Lethality Rate Research Articles

Monkeypox and extracellular vesicles interlink: an unexplored chapter.

Dear Editor, Monkeypox is an infectious zoonotic disease which is caused by monkeypox virus. It belongs to the genus Orthopoxvirus and the family Poxviridae. The lethality rate of this disease ranges from 1 to 10%. The first occurrence of this disease was in the Democratic Republic of the Congo, Africa. Monkeypox spreads mainly through direct contact with body fluids, respiratory droplets of infected patients and through animals who act as its reservoir The genome of monkeypox virus is linear, enveloped, and double-stranded DNA1,2. This disease mainly has two phases, the first one is the invasive phase which is characterized mainly by fatigue, sore throat, fever, and myalgia. The second phase is the eruptive phase which is characterized by the clinical symptoms of pustular lesions on the legs, multiple lesions on the penile sulcus and huge ulcerative lesions on the perianal skin3. In the current decade, extracellular vesicles (EVs) have gained much attention due to their ability that leads to intercellular communication by activation of various cell signalling pathways. Tetraspanins are the group of surface EVs protein which involved viral particles associated with targeting cells and fission with the recipient cells via cellular membranes. Virus-derived EVs internal cargo influence the recipient cell activity. Envelop virus and EVs have biologically active cargo transportation ability4. EVs are released for normal or pathological conditions (it may be cancer cells or viral-infected cells). The origin of EVs is different as exosomes develop from the plasma membrane and apoptotic bodies develop during the apoptosis process, microvesicles secrete from the plasma membrane and endoplasmic reticulum (these are three major subpopulations of EVs). EVs regulate host–pathogen cellular communication. Viral-infected cell-derived EVs mediated protein and nucleic acid (DNA, RNA) transportation promote the viral pathogenesis progression5,6. In the context of viral infections, the biological role of EVs might have two opposing effects. EVs can influence recipient cells based boosting viral reproduction on the one hand, or they can prevent viral replication by inducing host immune responses on the other7. In addition, integrating viral proteins can cause nonparticipating immune cells to die, which would contribute to the significant loss of immune cells during the initial phases of viral infection or when the viral load is low. In addition to making immune cells more Susceptible to viral infection, intercellular transfer of viral proteins and viral cell surface receptors by EVs aids in evading the host’s immunological response by reducing lymphocyte synthesis of antibodies8. The aim of the article is to highlighted the EVs’ interrelation with the virus and encourage large-scale virologists to decode the virus and EVs related to several aspect. Ethical approval None. Sources of funding None. Authors’ contribution D.M., B.B., R.D., S.N., and P.S.: conceptualization, study design, and writing. A.D. and S.K.J.: editing and reviewing. Conflicts of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) None. Guarantor Saurabh K. Jha.

African Swine Fever Virus Cysteine Protease pS273R Inhibits Type I Interferon Signaling by Mediating STAT2 Degradation.

African swine fever virus (ASFV) is a large DNA virus that causes African swine fever (ASF), an acute and hemorrhagic disease in pigs with lethality rates of up to 100%. To date, how ASFV efficiently suppress the innate immune response remains enigmatic. In this study, we identified ASFV cysteine protease pS273R as an antagonist of type I interferon (IFN). Overexpression of pS273R inhibited JAK-STAT signaling triggered by type I IFNs. Mechanistically, pS273R interacted with STAT2 and recruited the E3 ubiquitin ligase DCST1, resulting in K48-linked polyubiquitination at K55 of STAT2 and subsequent proteasome-dependent degradation of STAT2. Furthermore, such a function of pS273R in JAK-STAT signaling is not dependent on its protease activity. These findings suggest that ASFV pS273R is important to evade host innate immunity. IMPORTANCE ASF is an acute disease in domestic pigs caused by infection with ASFV. ASF has become a global threat with devastating economic and ecological consequences. To date, there are no commercially available, safe, and efficacious vaccines to prevent ASFV infection. ASFV has evolved a series of strategies to evade host immune responses, facilitating its replication and transmission. Therefore, understanding the immune evasion mechanism of ASFV is helpful for the development of prevention and control measures for ASF. Here, we identified ASFV cysteine protease pS273R as an antagonist of type I IFNs. ASFV pS273R interacted with STAT2 and mediated degradation of STAT2, a transcription factor downstream of type I IFNs that is responsible for induction of various IFN-stimulated genes. pS273R recruited the E3 ubiquitin ligase DCST1 to enhance K48-linked polyubiquitination of STAT2 at K55 in a manner independent of its protease activity. These findings suggest that pS273R is important for ASFV to escape host innate immunity, which sheds new light on the mechanisms of ASFV immune evasion.

Modern principles of diagnostics of acute destructive pancreatitis

The incidence of acute destructive pancreatitis is steadily increasing worldwide and, according to the recent literature, is 300-900 patients/mil per year. The increased lethality rate of acute destructive pancreatitis in recent decades, which according to global statistics, ranges from 5% to 20% depending on the severity of the disease, is a cause for concern. It should be noted that most patients with acute destructive pancreatitis are working-age patients, which significantly increases the socio-economic aspect of the problem and urgently requires an active search for ways to solve it. It has been established that the leading pathogenetic mechanism of acute destructive pancreatitis development is enzymatic autolysis of pancreatic parenchyma by its enzymes with their subsequent release into the bloodstream and damage of other organs.

Multi-objective path planning for mobile robot in nuclear accident environment based on improved ant colony optimization with modified A∗

This paper presents a hybrid algorithm to solve the multi-objective path planning (MOPP) problem for mobile robots in a static nuclear accident environment. The proposed algorithm mimics a real nuclear accident site by modeling the environment with a two-layer cost grid map based on geometric modeling and Monte Carlo calculations. The proposed algorithm consists of two steps. The first step optimizes a path by the hybridization of improved ant colony optimization algorithm-modified A∗ (IACO-A∗) that minimizes path length, cumulative radiation dose and energy consumption. The second module is the high radiation dose rate avoidance strategy integrated with the IACO-A∗ algorithm, which will work when the mobile robots sense the lethal radiation dose rate, avoiding radioactive sources with high dose levels. Simulations have been performed under environments of different complexity to evaluate the efficiency of the proposed algorithm, and the results show that IACO-A∗ has better path quality than ACO and IACO. In addition, a study comparing the proposed IACO-A∗ algorithm and recent path planning (PP) methods in three scenarios has been performed. The simulation results show that the proposed IACO-A∗ algorithm is obviously superior in terms of stability and minimization the total cost of MOPP.

Hsp90 could promote BmNPV proliferation by interacting with Actin-4 and enhance its expression

As a highly infectious pathogen, Bombyx mori nuclear polyhedrosis virus (BmNPV) has a high lethality rate in silkworm. Our previous study have confirmed that Hsp90 plays a positive role in BmNPV proliferation and Hsp90 inhibitor, geldanamycin (GA) can decrease the replication of BmNPV in vitro. However, its molecular mechanism is not fully understood. In the present study, first, we found that GA could inhibit the proliferation of BmNPV in a dose-dependent manner and delay the pathogenesis of BmNPV in vivo possibly by altering the transcript level of genes associated with cell apoptosis and immune pathways. Furthermore, by immunoprecipitation (IP) and mass spectrometry analysis, we identified a series of proteins potentially interacting with Hsp90 including two BmNPV encoded proteins. Subsequently, by Co-IP we confirmed the interaction between BmActin-4 and BmHsp90. Knocking down Bmhsp90 by small interfering RNA inhibited the protein expression level of BmActin-4. Over-expression of Bmactin-4 promoted the replication of BmNPV whereas knockdown of Bmactin-4 suppressed BmNPV replication. In addition, decrease of the transcript level of Bmhsp90 in Bmactin-4 knocking down BmN cells was also detected. Taken together, BmHsp90 can interact with BmActin-4 and promote its expression, thereby promoting BmNPV proliferation. Our findings may enrich the molecular mechanism of Hsp90 for promoting virus proliferation and provide new clues to elucidate the interact mechanism between silkworm and virus.

Evaluation of a mimotope of the Rickettsia outer membrane protein A (OmpA) as an antigen in enzyme-linked immunosorbent assay to detect rickettsiosis in capybaras (Hydrochoerus hydrochaeris), horses (Equus caballus), and opossums (Didelphis sp.).

Rickettsia rickettsii is the etiological agent of Rocky Mountain spotted fever, which is an important tick-borne zoonosis and, in Brazil, it causes Brazilian spotted fever, which has high lethality rate. This study aimed to evaluate a synthetic peptide corresponding to a segment of the outer membrane protein A (OmpA) as an antigen in a serological test for the diagnosis of rickettsial infections. The amino acid sequence of the peptide was selected by predicting B cell epitopes using B Cell Epitope Prediction (Immune Epitope Database and Analysis Resource) and Epitopia and OmpA sequences of Rickettsia rickettsii strain 'Brazil' and Rickettsia parkeri strains 'Maculatum 20' and 'Portsmouth'. A peptide with amino acid sequence common to both Rickettsia species was synthesized and arbitrarily named OmpA-pLMC. To evaluate this peptide in enzyme-linked immunosorbent assay (ELISA), serum samples of capybara (Hydrochoerus hydrochaeris), horse (Equus caballus), and opossum (Didelphis albiventris) that had been previously tested by indirect immunofluorescence assay (IFA) for rickettsial infection were separated into IFA-positive and IFA-negative groups and used in the assay. There were no significant differences in ELISA optical density (OD) values between IFA-positive and IFA-negative groups with horse samples. The mean OD values were significantly higher in the IFA-positive capybara serum samples (IFA-pos vs. IFA-neg = 2.389 ± 0.761 vs. 1.760 ± 0.840). However, receiver operating characteristic (ROC) curve analysis did not show significant diagnostic parameters. On the other hand, 12 out of 14 (85.7%) opossum samples of the IFA-positive group showed reactivity in ELISA, and this was significantly higher than of the IFA-negative group (0.7196 ± 0.440 vs. 0.2318 ± 0.098, respectively; 85.7% sensitivity, 100% specificity). Therefore, our results show that OmpA-pLMC has a potential to be used in immunodiagnostic assays to detect spotted fever group rickettsial infections.

Características clínico-epidemiológicas de pacientes fallecidos por COVID-19 en un hospital de referencia en Paraguay entre enero de 2021 a julio de 2022

Introduction. The COVID-19 pandemic from its beginning until August 13, 2022, has caused 19,478 deaths in Paraguay with a fatality rate of 2.78%. The objective of the study is to compare the characteristics of patients who died from COVID-19 in two years, January-December 2021 and January-July 2022. Material and Method. A retrospective cross-sectional analytical study of adult and pediatric patients who died from COVID-19 hospitalized in the respiratory area of the hospital. The patients were confirmed by RT-PCR in nasopharyngeal swabs. Results. Out of 5265 patients hospitalized with COVID-19, 1512 died, yielding an overall lethality rate of 28.7%, in 2021 was 26.3% (1164/4423) and 41.3% (348/842) in 2022. There was a higher percentage of men (53, 6%) among the deceased, significantly higher (p=0.045) in 2022 (58.3%) than in 2021 (52.2%); 69% of the deceased were over 60 years of age in 2022 and 48.3% in 2021; 79.2% of the patients had some risk factor, significantly higher in 2022 (84.3%) than in 2021 (77.7%), especially in AHT (54.3% vs 42.2%), heart disease (15.8% vs 9.7%), CKD (14.4% vs 5.4%), COPD (11.5% vs 5.4%), immunodeficiency (6.3% vs 2.5%) and neurological disease (3.4% vs 1.5%). The need for MRA was significantly (p <0.001) higher in 2022 (50.3%) than in 2021 (31.1%). Conclusion. A high global lethality rate was observed in a reference hospital in Paraguay with mortality predictors similar to those reported worldwide.

Heat shock protein 27 deficiency promotes ferrous ion absorption and enhances acyl-Coenzyme A synthetase long-chain family member 4 stability to promote glioblastoma cell ferroptosis

BackgroundGlioblastoma is one of the malignant tumors of the central nervous system with high lethality, high disability and low survival rate. Effective induction of its death is one of the existing challenges. In recent studies, heat shock protein 27 (HSP27) has been shown to be associated with ferroptosis; therefore, targeting HSP27 may be a potential therapeutic approach for GBM.MethodsImmunohistochemistry and western blot analysis were used to detect the expression of HSP27 in GBM tissues. CCK8, plate clone formation assay, EdU proliferation assay for cell proliferation ability, PI, LDH release assay for cell viability. Reactive oxygen, iron levels, and mitochondrial potential for HSP27 silencing were assayed for ferrotosis in vitro. Western blotting and IP were used to verify the relationship between HSP27 and ACSL4. The effect of knockdown of HSP27 on tumor growth capacity was assessed in an intracranial xenograft model.ResultsHSP27 was significantly highly expressed in GBM. In vitro experiments, knockdown of HSP27 significantly induced ferroptosis in GBM cells. IP and western blot demonstrated a sumo-ization link between HSP27 and ACSL4. In vivo experiments, HSP27 deficiency retarded tumor growth rate by promoting ferroptosis.ConclusionsHSP27 deficiency promotes GBM ferroptosis. Targeting HSP27 may serve as a new direction for GBM treatment.

Design, Synthesis, Fungicidal and Insecticidal Activities of Novel Diamide Compounds Combining Pyrazolyl and Polyfluoro-Substituted Phenyl into Alanine or 2-Aminobutyric Acid Skeletons

Thirty novel diamide compounds combining pyrazolyl and polyfluoro-substituted phenyl groups into alanine or 2-aminobutyric acid skeletons were designed and synthesized with pyflubumide as the lead compound to develop potent and environmentally friendly pesticides. The preliminary bioassay results indicated that the new compounds containing the para-hexa/heptafluoroisopropylphenyl moiety exhibit fungicidal, insecticidal, and acaricidal activities. This is the first time that the para-hexa/heptafluoroisopropylphenyl group is a key fragment of the fungicidal activity of new N-phenyl amide compounds. Most of the target compounds exhibited moderate to good insecticidal activity against Aphis craccivora at a concentration of 400 μg/mL, and some showed moderate activity at a concentration of 200 μg/mL; in particular, compounds I-4, II-a-10, and III-26 displayed higher than 78% lethal rates at 200 μg/mL. Compound II-a-14 exhibited a 61.1% inhibition at 200 μg/mL for Tetranychus cinnabarinus. In addition, some of the target compounds exhibited good insecticidal activities against Plutella xylostella at a concentration of 200 μg/mL; the mortalities of compounds I-1, and II-a-15 were 76.7% and 70.0%, respectively. Preliminary analysis of the structure-activity relationship (SAR) indicated that the insecticidal and acaricidal activities varied significantly depending on the type of substituent and substitution pattern. The fungicidal activity results showed that compounds I-1, II-a-10, II-a-17, and III-26 exhibited good antifungal effects. Enzymatic activity experiments and in vivo efficacy of compound II-a-10 were conducted and discussed.

IMPACT OF STATINS ON THE CLINICAL COURSE OF COVID-19-ASSOCIATED PNEUMONIA IN UNVACCINATED PATIENTS WITH ARTERIAL HYPERTENSION

The aim: To assess the impact of statins on the severity and lethality rate in hypertensive patients with COVID-19-associated pneumonia. Materials and methods: 106 unvaccinated hypertensive patients were enrolled in the study. 29 (27.4%) patients took statins. Results: Statins were not associated with reduced risks of lethality (relative risk (RR), 0.24; [95%CI, 0.03-1.79], p=0.16), decline in oxygen saturation <92% during the inpatient stay (RR, 0.70 [95%CI, 0.39-1.28], p=0.25) and need for supplemental oxygen (RR, 0.84; [95%CI, 0.51-1.37], p=0.48). There was no significant difference in the median length of in-hospital stay between the patients taking statins (14.0 [10.0-15.0] days) and patients, which didn't take statins (13.0 [9.0-18.0] days) (p=0.76). However, subgroup analysis showed that statins reduced the risk of decline in oxygen saturation <92% in patients aged 65 years and older with body mass index $ 25.0 kg/m2 (RR, 0.33 [95%CI, 0.11-0.92], p=0.03). Conclusions: Statins didn't a#ect the severity and lethality rate in hypertensive patients with COVID-19-associated pneumonia. Subgroup analysis showed that statin use was associated with a decrease in morbidity of patients aged 65 years and older with BMI $25.0 kg/m2 hospitalized for COVID-19-associated pneumonia.

ОБЩАЯ ХАРАКТЕРИСТИКА КЛИНИЧЕСКИХ НАБЛЮДЕНИЙ ОСТРОГО ПАНКРЕАТИТА БИЛИАРНОЙ ЭТИОЛОГИИ

The dynamics of hospital morbidity and lethality rate in acute biliary pancrea-titis are analyzed; demographic regularities of acute biliary pancreatitis morbidity are determined; general characteristics of clinical observations are presented. The increase in the absolute number of patients with acute pancreatitis of bili-ary etiology and necrotic pancreatitis of biliary etiology in many respects deter-mines the growth of acute pancreatitis morbidity in general. The morbidity of acute pancreatitis of biliary etiology is almost evenly distrib-uted between men and women with the ratio 1,4:1. The peak of morbidity (36,1 %) falls on elderly age. In the age structure of acute biliary pancreatitis the share of elderly and senile age was 62,6 %. Every third patient sought medical help during the first 12 hours, 64,4 % – during the first 24 hours, 78,1 % – dur-ing the first 48 hours of the disease onset. The category of patients with the high-est proportion (14,2 %) were elderly men, who came for treatment in the first 24 hours after the onset of the disease. In 82,7 % of patients with acute biliary pancreatitis the premorbid status was aggravated by two or more concomitant diseases, every 5th patient had CHD manifested by angina pectoris, postinfarction cardiosclerosis or rhythm disturb-ances. Premorbid status has a significant influence on the overall mortality in acute pancreatitis of biliary etiology. The relapses of acute pancreatitis of biliary etiology make up 9,6 % of all the attacks of the disease and 25,3 % of all relapses of acute pancreatitis, and in 47,6 % of cases of recurrent acute pancreatitis of biliary etiology the disease has an equally or more severe course with possible lethal outcome.

Hospitalizations and deaths of children and adolescents with Severe Acute Respiratory Infection due to COVID-19 during the epidemiological year of 2020.

This study aimed to analyze the profile of hospitalizations and factors associated with the deaths of children and adolescents with severe acute respiratory infection (SARI) caused by SARS-CoV-2 nationwide. The study comprised 6,843 children and adolescents hospitalized in 2020 who tested positive for COVID-19, based on data from the Influenza Epidemiological Surveillance Information System. Sociodemographic and clinical profiles, hospitalization frequency, lethality and recovery rates were analyzed. The outcome was recovery or death. The 6,843 children and adolescents comprised 1.9% of SARI hospitalized cases (n = 563,051). Of these, 57.7% developed critical SARI and 90% survived. Comorbidities were present in 40.8%, especially asthma, immunodepression, and neurological and cardiovascular diseases. The main symptoms were fever, cough, dyspnea, respiratory distress, and low oxygen saturation. Among those with critical SARI, 91.4% died. There was a higher frequency of children, especially those under five years of age and of mixed ethnicity. The highest hospitalization frequency occurred in the Southeastern and Northeastern regions, the highest recovery rates in the Southeastern and Southern regions, and the highest lethality rates in the Northern and Northeastern regions. Deaths were associated with ages ranging from 12 to 19 and being under one year of age, living in the Northern and Northeastern regions, progression to critical SARI, and having immunosuppression and cardiovascular disease. In contrast, asthma was associated with lower death rates. The frequency of complications and mortality rates caused by SARS-Cov-2 in the pediatric population are relevant, as well as the severity of the epidemic in the social inequality context and the health services' frailty.

ОСТРЫЙ ПАНКРЕАТИТ БИЛИАРНОЙ ЭТИОЛОГИИ. Сообщение 1. ЭПИДЕМИОЛОГИЯ И СОВРЕМЕННЫЕ ПРЕДСТАВЛЕНИЯ О ПАТОГЕНЕЗЕ

The epidemiological data and modern ideas concerning the pathogenesis of acute biliary pancreatitis are presented. Acute pancreatitis of biliary etiology is a widespread pathology with the lethality rate of 2–7%, and at a severe course – 17–39%. The leading pathogenetic mechanism of acute pancreatitis of biliary etiology is pancreaticobiliary ductal hypertesion. During the conservative treatment the relapse rate of acute biliary pancreatitis reaches 90% with the lethality rate up to 31%. The only risk factor of the relapse development is refusal to perform cholecystectomy after the first attack of acute biliary pancreatitis to the patients whose condition permitted to survive the intervention.

Metabolic primary liver cancer in adults: risk factors and pathogenic mechanisms

Primary liver cancer (PLC) is a heterogeneous group of disorders arising with the background of chronic liver disease (CLD) owing to varying etiologies. PLC carries a high lethality rate and a substantial epidemiological, clinical, and financial burden, which is projected to escalate. The two most common PLC histotypes in adults are hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC); the latter is sub-classified as either intrahepatic CC or extrahepatic CC. Over recent decades, there has been a decline of viral CLD accompanied by an increase in dysmetabolic CLD, resulting in PLC becoming relatively more common in Western countries. Metabolic co-morbidities are risk factors and co-factors for HCC and (increasingly) CC. Complex immunological, cellular, pro-inflammatory, molecular, and genetic processes in the systemic dysmetabolic milieu increase PLC risk. Improved understanding of these mechanisms requires close surveillance and early diagnosis of at-risk patients while paving the way for personalized medicine, chemoprevention, and innovative management of metabolic PLC.

Infestação natural por carrapatos como causa de morte em bovinos de corte

ABSTRACT: Although infestation by Rhipicephalus microplus is mentioned as the cause of death among cattle, there are only studies with artificial infestations in which intense parasitism led to the death of cattle due to severe anemia. This study seems to be the first to describe the epidemiology, clinical-pathological condition, and diagnostic conduct of infestation by R. microplus as the cause of death of European breed calves introduced in shady, enclosed pastures in regions with rainfall prior to the onset of the outbreak. The affected calves presented apathy, anorexia, and anemia and were severely infested by R. microplus. The lethality rate of the outbreak was 36.5%. After the rainy period, the dry season facilitated a decrease in the nutritional status of the affected cattle. The delay in the definitive diagnosis contributed to the economic loss of the farm due to the cost of erroneous treatments and the number of dead cattle. The main factors that contributed to the deaths were climatic, environmental, and individual. This study demonstrates that severe infestations by R. microplus in low-quality pasture-raised calves are fatal and emphasizes the importance of diagnostic tools to reduce the economic loss caused by death due to infestation by ticks.

Hospitalizations and deaths of Brazilian children and adolescents with Severe Acute Respiratory Syndrome caused by COVID-19.

Since the onset of the pandemic, COVID-19 has affected the entire world population, however, data on child morbidity and mortality are scarce. This study aimed to analyze the profile of hospitalizations and factors associated with the deaths of Brazilian children and adolescents with Severe Acute Respiratory Syndrome caused by COVID-19. This cross-sectional study uses public domain data from the Influenza Epidemiological Surveillance System in 2021. The prevalence rates, lethality, and duration of hospitalization of children and adolescents with Severe Acute Respiratory Syndrome caused by COVID-19 were analyzed. Logistic regression and adjusted Odds Ratio were used. A p < 0.05 was considered significant. The prevalence of hospitalization among children and adolescents was 3.6%, and the case lethality rate was 4.0%. Higher lethality rates occurred among adolescents, natives, rural residents, those living in Brazil's northern and northeastern regions, and those who became critically ill and had comorbidities. Hospitalization time was longer for adolescents who became critically ill or had comorbidities. The highest chance of death was associated with: children under one year of age and adolescents, natives, and residents from the North, Northeast, and Southeast regions, who became critically ill and had comorbidities. Despite lower hospitalization and death rates than adults, the prevalence, complications, and mortality from COVID-19 in the pediatric population are relevant. Knowledge of the profile of children and adolescents hospitalized due to COVID-19 and the factors associated with these deaths allows the guidance of response efforts directed to assist this vulnerable population.

MAC-ResNet: Knowledge Distillation Based Lightweight Multiscale-Attention-Crop-ResNet for Eyelid Tumors Detection and Classification.

Eyelid tumors are tumors that occur in the eye and its appendages, affecting vision and appearance, causing blindness and disability, and some having a high lethality rate. Pathological images of eyelid tumors are characterized by large pixels, multiple scales, and similar features. Solving the problem of difficult and time-consuming fine-grained classification of pathological images is important to improve the efficiency and quality of pathological diagnosis. The morphology of Basal Cell Carcinoma (BCC), Meibomian Gland Carcinoma (MGC), and Cutaneous Melanoma (CM) in eyelid tumors are very similar, and it is easy to be misdiagnosed among each category. In addition, the diseased area, which is decisive for the diagnosis of the disease, usually occupies only a relatively minor portion of the entire pathology section, and screening the area of interest is a tedious and time-consuming task. In this paper, deep learning techniques to investigate the pathological images of eyelid tumors. Inspired by the knowledge distillation process, we propose the Multiscale-Attention-Crop-ResNet (MAC-ResNet) network model to achieve the automatic classification of three malignant tumors and the automatic localization of whole slide imaging (WSI) lesion regions using U-Net. The final accuracy rates of the three classification problems of eyelid tumors on MAC-ResNet were 96.8%, 94.6%, and 90.8%, respectively.

Cadmium chloride exposure impairs the growth and behavior of Drosophila via ferroptosis

Cadmium (Cd) is a widely distributed toxic heavy metal that enters the environment via anthropogenic mobilization and accumulates in plants and animals, causing metabolic abnormalities even mortality. Although the toxic effects and stress damage of cadmium have been investigated extensively over the past few decades, research on its ability to trigger ferroptosis, growth retardation, and behavioral abnormalities is insufficient. As a result, the effects of CdCl2 exposure on growth and development, activity and sleep, and ferroptosis in this study were examined in fruit fly (Drosophila melanogaster). When exposed to 0.5 mM CdCl2, the entire growth period from larvae to adults was prolonged, and the rates of pupation and eclosion were decreased. Additionally, CdCl2 exposure resulted in a decrease in body weight and individual size of fruit fly and high lethality rate. Moreover, CdCl2 exposure altered fruit fly behavior, including decreased activity and increased sleep duration, particularly in females. Ferrostatin-1 (Fer-1) is a potent selective ferroptosis inhibitor that effectively slows lipid hydroperoxide accumulation to rescue body size reduction and restore activity and sleep in CdCl2-exposed female flies. CdCl2 exposure could induce ferroptosis in fruit fly mechanistically, as evidenced by inhibition of Nrf2 signaling pathway, accumulation of lipid peroxidation, impairment of GPX4 antioxidant system, and upregulation of iron metabolism. Our findings suggest that Cd exposure triggers ferroptosis, which leads to growth retardation and behavioral disorders in fruit fly.

Bacterial identification in cerebrospinal fluid of domestic species with neurologic signs: a retrospective case-series study in 136 animals (2005-2021).

Central nervous system (CNS) infections comprise life-threatening clinical conditions in domestic species, and are commonly related to severe sequelae, disability, or high fatality rates. A set of bacterial pathogens have been identified in central nervous infections in livestock and companion animals, although the most of descriptions are restricted to case reports and a lack of comprehensive studies involving CNS-related bacterial infections have been focused on a great number of domestic species. In this scenario, we retrospectively investigated selected epidemiological data, clinical findings, bacteriological culture, and in vitro susceptibility patterns of 136 nonrepetitive neurologic cases in domestic species (2005-2021). Bacterial isolates were recovered from 25% (34/136) of the cerebrospinal fluid (CSF) sampled. The isolates were obtained from cattle (9/136 = 6.6%), dogs (7/136 = 5.1%), horses (6/136 = 4.4%), goats (3/136 = 2.2%), pigs (3/136 = 2.2%), sheep (3/136 = 2.2%), cats (2/136 = 1.5%), and asinine (1/136 = 0.7%). Among animals with bacterial isolation, Staphylococcus aureus (6/34 = 17.6%), Escherichia coli (5/34 = 14.7%), Staphylococcus beta-hemolytic (5/34 = 14.7%), and Trueperella pyogenes (3/34 = 8.8%) were predominant, in addition to a miscellaneous of other bacteria isolated in minor frequency, e.g., Corynebacterium pseudotuberculosis, Enterobacter cloacae, Mannheimia haemolytica, Pseudomonas aeruginosa, and Streptococcus equi subsp. equi. In vitro susceptibility tests of isolates revealed that amoxicillin/clavulanic acid (11/13 = 84.6%), cephalexin (9/11 = 81.8%), and florfenicol (9/12 = 75%) were the most effective antimicrobials. Conversely, isolates exhibited resistance mainly to tetracycline (6/10 = 60%), penicillin (6/11 = 54.5%), and trimethoprim/sulfamethoxazole (5/11 = 45.5%). Also, multidrug resistance to ≥ 3 classes of antimicrobials was found in 23.5% (8/34) strains. Data relative to the outcome was available in 79.4% (27/34) of animals that had bacterial isolation, and from these, the lethality rate was 92.6% (25/27). Incoordination (14/34 = 41.2%), recumbency (11/34 = 32.4%), apathy (10/34 = 29.4%), anorexia (9/34 = 26.5%), blindness (7/34 = 20.6%), seizure (6/34 = 17.6%), limb paresis (5/34 = 14.7%), head-pressing (4/34 = 11.8%), and nystagmus (3/34 = 8.8%) were the most frequent clinical signs. A variety of bacterial pathogens were identified in the CSF of domestic species showing neurologic signs, with a predominance of staphylococci, streptococci, and enterobacteria. High lethality of cases, poor in vitro efficacy of conventional antimicrobials, and a high in vitro multidrug resistance pattern of isolates were seen. Our results contribute to etiological characterization, antimicrobial resistance patterns, and clinical-epidemiological findings of bacterial infections in domestic species with neurological signs.

Oncolytic HSV-1 suppresses cell invasion through downregulating Sp1 in experimental glioblastoma

Gliomas are highly aggressive intracranial tumors that are difficult to resect and have high lethality and recurrence rates. According to WHO grading criteria, glioblastoma with wild-type IDH1 has a poorer prognosis than WHO grade 4 IDH-mutant astrocytomas. To date, no effective therapeutic strategies have been developed to treat glioblastoma. Clinical trials have shown that herpes simplex virus (HSV)-1 is the safest and most efficacious oncolytic virus against glioblastoma, but the molecular antitumor mechanism of action of HSV-1 has not yet been determined. Deletion of the γ34.5 and ICP47 genes from a strain of HSV-1 yielded the oncolytic virus, oHSV-1, which reduced glioma cell viability, migration, and invasive capacity, as well as the growth of microvilli. Infected cell polypeptide 4 (ICP4) expressed by oHSV-1 was found to suppress the expression of the transcription factor Sp1, reducing the expression of host invasion-related genes. In vivo, oHSV-1 showed significant antitumor effects by suppressing the expression of Sp1 and invasion-associated genes, highly expressed in high-grade glioblastoma tissue specimens. These findings indicate that Sp1 may be a molecular marker predicting the antitumor effects of oHSV-1 in the treatment of glioma and that oHSV-1 suppresses host cell invasion through the ICP4-mediated downregulation of Sp1.