatinine level >1.2 mg/dL, and prolonged prothrombin time and activated partial thromboplastin time. Treatment options to improve clinical outcomes are limited, despite best supportive care. Specific treatment is urgently needed to change the fatal course.

Sociopolitical context and COVID-19 fatality rates in OECD countries: a configurational approach

BackgroundThe effectiveness of crisis response can be influenced by various structural, cultural, and functional aspects within a social system. This study uses a configurational approach to identify combinations of sociopolitical conditions that lead to a high case fatality rate (CFR) of COVID-19 in OECD countries.MethodsA Fuzzy set qualitative comparative analysis (QCA) is conducted on a sample of 38 OECD countries. The outcome to be explained is high COVID-19 CFR. The five potentially causal conditions are level of democracy, state capacity, trust in government, health expenditure per capita, and the median age of population. A comprehensive QCA robustness test protocol is applied, which includes sensitivity ranges, fit-oriented robustness, and case-oriented robustness tests.ResultsNone of the causal conditions in both the presence and negation form were found to be necessary for high or low levels of COVID-19 CFR. Two different combinations of sociopolitical conditions were usually sufficient for the occurrence of a high CFR of COVID-19 in OECD countries. Low state capacity and low trust in government are part of both recipes. The entire solution formula covers 84 percent of the outcome. Some countries have been identified as contradictory cases. The explanations for their COVID-19 CFR require more in-depth case studies.ConclusionsFrom a governance perspective, the weakness of government in effectively implementing policies, and the citizens’ lack of confidence in their government, combined with other structural conditions, serve as barriers to mounting an effective response to COVID-19. These findings can support the idea that the effects of social determinants of COVID-19 outcomes are interconnected and reinforcing.

A Critical Assessment of Remdesivir

Abstract: The COVID-19 pandemic that originated in Wuhan city, China, has affected every village in India. This has killed millions of people. This disease involves symptomatic and asymptomatic mutations. The purpose of this review was to assess the effectiveness of remdesivir particularly against SAR-CoV-2 (Coronaviridae family). The relevant works have been studied with respect to the drug's chemistry, mechanism of action, pharmacokinetics, pharmacodynamics, clinical data, and side effects. Remdesivir has been used in many cases of coronavirus-infected patients because it has been proven to possess beneficial effects; however, significant adverse effects have also been reported. Remdesivir has been reported to help in lowering the disease's high fatality rate. However, the WHO has warned against using the medicine because there is no clinical data to support its therapeutic efficacy.

Role of C-reactive Protein and Procalcitonin in Early Diagnostic Accuracy and Their Prognostic Significance in Sepsis.

Sepsis is a serious condition that often results in high fatality rates, particularly in intensive care units (ICUs). Its nonspecific clinical characteristics makes early diagnosis and therapy difficult, despite how critical they are. The use of biomarkers like procalcitonin (PCT) and C-reactive protein (CRP) in the diagnosis and prognosis of sepsis has demonstrated encouraging results. In contrast to PCT, which is highly selective for bacterial infections, CRP is an acute-phase protein that reflects systemic inflammation. This study aimed to assess the diagnostic accuracy and prognostic significance of CRP and PCT in early sepsis detection and outcome prediction. This study was a retrospective cohort study that involved 90 patients in the ICU who met the criteria for sepsis-3. CRP and PCT levels, clinical data, and outcomes were obtained from electronic medical records. The diagnostic accuracy was tested using receiver operating characteristic (ROC) curves, while the prognostic relevance was analyzed by Kaplan-Meier survival analysis and Cox proportional hazards regression. The mean CRP level was 102.3 mg/L and PCT level was 5.4 ng/mL. ROC analysis revealed an area under the curve (AUC) of 0.78 for CRP and 0.82 for PCT, indicating better diagnostic performance for PCT. High levels of CRP and PCT were associated with poorer survival, with median survival times of 18 and 15 days, respectively, for high-level groups. Cox regression identified CRP and PCT as significant predictors of mortality, with hazard ratios of 1.50 and 1.68, respectively. Both CRP and PCT are valuable biomarkers for diagnosing and prognosticating sepsis. PCT, with its higher specificity for bacterial infections, demonstrates superior diagnostic accuracy compared to CRP. Elevated levels of both biomarkers are associated with increased mortality risk, highlighting their potential role in early sepsis management and outcome prediction.

Torsemide as a Primary Choice in Edema Associated with Heart Failure.

Heart failure (HF) is the fastest-growing disease with a higher fatality rate. The most differentiating feature of HF is pulmonary or peripheral edema, which is characterized by a gradient between intravascular and extravascular pressure. Loop diuretics were chosen as the primary treatment for edema associated with HF due to their efficacy and early onset of action. If an oral dose had not been provided, intravenous (IV) administration of torsemide, or equal doses of furosemide and bumetanide, was preferred. However, the key variables for selecting and administering loop diuretics are their pharmacological qualities as well as their clinical efficacy. Torsemide has greater bioavailability, a higher rate of absorption, a longer duration of action, and lesser ototoxicity, making it the primary choice in the management of edematous HF.

An attachment glycoprotein nanoparticle elicits broadly neutralizing antibodies and protects against lethal Nipah virus infection

Nipah virus (NiV) is a zoonotic emergent paramyxovirus that can cause severe encephalitis and respiratory infections in humans, with a high fatality rate ranging from 40% to 75%. Currently, there are no approved human vaccines or antiviral drugs against NiV. Here, we designed a ferritin-based self-assembling nanoparticle displaying the NiV G head domain on the surface (NiV G-ferritin) and assessed immune responses elicited by the soluble NiV G head domain (NiV sG) or NiV G-ferritin. Immunization with NiV G-ferritin or NiV sG conferred complete protection against lethal NiV challenge without detection of viral RNA in Syrian golden hamsters. Compared to NiV sG, NiV G-ferritin induced significantly faster, broader, and higher serum neutralizing responses against three pathogenic henipaviruses (NiV-Malaysia, NiV-Bangladesh, and Hendra virus). Moreover, NiV G-ferritin induced a durable neutralizing immunity in mice as antisera potently inhibited NiV infection even after six months of the third immunization. Additionally, we isolated a panel of 27 NiV G-binding monoclonal antibodies (mAbs) from NiV G-ferritin immunized mice and found that these mAbs targeted four distinct antigenic sites on NiV G head domain with two sites that have not been defined previously. Notably, 25 isolated mAbs have potent neutralizing activity with 50% inhibitory concentrations less than 10 ng/mL against NiV pseudovirus. Collectively, these findings provide new insights into the immunogenicity of NiV G protein and reveal that NiV G-ferritin is a safe and highly effective vaccine candidate against Nipah virus infection.

A Review of Social Issues in Relation to the Rabies Outbreak in Sarawak, Malaysia

This article aims to review studies on social issues, patient management, and preventive behaviors related to the human rabies outbreak in Sarawak. The review analysed 19 documents from databases and 6 newspaper reports. Studies highlighted factors such as population density, seasonal patterns, and contact with dogs as contributing to the risk of rabies. Control efforts focused on dog vaccination and public education. Key epidemiological studies revealed a high case fatality rate and low rates of immediate medical treatment post-exposure. Social issues such as mishandling of patients, lack of federal support, and low public awareness were significant obstacles. Community engagement and interventions, including educational tools and behavioral assessments, were essential for improving rabies control. Health-seeking behavior patterns showed a general lack of prompt action post-exposure, with many patients seeking treatment too late. Prevention strategies emphasized the “One Health” approach, integrating human and animal health surveillance to enhance rabies control. Comprehensive public education, community involvement, and resource allocation are critical to addressing the ongoing challenges of rabies prevention in Sarawak.

The effects of GCRV on various tissues of grass carp (Ctenopharyngodon idella) and identification of differential interferon-stimulating genes (ISGs) through muscle transcriptome analysis

Grass carp hemorrhagic disease is caused by the grass carp reovirus (GCRV). The disease spreads rapidly and has a high fatality rate, which seriously affects grass carp culture. Moreover, the molecular mechanisms underlying grass carp hemorrhagic disease remain unclear. To decipher the effects of GCRV on grass carp tissues, resistant grass carp A (GA) and susceptible grass carp B (GB) were selected through GCRV treatment, and control grass carp C (GC) was also established. The gill, liver, and muscle tissues exhibited different onset symptoms under the influence of GCRV by histological observation. We selected muscle samples with significant differences in symptoms for Illumina RNA sequencing. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes revealed 3512, 3074, and 1853 differentially expressed genes between "GC vs. GB," "GC vs. GA," and "GA vs. GB," respectively. Additionally, 40 differential immune-related genes and 28 differential interferon-stimulating genes (ISGs) related to the interferon (IFN) pathway were identified. The expression of immunogene-related genes of GB and GA, such as MDA5, IL-34, NF-KB, TRIM25, SOCS3, CEBPB, and BCL2, and genes associated with the JAK-STAT signaling pathway, such as IRF4, STAT1, STAT3, JAK 1, and JAK 2, was significantly upregulated. The IFN and JAK-STAT signaling pathways were closely related to anti-GCRV infection. The transcriptome data and predicted immune genes and ISGs in this study provide novel insights into the treatment of GCRV.

Twenty-five years of Nipah outbreaks in Southeast Asia: A persistent threat to global health

ObjectivesNipah virus (NiV), a bat-borne zoonotic pathogen, poses persistent threats to global public health due to severe clinical manifestation and high case fatality rate (CFR). A critical examination of NiV outbreaks is essential for refining strategies and mitigating the impact of future infections. In this study, we provide a concise update on global NiV outbreaks that occurred during the past 25 years. MethodsIn this geospatial study, we conducted an in-depth examination of the epidemiological characteristics of human NiV cases and deaths from 1998 to 2024 through multiple analyses of public data and official reports. ResultsNiV emerged in 1998 in Malaysia during an outbreak among pig farmers. Since then, NiV outbreaks have been documented in five countries of South and Southeast Asia (Bangladesh, India, Malaysia, Philippines, and Singapore). As of May 2024, there have been 754 confirmed human NiV cases with 435 deaths (CFR: 58%) reported in these five countries. Bangladesh records the highest incidence (341 cases and 241 deaths; CFR: 71%) followed by Malaysia (283 cases and 109 deaths; CFR: 39%), India (102 cases and 74 deaths; CFR: 73%), the Philippines (17 cases and nine deaths; CFR: 53%), and Singapore (11 cases and one death; CFR: 9%). ConclusionsThe clinical outcomes of NiV have been underscoring constant global public health threats as no effective therapies and vaccines are available. Strong global understandings, with an eye on developing vaccines and therapeutics, are required to minimize clinical outcomes and future threats of NiV.

Emergence and expansion of carbapenem resistant enterobacterales in the Western Cape Province, South Africa.

Carbapenem resistant Enterobacterales (CRE) have become established as leading pathogens in South African healthcare facilities. The aim of this study is to describe the epidemiology of CRE carriage and clinical infection episodes at healthcare facilities in the Western Cape Province of South Africa (2016-2020), and identify factors associated with mortality in CRE infected patients. We used routine data from the Provincial Health Data Centre to track the emergence of CRE in healthcare facilities in the Western Cape Province of South Africa. We included all CRE episodes (clinical and carriage) at Western Cape hospitals (including day and inpatients) from 2016 to 2020 to determine the distribution of CRE, patient demographics and antibiotic resistance phenotypes. Logistic regression was performed to identify factors associated with mortality from clinical CRE episodes. 2242 CRE episodes (1580 [70.5%] clinical and 662 [29.5%] carriage) were identified. From these, 2281 CRE isolates were identified, with Klebsiella species predominating (1644, 72.1%). Affected patients had a median age of 31 (IQR 0-52) years, and 1167 (52.0%) were male. Most CRE episodes were recorded in central hospitals (70.0%, p < 0.001). Where outcome data was available, crude in-hospital mortality rates were 26.9% (371/1379) for CRE clinical episodes versus 6.4% (41/640) for CRE carriage episodes (p < 0.001). Factors that showed a statistically significant association with in-hospital mortality were female sex [adjusted odd ratio (aOR) 1.40 (95% confidence interval (CI) 1.09-1.560)], adult patients [aOR 1.76 (95% CI 1.20-2.57)], CRE isolation from a sterile specimen [aOR 0.41 (95% CI 0.32-0.53)], and >3 days between hospital admission and specimen collection [aOR 1.56 (95% CI 1.11-2.18)]. CRE episodes at Western Cape healthcare facilities are concentrated at tertiary hospitals, with high case fatality rates in patients with clinical CRE episodes. Infection control interventions must be strengthened to reduce transmission of CRE, and to reduce infection risks.

The Role of ADCY1 in Regulating the Sensitivity of Platinum-Based Chemotherapy in NSCLC.

Lung cancer has the highest fatality rate among malignant tumors in the world. Finding new biomarkers of drug resistance is of great importance in the prognosis of lung cancer patients. We found that the polymorphisms of Adenylate Cyclase 1 (ADCY1) are significantly associated with platinum-based chemotherapy resistance in lung cancer patients in our previous research. In this study, we wanted to identify the mechanism of ADCY1 affecting platinum resistance. We used an MTT assay to find if the expression of ADCY1 is associated with the sensitivity of cisplatin in A549, H1299, and A549-DDP cells. Then, we performed CCK-8 tests to detect the absorbance of these cells stimulated by ADCY1, which can discover the cell proliferation that is affected by ADCY1. We investigated cell apoptosis and cell cycles regulated by ADCY1 through the flow cytometry assay. RNA sequencing was used to find the downstream genes affected by ADCY1 which may be associated with drug resistance in lung cancer patients. ADCY1 has higher expression in lung cancer cells than in normal cells. ADCY1 can affect cisplatin resistance in lung cancer cells by regulating cell proliferation, cell apoptosis, and the cell cycle. It may control cell apoptosis by regulating the classical apoptosis biomarkers Bax and Bcl2. Our study showed that ADCY1 may be a new biomarker in the prognosis of lung cancer patients. Much work remains to be carried out to clarify the mechanism in this important emerging field.

A nomogram including admission serum glycated albumin/albumin ratio to predict mortality in patients with severe fever with thrombocytopenia syndrome

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease with a high fatality rate. Although several nomograms based on demographic and laboratory data have been reported to predict the prognosis of SFTS in recent studies, baseline serum glycated albumin (GA)/albumin (ALB) ratio included risk model has not been evaluated for the prediction of clinical outcome.MethodsA total of 214 SFTS patients with integral data admitted to our hospital from May, 2020 to November, 2022 were included in this study. SFTS infection was confirmed by real time fluorescent quantitative PCR (qRT-PCR). The demographic characteristics, clinical and laboratory data were collected with in 24 h of admission and 1 to 2 days before discharge and were analysed retrospectively.ResultsFiffty-seven patients (26.6%) died. Multivariate logistic regression analysis showed that age, aspartate aminotransferase (AST), blood glucose (GLU), GA/ALB ratio, neutrophil counts (NEU) and lymphocyte percentage (LYM%) were the independent risk factors for mortality. A nomogram by these factors was created using RMS package in the R program. Area under the receiver operating characteristic (ROC) curve (AUC) of this nomogram was 0.88 (95% CI: 0.83, 0.93). This model showed the excellent net benefit, as revealed by the decision curve analysis. GA/ALB ratios were also independent risk factors for poor out clinical come in subgroups of patients with hyperglycemia on admission and with diabetes history. Nomograms were constructed by the independent risk factors in the subgroups. AUCs of the nomograms in the subgroups showed high predictive values for adverse prognosis.ConclusionsGA/ALB ratios were independent risk factors for mortality in all SFTS patients and subgroups of with hyperglycemia on admission and diabetes history. The nomograms including GA/ALB ratio had high predictive value for adverse clinical outcome.The nomograms provide a basis for clinical decision-making for the treatment of SFTS patients in different clinical settings.

Analysing Near-Miss Incidents in Construction: A Systematic Literature Review

The construction sector is notorious for its high rate of fatalities globally. Previous research has established that near-miss incidents act as precursors to accidents. This study aims to identify research gaps in the literature on near-miss events in construction and to define potential directions for future research. The Scopus database serves as the knowledge source for this study. To identify publications on near-miss events, the search field “Article Title, Abstract, Keywords” was utilized with the keywords “construction” and “near miss”. The main research themes were defined based on keyword mapping performed using VOSviewer. Selected publications were assessed for their alignment with the defined research theme. A statistical analysis of the publications and the co-occurrence of keywords was conducted. The authors of the identified publications primarily used statistical analyses, artificial intelligence, employee monitoring, tracking systems, and building information modelling in their research. The conclusions from the literature review indicate a need for further research focused on developing effective predictive models for workplace accidents based on knowledge of near-miss events. This will contribute to a better understanding of the mechanisms leading to accidents and their prevention, ultimately resulting in a significant reduction in accidents in the construction sector.

Relation between vitamin D and COVID-19 in Egyptian patients

BackgroundInsufficient vitamin D (VD) levels have been linked to a higher vulnerability to acute respiratory infections and the severity of COVID-19 sickness.ObjectiveThe purpose of this research is to investigate whether or not there is a connection between the amounts of VD produced by patients from Egypt and the severity of COVID-19, as well as the consequences of the disease.MethodsThis research used a case–control design and included a total of 90 adult patients who had been diagnosed with COVID-19, as well as 90 healthy controls who were matched in terms of age and sex. Patients were classified into mild, moderate, and severe categories according to clinical and radiological criteria. The study included measuring levels of VD and analyzing their relationships with illness severity, inflammatory markers, radiological findings, and outcomes.ResultsCOVID-19 patient(s) had notably reduced levels of serum VD versus the control group (11.78 ± 3.24 ng/mL vs. 20.88 ± 7.76 ng/mL, p < 0.001). Lower VD levels were associated with more severe disease (p < 0.001), dyspnea (p < 0.001), radiological abnormalities (p = 0.001), and higher mortality (p < 0.001). A serum VD level ≤ 14.8 ng/mL could differentiate COVID-19 patients from controls with 86.67% sensitivity and 77.78% specificity (AUC = 0.881).ConclusionsCOVID-19 patients often had a deficiency of VD, which was linked to more severe illness, respiratory issues, aberrant radiological findings, and higher fatality rates. VD levels may be used as a biological surrogate marker to assess the risk and predict the outcome of COVID-19.

In Reply: High Fatality Rates in Pediatric Multisystem Inflammatory Syndrome: A Multicenter Experience From the Epicenter of Brazil’s Coronavirus Pandemic

In Reply: High Fatality Rates in Pediatric Multisystem Inflammatory Syndrome: A Multicenter Experience From the Epicenter of Brazil’s Coronavirus Pandemic

Application and development of TCR-T in tumor therapy

As cancer has gradually become the world's deadliest long-term disease, the impact on the public health has been devastating. Especially the Melanoma which is a cancer with a very high malignant and a high fatality rate. With the emergence of adoptive cell therapy(ACT) based on T Cell Receptor-Gene Engineered T Cells (TCR-T), good results have been obtained in scientific research and clinical fields for a variety of malignant tumors. As TCR-T continues to enter the clinic, the FDA also has approved the first case of TCR-T in 2022, and more and more basic researches and clinical trial projects based on TCR-T are gradually being carried out. However, TCR-T therapy still has some defects, such as non-tumor tissue damage caused by off-target effect and insufficient affinity with tumor tissue. Therefore, the affinity and anti-tumor effectiveness of TCR-T should be improved in multiple aspects, and multi-field cooperation should be carried out to promote the development of basic research, a number of products should be introduced into the clinic, and the intervention of economic means to improve the accessibility of TCR-T. Not only brings the Gospel of cure to patients in the field of solid tumors, but also produces innovation in the field of non-solid tumors.