A novel approach to Parkinson's disease treatment with a potentially dual-acting therapeutic agent that targetsα-synuclein aggregation and neuron death

Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy bodies.While the current standards of therapy have been successful in providing some symptom relief,they fail to address the underlying pathophysiology of PD and as a result,they have no effect on disease progression.

Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy

Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.

Beyond authorship: Analyzing contributions in PLOS ONE and the challenges of appropriate attribution

Purpose:This study aims to evaluate the accuracy of authorship attributions in scientific publications,focusing on the fairness and precision of individual contributions within academic works.Design/methodology/approach:The study analyzes 81,823 publications from the journal PLOS ONE,covering the period from January 2018 to June 2023.It examines the authorship attributions within these publications to try and determine the prevalence of inappropriate authorship.It also investigates the demographic and professional profiles of affected authors,exploring trends and potential factors contributing to inaccuracies in authorship.Findings:Surprisingly,9.14%of articles feature at least one author with inappropriate authorship,affecting over 14,000 individuals(2.56%of the sample).Inappropriate authorship is more concentrated in Asia,Africa,and specific European countries like Italy.Established researchers with significant publication records and those affiliated with companies or nonprofits show higher instances of potential monetary authorship.Research limitations:Our findings are based on contributions as declared by the authors,which implies a degree of trust in their transparency.However,this reliance on self-reporting may introduce biases or inaccuracies into the dataset.Further research could employ additional verification methods to enhance the reliability of the findings.Practical implications:These findings have significant implications for journal publishers,Beyond authorship:Analyzing contributions in PLOS ONE and Maddi,A.,&the challenges of appropriate attribution highlighting the necessity for robust control mechanisms to ensure the integrity of authorship attributions.Moreover,researchers must exercise discernment in determining when to acknowledge a contributor and when to include them in the author list.Addressing these issues is crucial for maintaining the credibility and fairness of academic publications.Originality/value:This study contributes to an understanding of critical issues within academic authorship,shedding light on the prevalence and impact of inappropriate authorship attributions.By calling for a nuanced approach to ensure accurate credit is given where it is due,the study underscores the importance of upholding ethical standards in scholarly publishing.

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Risk factors for early death in severe non-brain- injured trauma patients

Severe trauma is one of the main causes of premature death,posing a significant challenge to public health systems.[1]At present,there is a lack of universally accepted guidelines for rapid detection of life-threatening severe trauma,[2]and the accuracy of existing prognostic models in predicting early death is limited.[3,4]Severe non-brain-injured trauma(SNT)patients account for approximately 70%of all trauma-related deaths.Moreover,there is a lack of studies on early death in SNT patients.[5]This study aims to identify risk factors associated with early death(≤72 h post-admission)in SNT patients.

Intertwined depressive and cognitive trajectories and the risk of dementia and death in older adults:a competing risk analysis

Background Depressive symptoms and cognitive impairment often interact,rendering their associations controversial.To date,their joint trajectories and associations with dementia and death remain underexplored.Aims To explore the interactions between depressive symptoms and cognitive function,their developmental trajectories and the associations with all-cause dementia,Alzheimer’s disease(AD)and all-cause death in older adults.Methods Data were from the Health and Retirement Study.Depressive symptoms and cognitive function were measured using the 8-item Centre for Epidemiologic Studies Depression Scale and the Telephone Interview of Cognitive Status,respectively.All-cause dementia and AD were defined by self-reported or proxy-reported physician diagnoses.All-cause death was determined by interviews.The restricted cubic spline,group-based trajectory modelling and subdistribution hazard regression were used.Results Significant interactions between depressive symptoms and cognitive function in 2010 in their association with new-onset all-cause dementia and AD from 2010 to 2020 were found,especially in women(p for interaction<0.05).Independent trajectory analysis showed that emerging or high(vs no)depressive trajectories and poor or rapidly decreased cognitive trajectories(vs very good)from 1996 to 2010 were at significantly higher risk of subsequent all-cause dementia,AD and all-cause death.15 joint trajectories of depressive symptoms and cognitive function from 1996 to 2010 were determined,where rapidly decreased cognitive function was more common in those with no depressive symptoms.Compared with older adults with the trajectory of no depressive symptoms and very good cognitive function,those with the trajectory of no depressive symptoms but rapidly decreased cognitive function were much more likely to develop new-onset all-cause dementia and death,with subdistribution hazard ratios(95%confidence intervals)of 4.47(2.99 to 6.67)and 1.84(1.43 to 2.36),especially in women.Conclusions To effectively mitigate the risk of dementia and death,it is crucial to acknowledge the importance of preventing cognitive decline in older adults without depressive symptoms,particularly in women.

Attributable liver cancer deaths and disability-adjusted life years in China and worldwide: profiles and changing trends

Objective: Liver cancer is a major health concern globally and in China. This analysis investigated deaths and disability-adjusted life years(DALYs) with respect to etiologies and risk factors for liver cancer in China and worldwide.Methods: Global and China-specific data were collected on liver cancer deaths, DALYs, and age-standardized rates(ASRs) from the Global Burden of Disease Study 2019 database. Liver cancer etiologies were classified into five groups and risk factors were categorized into three levels. Each proportion of liver cancer burden was calculated in different geographic regions. The joinpoint regression model were used to assess the trends from 1990±2019.Results: Liver cancer accounted for 484,577 deaths worldwide in 2019 with an ASR of 5.9 per 100,000 population. China had an elevated liver cancer death ASR in 2019 and males had an ASR 1.7 times the global rate. The global ASR for DALYs peaked at 75±79 years of age but peaked earlier in China. Hepatitis B virus was the prominent etiology globally(39.5%) and in China(62.5%), followed by hepatitis C virus and alcohol consumption. In high sociodemographic index countries, non-alcoholic steatohepatitis has gained an increasing contribution as an etiologic factor. The liver cancer burden due to various etiologies has decreased globally in both genders. However, metabolic risk factors, particularly obesity, have had a growing contribution to the liver cancer burden, especially among males.Conclusions: Despite an overall decreasing trend in the liver cancer burden in China and worldwide, there has been a rising contribution from metabolic risk factors, highlighting the importance of implementing targeted prevention and control strategies that address regional and gender disparities.

Guide for Authors

Introduction Types ofpaper Contributions falling into the following categories will be considered for publication:Reviews,Technical papers,Theoretical papers,and Editorial.Please ensure that you select the appropriate article type from the list of options when making your submission.Authors contributing to special issues should ensure that they select the special issue article type from this list.

Information for Authors

Chinese Phaysics Letters(CPL)is a peer-reviewed,inter-national and multidisciplinary journal sponsored by the Chi-nese Phaysical Society(CPS)and Institute of Physics,CAS,and hosted online by IOP Publishing Ltd.Launched in 1984 asthe flagship journal of CPS,CPL has become one of the mostprestigious periodicals published in China,and been among thegood choices for worldwide physicists to disseminate their mostimportant breakthroughs.

Audits of Death in HIV-Infected Children and Adolescents Followed up in the Pediatric Department of the Regional Teaching Hospital of Borgou/Alibori from 2005 to 2020

Introduction: Human immunodeficiency virus (HIV) is a major public health problem with high morbidity and mortality among children. The objective of this work was to audit the deaths of children and adolescents with HIV infection followed up in the pediatric department of the Regional Teaching Hospital of Borgou/Alibori (CHUDB/A) the from 2005 to 2020. Patients and Method: This was a retrospective and descriptive study conducted in the pediatric department of CHUD/B-A in Parakou. All children with HIV infection who died from January 1, 2005 to August 31, 2020 were included. Data collection was carried out in three stages: a phase of medical records processing, a phase of community survey and a phase of death audits. The variables studied were sociodemographic, clinical, biological, therapeutic and evolutionary. Results: Over the study period, the data of 464 infected children were recorded, including 92 deaths, representing a case fatality rate of 19.83%. Severe acute malnutrition (69.23%), gastro-intestinal tract infections (43.58%) and serious opportunistic pulmonary infections (24.36% pulmonary tuberculosis and 19.23% pneumocystis) were the main causes of death. The main dysfunctions found were: the delayed diagnosis of HIV infection (79.35%), the absence or delay in consultation when the child’s clinical condition deteriorates (32.61% and 47.83%), delayed initiation of antiretroviral treatment (42.39%) and non-adherence to treatment (38.04%). Non-adherence to treatment was predominant in adolescents (90.49%). Conclusion: Specific interventions for early detection, adequate nutritional care, psychosocial support for adolescents and mothers of children are necessary to reduce mortality due to HIV among children and adolescents.

Effects of Maternal Death on Children Living in the Sagnarigu Municipality

Introduction: The greatest effect of maternal mortality is renowned in children aged 2 - 5 months whose mothers had died. Children whose mothers died due to maternal complications were likely to record a higher mortality in infancy compared to children of surviving mothers. Motherless children mostly suffer a lot due to lack of day-to-day care, isolation, lack of motivation as well as economic cost associated with mother’s death. Thus, the purpose of this study was to ascertain the lives of children whose mothers passed away during childbirth at the Sagnarigu Municipality. Methods: This quantitative cross-sectional study was carried out at the Sagnarigu Municipal. The study recruited 297 respondents. To assess the effects of maternal death on the lives of children, families that experienced maternal death were assessed. The number of pregnancies experienced by the deceased woman, pregnancy-related complaints experienced, determinants of maternal death, number of children alive, and their standard of living were assessed with the aid of a structured questionnaire. Results: The data showed that negligence, illiteracy, poor road access, poverty, ignorance, delays in recognizing the problem, delays in making appropriate decisions, delays in the health facility, delays in giving the appropriate treatments, and traditional beliefs were some of the factors that led to maternal death in the Sagnarigu Municipality. Conclusion: The study concluded that determinants of maternal death in the Sagnarigu Municipal included the following;negligence, illiteracy, poverty, and delays in recognizing the problem. The study findings also demonstrated that the effects of maternal death on children are diverse and cut across different areas of a child’s life including livelihood sustenance, healthcare, education, and emotional and psychological development.

Information for Authors

General Journal of Beijing Institute of Technology(JBIT)is a periodical publication on science and technology published by Beijing Institute of Technology under the sponsorship of the Ministry of Industry and Information Technology of the People's Republic of China.JBIT was inaugurated in 1992.

Information for Authors

General Journal of Bejing Institute of Technology(JBIT)is a periodical publication on science andtechnology published by Beijing Institute of Technology under the sponsorship of the Ministry ofIndustry and Information Technology of the People's Republic of China.JBIT was inaugurated in 1992.

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity.At embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction.The LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three dosages.Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS group.Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS group.Quercetin significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS induction.Quercetin significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of AMPKα1,LC3-I,and LC3-II.Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy,programmed cell death,and myocardiocytes permeability.

Information for Authors

General Journal of Bejing Institute of Technology(JBIT)is a periodical publication on science andtechnology published by Beijing Institute of Technology under the sponsorship of the Ministry ofIndustry and Information Technology of the People's Republic of China.JBIT was inaugurated in 1992.

Epidemiological Aspects of Stillbirth and Neonatal Deaths in the Delivery Room at the Libreville Mother-Child University Hospital from 2019 to 2022

Introduction: Stillbirths are estimated at 2 million each year, of which more than 40% occur during labour. Our objective was to study the epidemiological aspects of stillbirth and neonatal deaths in the delivery room in our health facility. Patients and methods: Prospective, descriptive and analytical study, conducted at the Jeanne Ebori Foundation Mother-Child University Hospital over 4 years (January 2019-December 2022). All neonatal deaths in the delivery room or foetal death in utero, were included. Results: Among the 18,346 deliveries performed, 512 newborns were declared dead in the delivery room (27.9‰ live births), divided into in utero foetal death (19.0‰) and immediate neonatal death (8.9‰). The mean age was 34.3 weeks of amenorrhea. The rate of preterm birth was 60.4%. The sex ratio was 1.1. The average weight was 2186.6. The main causes were vascular (46.1%), foetal (20.2%), adnexal (17.1%) and asphyxia per partum (16.6%). Foetal causes were more likely to result in IUFD than other causes (OR = 6.4 [2.4 - 15.7], p < 0.001). After birth, partum asphyxia was more likely to lead to death before 15 minutes of life than other causes (OR = 11 [6.1 - 18.9], p Conclusion: The causes of stillbirth and early neonatal mortality are dominated by maternal vascular pathologies. However, the proportion of childbirth-related causes remains worrying. Better monitoring of pregnancy and labour will minimize this prevalence in our hospital.

Effect of the Implementation of Emonc in the Reduction of Maternal Deaths in the Department of Collines from 2018 to 2022

Background: Maternal and neonatal mortality remains a public health problem in Benin. Each year, approximately 1500 maternal deaths and more than 12,000 newborn deaths are recorded there. In order to correct the situation, strategies such as the implementation of Emergency Obstetric and Neonatal Care (EmONC) were initiated. Objective: Determine the rates of maternal deaths in EmONC centers in the Collines department from 2018 to 2022. Framework and Methods: The study took place in Benin precisely in the Collines department. This was a descriptive cross-sectional study. Data collection was carried out during the first two weeks of January 2023 and covered data from the 09 Basic Emergency Obstetric and Neonatal Care centers (BEMONC) and the Obstetric and Neonatal Care centers of Complete Emergency (CEmONC) of the Collines department from 2018 to 2022. An estimate of the ratios of maternal deaths occurring at the level of the EmONC centers of the Collines department from 2018-2022 was carried out followed by constructive suggestions. Results: During the five years (2018 to 2022), the Collines department recorded 42,582 live births with 148 maternal deaths, i.e. a ratio of 348 maternal deaths per 100,000 live births. Between 2018 and 2022, the highest maternal death ratio was recorded in 2019, i.e. 425 maternal deaths per 100,000 live births for all EmONC centers and 607 maternal deaths per 100,000 live births in EmONC centers. The highest maternal death ratio at the BEmONC center level was recorded in 2020, i.e. 129 maternal deaths per 100,000 births. Conclusion: These results suggest that despite the implementation of EmONC in the Collines department, maternal deaths have not decreased. To improve these outcomes for a reduction in maternal deaths, urgent action must be taken.

Protocol of Investigation on Sudden Death at Autopsy, Including Molecular, Genetic and Toxicology Testing

The role of the autopsy: 1) Whether the death is ascribable to a natural or unnatural cause and when natural, if cardiac or extra-cardiac;2) The nosology of the cardiac diseases and the mechanism of cardiac death, whether arrhythmic or mechanical;3) If the cardiac disease is inherited, screening and counselling of the next of kin is required. About 30% of sudden deaths is ascribable to genetically determined morbid entities, mostly transmissible with the autosomal dominant pattern of inheritance, so that 50% of the first degree relatives are genetically affected (“carriers”) and exposed at risk;4) If toxic or illicit drug abuse was involved.

Challenging situation of coronary artery anomaly associated with ischemia and/or risk of sudden death

Coronary artery anomaly is known as one of the causes of angina pectoris and sudden death and is an important clinical entity that cannot be overlooked.The incidence of coronary artery anomalies is as low as 1%-2%of the general population,even when the various types are combined.Coronary anomalies are practically challenging when the left and right coronary ostium are not found around their normal positions during coronary angiography with a catheter.If there is atherosclerotic stenosis of the coronary artery with an anomaly and percutaneous coronary intervention(PCI)is required,the suitability of the guiding catheter at the entrance and the adequate back up force of the guiding catheter are issues.The level of PCI risk itself should also be considered on a caseby-case basis.In this case,emission computed tomography in the R-1 subtype single coronary artery proved that ischemia occurred in an area where the coronary artery was not visible to the naked eye.Meticulous follow-up would be crucial,because sudden death may occur in single coronary arteries.To prevent atherosclerosis with full efforts is also important,as the authors indicated admirably.