Key Factors to Consider When Introducing a New Vaccine in Low-Income Settings: Lessons from Malawi Expanded Program on Immunization

Introduction: As new vaccines become available, countries must assess the relevance to introduce them into their vaccination schedules. Malawi has recently introduced several new vaccines and plans to introduce more. This study was conducted to identify key factors that need to be considered when deciding to introduce a new vaccine and current challenges faced by low and middle income countries using Malawi as an example. Methodology: The study employed a desk review approach, examining published literature from various sources such as PubMed, Medline, and Google Scholar. Policy documents from organizations like the World Health Organization, GAVI the Alliance, and the Ministry of Health for Malawi were also included. A total of 99 articles and documents on new vaccine introduction, challenges of immunization, policy documents in immunization and health systems strengthening were included. The review focused on addressing five key areas critical to new vaccine introduction namely: the need for a vaccine, availability of the vaccine, safety and effectiveness of the vaccine, demand for the vaccine, and the prudent use of public or private funds. Results: Malawi considered the burden of cervical cancer and the significance of malaria in the country when introducing the HPV and malaria vaccines. The country opted for vaccines that can be handled by the cold chain capacity and available human resources. Despite that malaria vaccine and Typhoid Conjugate Vaccine trials were done in country, there are limited vaccine safety and efficacy trials conducted in Malawi, leading to a reliance on WHO-prequalified vaccines. Demand for newly introduced vaccines varied, with high demand for Oral Cholera Vaccine during a cholera outbreak, while demand for COVID-19 vaccines decreased over time. Although cost-effectiveness studies were limited in the country, 2 studies indicated that Typhoid Conjugate Vaccine and malaria vaccine would be cost effective. All these have been implemented despite having challenges like lack of accurate surveillance data, inadequate cold chain capacity, limited safety and efficacy vaccine clinical trials, political influence, and limited funding. Conclusion: Despite several challenges Malawi set a good example of the careful considerations required before introducing a new vaccine. The process involves data review, priority setting, precise planning, and consultation with stakeholders. Low-income countries should invest in vaccine safety, efficacy, and cost-effectiveness trials.

Analysis of Epidemiological Characteristics of Varicella Before and After the Implementation of the Two-dose Varicella Vaccine Immunization Program in Banan District of Chongqing City

Objective:To explore the changes in the epidemiological characteristics of varicella before and after implementing the two-dose varicella vaccine(VarV)immunization program in the Banan District of Chongqing and to provide a reference for future epidemic prevention and control.Methods:The data of reported varicella cases in Banan District from 2014 to 2023 were collected and analyzed using the China Disease Prevention and Control Information System.Descriptive epidemiological methods were employed to assess the changes in the reported incidence of varicella before(2014-2018)and after(2019-2023)the implementation of the two-dose VarV immunization program.Results:The average annual reported incidence rate of varicella in Banan District from 2014 to 2023 was 81.53 per 100,000.From 2014 to 2018,the reported incidence rate showed an upward trend year by year(trend x2=223.96,P<0.05).However,the reported incidence rate decreased from 2019 to 2023(trend x?=189.51,P<0.05).Before and after the adjustment of the immunization program,the reported incidence rate for the 5-9 years old group was 774.62 per 100,000 and 476.98 per 100,000,respectively,with a statistically significant difference(x2=161.26,P<0.05).The onset of varicella showed a bimodal distribution,with peak incidence periods in May-June and October-December.From 2014 to 2023,a total of 155,181 doses of VarV were administered in Banan District.The estimated annual vaccination rate for the first varicella vaccine(VarV1)from 2019 to 2023 was 86.28%,and for the second dose(VarV2)was 59.18%.The primary vaccination targets were the 5-9-year-old group,accounting for 64.21%.Conclusion:After implementing the two-dose VarV immunization program in Banan District,the vaccination rate increased yearly,and the reported incidence of varicella showed a downward trend.The incidence rate of varicella in children aged 5-9 years reduced significantly,but the overall downward trend for the entire population was not as pronounced.Therefore,it is necessary to increase the vaccination rate of VarV2.

Glia-to-neuron reprogramming to the rescue?

Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.

Neurocircuit regeneration by extracellular matrix reprogramming

The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECM regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(Miyata et al.,2012),cation buffering(Moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic remodeling of the brain's ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases.

Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

Evaluation of Comparative Management of Expanded Program Immunization for Children in Iran and in the World

Background: EPI is one of the most cost-effective public health interventions that have already been identified. Mass vaccination is one of the most effective public health strategies that lead to a dramatic reduction in the incidence of many infectious diseases. This is a descriptive study (eco-logical exploratory) where data about the status of routine immunization of children under 6 years in 6 selected countries in terms of the routine immunization programs in each country, the coverage and reported cases of vaccine-preventable diseases from 2006 to 2008 were collected assuming that each country is a representative of a Continent;data about the status of Iran were also collected and a comparative study was performed in the next step. It is worth mentioning that selecting these countries was according to health experts to consolidate the data. Collection tools are data of international (WHO and UNICEF) and national organizations of the above countries. In all countries surveyed, triple vaccine, vaccines of polio, hepatitis B, measles, rubella and mumps are part of the routine immunization program for children under the age of 6 years, with the explanation that in South Africa only measles vaccine is injected instead of measles, rubella and mumps vaccines. The coverage rate of the vaccine and other vaccines in Iran was the best compared to other countries. This represents the widespread activity of health care systems of the country in the field of vaccination and tireless efforts of healthcare workers and health centers.

A Comparison of National Immunization Programme Target Population Estimates with Data from an Independent Source and Differences in Computed Coverage Levels for the Third Dose of DTP Containing Vaccine

Background: Comparison of target populations for immunization used by national immunization programmes with independent sources can be useful for identifying irregular patterns. Similarly, understanding differences in computed coverage levels that result from changes in target population estimates can be important. Methods: Using data reported annually by national immunization programmes to WHO and UNICEF, we compared the national number of births and surviving infants with estimates reported by the United Nations Population Division (UNPD). We also re-computed and compared coverage levels for the third dose of DTP containing vaccine (DTP3) using the nationally reported number of children vaccinated with DTP3 (the numerator) and the nationally reported number of children in the target population (the denominator) and compared this value with DTP3 coverage computed using the nationally reported number of children vaccinated and the UNPD estimate of the national number of surviving infants as an independent denominator. Results: We observed differences in the number of births and surviving infants reported by national immunization programmes compared with those estimated by the UNPD. Year-to-year changes in the number of births and surviving infants reported by national immunization programmes often exceeded those estimated by the UNPD. The re-computed administrative coverage levels for DTP3 using a nationally reported target population tended to be higher on average than those re-computed using the UNPD target population estimates. Conclusion: Target population estimates are a challenge for immunization programmes, and comparison to independent sources can be useful. There is increasing need to trace and better understand the processes and conditions affecting the enumeration and recording of the number of children in the target population for immunization services and the number of children vaccinated while recognizing that the challenge to do so is greater in some locations than others.

Proportionate Target Population Estimates Used by National Immunization Programmes in Sub-Saharan Africa and Comparison with Values from an External Source

Background: In order to effectively plan the delivery of immunization services, manage stock and supply levels and target interventions, national immunization programmes (NIP) must have an estimate of the target population they serve. To overcome challenges with target population estimation, some NIPs apply “rule-of-thumb” conversion factors to total population estimates. We compare these proportionate target population values with those from an external source. Methods: Using data reported by national immunization programmes in sub-Saharan Africa, we computed the proportionate target population as the number of births, surviving infants and children under 5 years of age, respectively, as a proportion of the total population size. We compared these values with those estimates computed from United Nations Population Division (UNPD) data. We then recomputed NIP target population sizes using the proportionate target population values from the UNPD applied to the total population size reported by NIP. Results: Data were available from 47 sub-Saharan Africa countries. Births as a proportion of the total population were greater within reports from NIP (median, 0.0400;IQR: 0.350 - 0.0437) compared to values from UNPD estimates (median, 0.0364;IQR: 0.0332 - 0.0406). Similar patterns were observed for surviving infants (median: NIP, 0.0360;UNPD, 0.0337) and children under 5 years of age (median: NIP, 0.1735;UNPD, 0.1594). The percent difference in proportionate target population ratios between reports from NIPs and the UNPD was >10% in 23 countries for births, in 18 countries for surviving infants, in 15 countries for children under 5 years of age. After re-computing target populations using UNPD proportionate target population values applied to NIP reported total population, recomputed administrative coverage levels for the third dose of DTP containing vaccine were higher in 32 of the 47 countries compared to reported administrative coverage levels. Conclusion: Because childhood immunization-related target populations are among the more difficult ones to accurately estimate and project, immunization programmes in sub-Saharan Africa are encouraged to include a critical assessment of the target population values, in conjunction with their national statistics system, as part of the on-going programme monitoring process.

Outcomes of the Expanded Programme on Immunization Pre-Service Training Initiatives in Kenya: A Mixed Methods Study

Background: The Maternal and Child Survival Program of United States Agency for International Development conducted a study in 2017 to assess the outcome of an initiative to strengthen Expanded Programme on Immunization (EPI) pre-service training. The pre-service training initiative was undertaken by the Ministry of Health (MOH) with support from partners in 2012-2016. The overall objective of the study was to assess the adoption and effectiveness of the initiative in the competency (knowledge, skills and attitude) of graduate nurses. Methods: The study included a conveniently selected sample of 14 pre-service training institutions, 23 field practicum sites, and 29 health facilities in western Kenya, and used quantitative and qualitative methods of data collection. Results: All pre-service training institutions were found to have adapted the WHO EPI prototype curriculum. Overall, tutors followed training method in the classroom as suggested in the curriculum, except evaluation of students’ learning lacked tests or quizzes. Students had opportunities for hands-on practical experience in the field practicum sites. Graduate nurses were found to have acquired the skills for vaccinating children. However, some pre-service training institutions lacked functional skills labs for practical learning of students. In addition, students did not receive up-to-date information on EPI program, and lacked knowledge and skills on monitoring and documentation of EPI coverage during preservice training. Conclusions: It appears that the EPI pre-service training strengthening initiatives facilitated competency-based EPI training of nurses in Kenya. However, preservice training institutions still have scope for improvement in the skills lab, hand-washing practice, providing up-to-date information, and training students on coverage monitoring and documentation.

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.

Factors Associated with Antibody Levels among Children Aged 15 to 59 Months Vaccinated against Hepatitis B during the Expanded Program on Immunization in Cameroon

Background: the hepatitis B virus infection remains a major public health problem worldwide. It can lead to a liver cirrhosis and/or hepatocellular carcinoma. The World Health Organisation (WHO) has recommended the implementation of generalised vaccination programs against hepatitis B. In Cameroon, this vaccine was introduced in the expanded program on immunization (EPI) in 2005, but few studies have assessed the immune response. Objective: the general objective of this study was to identify factors associated with antibody levels among children aged from 15 to 59 months vaccinated against hepatitis B during the EPI in Cameroon. Method: this was a cross-sectional study carried out from December 2021 to June 2022 in a paediatric centre of Yaoundé (Cameroon). We analysed the antibody level in children vaccinated against hepatitis B within the framework of the EPI. We enrolled children who had received a series of 3 intramuscular doses of hepatitis B vaccine at 6, 10 and 14 weeks after birth. Some children could receive a 4th booster dose between 12 months. The antibody level was assessed by measuring the anti-HBs in such children, aged 15 - 59 months. A good immunization was defined as a serum level of anti-HBs antibody level above 100 IU/mL;a poor immunization, for an anti-HBs antibody level between 10 and 100 IU/mL;and a non-immunization, for an anti-HBs antibody level < 10 IU/mL. Association between explored factors and poor or non-immunization was evaluated through the Chi square test. The significance threshold was defined at p < 0.05. Results: sixty subjects were included in the study with a slight female majority: 31 cases (52%). The average age was 38.5 ± 15.7 months (range 15 - 59 months). We found 32 (53%) cases of good immunization;21 (35%) of poor immunization;and 7 children (12%) with a non-immunization. The only factor associated with poor or non-immunization was the age between 37 - 59 months (p = 0.016). Conclusion: Anti HBs Antibody levels in children vaccinated against hepatitis B virus were globally satisfactory in our series. Results show an association between low antibody levels with older age (over 36 months), suggesting a circulating antibodies levels decrease over time, yet deemed protecting until 59 months.

Uncertainty quantification of inverse analysis for geomaterials using probabilistic programming

Uncertainty is an essentially challenging for safe construction and long-term stability of geotechnical engineering.The inverse analysis is commonly utilized to determine the physico-mechanical parameters.However,conventional inverse analysis cannot deal with uncertainty in geotechnical and geological systems.In this study,a framework was developed to evaluate and quantify uncertainty in inverse analysis based on the reduced-order model(ROM)and probabilistic programming.The ROM was utilized to capture the mechanical and deformation properties of surrounding rock mass in geomechanical problems.Probabilistic programming was employed to evaluate uncertainty during construction in geotechnical engineering.A circular tunnel was then used to illustrate the proposed framework using analytical and numerical solution.The results show that the geomechanical parameters and associated uncertainty can be properly obtained and the proposed framework can capture the mechanical behaviors under uncertainty.Then,a slope case was employed to demonstrate the performance of the developed framework.The results prove that the proposed framework provides a scientific,feasible,and effective tool to characterize the properties and physical mechanism of geomaterials under uncertainty in geotechnical engineering problems.

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.

Recent Progress in Reinforcement Learning and Adaptive Dynamic Programming for Advanced Control Applications

Reinforcement learning(RL) has roots in dynamic programming and it is called adaptive/approximate dynamic programming(ADP) within the control community. This paper reviews recent developments in ADP along with RL and its applications to various advanced control fields. First, the background of the development of ADP is described, emphasizing the significance of regulation and tracking control problems. Some effective offline and online algorithms for ADP/adaptive critic control are displayed, where the main results towards discrete-time systems and continuous-time systems are surveyed, respectively.Then, the research progress on adaptive critic control based on the event-triggered framework and under uncertain environment is discussed, respectively, where event-based design, robust stabilization, and game design are reviewed. Moreover, the extensions of ADP for addressing control problems under complex environment attract enormous attention. The ADP architecture is revisited under the perspective of data-driven and RL frameworks,showing how they promote ADP formulation significantly.Finally, several typical control applications with respect to RL and ADP are summarized, particularly in the fields of wastewater treatment processes and power systems, followed by some general prospects for future research. Overall, the comprehensive survey on ADP and RL for advanced control applications has d emonstrated its remarkable potential within the artificial intelligence era. In addition, it also plays a vital role in promoting environmental protection and industrial intelligence.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Smart Healthcare Using Data-Driven Prediction of Immunization Defaulters in Expanded Program on Immunization (EPI)

Immunization is a noteworthy and proven tool for eliminating lifethreating infectious diseases,child mortality and morbidity.Expanded Program on Immunization(EPI)is a nation-wide program in Pakistan to implement immunization activities,however the coverage is quite low despite the accessibility of free vaccination.This study proposes a defaulter prediction model for accurate identification of defaulters.Our proposed framework classifies defaulters at five different stages:defaulter,partially high,partially medium,partially low,and unvaccinated to reinforce targeted interventions by accurately predicting children at high risk of defaulting from the immunization schedule.Different machine learning algorithms are applied on Pakistan Demographic and Health Survey(2017–18)dataset.Multilayer Perceptron yielded 98.5%accuracy for correctly identifying children who are likely to default from immunization series at different risk stages of being defaulter.In this paper,the proposed defaulters’prediction framework is a step forward towards a data-driven approach and provides a set of machine learning techniques to take advantage of predictive analytics.Hence,predictive analytics can reinforce immunization programs by expediting targeted action to reduce dropouts.Specially,the accurate predictions support targeted messages sent to at-risk parents’and caretakers’consumer devices(e.g.,smartphones)to maximize healthcare outcomes.

Impact of Hepatits B Vaccination as an Important Indicator for Immunization Program in Albania

Albania has been a country with a high prevalence of hepatitis B virus. Hepatitis B vaccine has been introduced nationwide in Albanian Immunization Program in 1994. Hepatitis B is given at birth, as a separate antigen, followed by three doses at 2, 4 and 6 months, where Hepatitis B, starting from 2009, is part of pentavalent vaccine of DTP-HepB-Hib. The aim of this study was to evaluate Immunization Program with Hepatitis B vaccination in order to prove program efficacy, increase public confidence in immunizations and advocate for sustainable immunization programs. Methodology was based on three components such as Immunization coverage surveys, serologic surveys and surveillance for acute cases of Hepatitis B. Results of this study showed that vaccination coverage is really high, more than 95% all over the country and with drop-out rates less than 10%. Anti-HBs levels in immunized children were very high in comparison with unimmunized ones. Incidence of HBV in children 0-14 years old is almost zero. Such results tell us that Hepatitis B vaccination is one of the most fruitful strategies for long term control of Hepatitis B disease.

Adaptive Optimal Discrete-Time Output-Feedback Using an Internal Model Principle and Adaptive Dynamic Programming

In order to address the output feedback issue for linear discrete-time systems, this work suggests a brand-new adaptive dynamic programming(ADP) technique based on the internal model principle(IMP). The proposed method, termed as IMP-ADP, does not require complete state feedback-merely the measurement of input and output data. More specifically, based on the IMP, the output control problem can first be converted into a stabilization problem. We then design an observer to reproduce the full state of the system by measuring the inputs and outputs. Moreover, this technique includes both a policy iteration algorithm and a value iteration algorithm to determine the optimal feedback gain without using a dynamic system model. It is important that with this concept one does not need to solve the regulator equation. Finally, this control method was tested on an inverter system of grid-connected LCLs to demonstrate that the proposed method provides the desired performance in terms of both tracking and disturbance rejection.

Cytokine release syndrome induced by anti-programmed death-1 treatment in a psoriasis patient:A dark side of immune checkpoint inhibitors

In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expressed in T cells that regulates the immune system’s activity to prevent over-activation and tissue damage caused by inflammation.However,PD-1 is also expressed in tumor cells and functions as an immune evasion mechanism,making it a therapeutic target to enhance the immune response and eliminate tumor cells.Consequently,immune checkpoint inhibitors(ICIs)have emerged as an option for certain tumor types.Nevertheless,blocking immune checkpoints can lead to immune-related adverse events(irAEs),such as psoriasis and cytokine release syndrome(CRS),as exemp-lified in the clinical case presented by Zhou et al involving a patient with adva-nced gastric cancer who received sintilimab,a monoclonal antibody targeting PD-1.Subsequently,the patient experienced exacerbation of psoriasis and CRS.The objective of this editorial article is to elucidate potential immunologic mechanisms that may contribute to the development of CRS and psoriasis in patients receiving ICIs.It is crucial to acknowledge that while ICIs offer superior safety and efficacy compared to conventional therapies,they can also manifest irAEs affecting the skin,gastrointestinal tract,or respiratory system.In severe cases,these irAEs can lead to life-threatening complications such as circulatory shock or multiorgan failure.Consequently,it is recommended that patients receiving ICIs undergo regular monitoring to identify and manage these adverse events effectively.

In vivo astrocyte reprogramming following spinal cord injury

Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site.The absence of spontaneous axonal regeneration after injury results from neuron-intrinsic and neuron-extrinsic parameters.Indeed,not only adult neurons display limited capability to regrow axons but also the injury environment contains inhibitors to axonal regeneration and a lack of growth-promoting factors.Amongst other cell populations that respond to the lesion,reactive astrocytes were first considered as only detrimental to spontaneous axonal regeneration.Indeed,astrocytes.