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Need for operational simplicity and timely disbursal of benefits—a qualitative exploration of the implementation of a direct benefit transfer scheme for persons with tuberculosis in India

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贫困所致传染病(英文) 2024年第3期13卷 1-15页

作者： Mohan Malu Thangaraj Jeromie W. V. Pandey Sumit Priya G. Sri Lakshmi Arunachalam Sivavallinathan Sharma Rahul Shewade Hemant Deepak Aishwarya B. Afeeq K. Khatoon Afsana Gokulvijay B. Sireesha Gude Chandra Kavita Nandhakumar S. Samuel Prince Viswanathan C. Nanditha Shanmugasundaram Devika Rao Raghuram Murhekar Manoj V. Jeyashree Kathiresan Indian Council of Medical Research-National Institute of Epidemiology R-127 TNHB Ayapakkam Chennai Tamil Nadu India TB Support Network WHO Country Office for India New Delhi India central tuberculosis division Government of India New Delhi India

Background Ni-kshay Poshan Yojana (NPY) is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB (PwTB). Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states, reported a 70% coverage and high median delay in benefit credit. We undertook a qualitative study between January and July 2023, to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY *** We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources. We conducted 36 in-depth interviews of national, district and field-level staff of the National tuberculosis Elimination Programme (NTEP) and NPY beneficiaries from 30 districts across nine states of India, selected using theoretical sampling. An analytical framework developed through inductive coding of a set of six interviews, guided the coding of the subsequent interviews. Categories and themes emerged through constant comparison and the data collection continued until theoretical *** Stakeholders perceived NPY as a beneficial initiative. Strong political commitment from the state administration, mainstreaming of NTEP work with the district public healthcare delivery system, availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation. However, the complex, multi-level benefit approval process, difficulties in accessing banking services, perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and *** The optimal utilization of NPY is enabled by strong political commitment and

关键词： National tuberculosis Elimination Programme Nutritional status Direct benefit transfer Ni-kshay Poshan Yojana Implementation Cash transfer scheme Grounded theory India

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The virulence regulator AbsR in avian pathogenic Escherichia coli has pleiotropic effects on bacterial physiology

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Journal of Integrative Agriculture 2024年第2期23卷 649-668页

作者： Dongfang Zhao Haobo Zhang Xinyang Zhang Fengwei Jiang Yijing Li Wentong Cai Ganwu Li State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150038China National Animal tuberculosis Reference Laboratory Division of Zoonoses SurveillanceChina Animal Health and Epidemiology CenterQingdao 266032China Department of Veterinary Diagnostic and Production Animal Medicine College of Veterinary MedicineIowa State UniversityAmesIowa 50011-1134the United States

Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic ***(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and ***(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for ***,a deep understanding of the AbsR regulatory mechanism as well as its regulon is *** this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)*** found that AbsR directly regulates 99 genes and indirectly regulates 667 ***,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC ***,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC ***,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule ***,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application.

关键词： avian pathogenic Escherichia coli(APEC) extraintestinal pathogenic Escherichia coli(ExPEC) AbsR RNA-Seq ChIP-Seq gene regulation

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Design,synthesis,and biological evaluation of 1,2,4-triazole derivatives as potent antitubercular agents

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Chinese Chemical Letters 2024年第3期35卷 326-331页

作者： Yu Wen Shichun Lun Yuxue Jiao Wei Zhang Tianyu Hu Ting Liu Fan Yang Jie Tang Bing Zhang William R.Bishai Li-Fang Yu Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China Center for tuberculosis Research Department of MedicineDivision of Infectious DiseaseJohns Hopkins School of MedicineBaltimoreMD21231-1044United States Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Shanghai Key Laboratory of Green Chemistry and Chemical Process School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China

Inhibition of mycobacterial membrane protein large 3(MmpL3)thereby affecting the mycolic acid biosynthetic pathway has been proven to be an effective strategy for developing antitubercular *** on the X-ray crystal structure of MmpL3 inhibitor complexes,a series of novel 1,2,4-triazole derivatives were designed,synthesized and evaluated antitubercular activity against Mtb strain *** structure–activity relationship exploration resulted in the identification of compounds 21 and 28,which possess potent antitubercular activity against Mtb strain H37Rv[minimum inhibitory concentration(MIC)=0.03–0.13μg/mL]and the clinical isolates of multidrug resistance(MDR)and extensive drug resistance(XDR)tuberculosis(MIC=0.06–1.0μg/mL).Moreover,compounds 21 and 28 showed neglectable cytotoxicity(IC_(50)≥32μg/mL)to the mammalian Vero cells and favorable physicochemical and pharmacokinetic properties according to the in silico absorption,distribution,metabolism and excretion(ADME)***,the potential target of representative 1,2,4-triazole 28 was identified to be MmpL3 using a microscale thermophoresis(MST)assay.

关键词： tuberculosis MDR and XDR-TB MmpL3 inhibitor 1 2 4-Triazole Structure-based drug design

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Evaluation of IFIT3 and ORM1 as Biomarkers for Discriminating Active tuberculosis from Latent Infection

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Current Medical Science 2022年第6期42卷 1201-1212页

作者： Bing-fen YANG Fei ZHAI Shan YU Hong-juan AN Zhi-hong CAO Yan-hua LIU Ruo WANG Xiao-xing CHENG tuberculosis Prevention and Control Key Laboratory Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and TreatmentInstitute of Senior Department of Tuberculosisthe Eighth Medical Center of Chinese PLA General HospitalBeijing100091China Fourth division Senior Department of Tuberculosisthe Eighth Medical Center of PLA General HospitalBeijing100091China Department of tuberculosis Prevention and Control Senior Department of Tuberculosisthe Eighth Medical Center of PLA General HospitalBeijing100091China

Objective Current commercially available immunological tests cannot be used for discriminating active tuberculosis(TB)from latent TB *** evaluate the value of biomarker candidates in the diagnosis of active TB,this study aimed to identify differentially expressed genes in peripheral blood mononuclear cells(PBMCs)between patients with active TB and individuals with latent TB infection by transcriptome *** The differentially expressed genes in unstimulated PBMCs and in Mycobacterium tuberculosis(Mtb)antigen-stimulated PBMCs from patients with active TB and individuals with latent TB infection were identified by transcriptome *** candidate genes were evaluated in cohorts consisting of 110 patients with TB,30 individuals with latent TB infections,and 50 healthy controls by quantitative real-time *** operating characteristic(ROC)curve analysis was performed to calculate the diagnostic value of the biomarker *** Among the differentially expressed genes in PBMCs without Mtb antigen stimulation,interferon-induced protein with tetratricopeptide repeats 3(IFIT3)had the highest area under curve(AUC)value(0.918,95%CI:0.852-0.984,P<0.0001)in discriminating patients with active TB from individuals with latent TB infection,with a sensitivity of 91.86%and a specificity of 84.00%.In Mtb antigen-stimulated PBMCs,orosomucoid 1(ORM1)had a high AUC value(0.833,95%CI:0.752-0.915,P<0.0001),with a sensitivity of 81.94%and a specificity of 70.00%.Conclusion IFIT3 and ORM1 might be potential biomarkers for discriminating active TB from latent TB infection.

关键词： tuberculosis biomarker latent tuberculosis infection interferon-induced protein with tetratricopeptide repeats 3 orosomucoid 1

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Spatial-temporal Analysis of tuberculosis at the Community Level in the Baoshan District, Shanghai 2014–2019

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Biomedical and Environmental Sciences 2022年第5期35卷 458-462页

作者： MA Zhi Tao WANG Na HE Fan LIU Xiao Feng SHEN Xin Department of tuberculosis and HIV/AIDS Prevention Baoshan Centers for Disease Control and PreventionBaoshan 201901ShanghaiChina division of tuberculosis and HIV/AIDS Prevention Shanghai Municipal Center for Disease Control and PreventionShanghai 200336China Shanghai Institutes of Preventive Medicine Shanghai 200336China

Mycobacterium tuberculosis is the primary bacteria that leads to human tuberculosis(TB),which usually affects the pulmonary *** is one of the top 10 causes of death worldwide;however,China is one of eight countries th... 详细信息

关键词： organs tuberculosis death

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tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges

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World Journal of Diabetes 2024年第5期15卷 853-866页

作者： Md Abdul Alim Al-Bari Nicholas Peake Nabil Eid Department of Pharmacy University of RajshahiRajshahi 6205Bangladesh Biosciences and Chemistry and Biomolecular Research Centre Sheffield Hallam UniversitySheffield S11WBUnited Kingdom Department of Anatomy Division of Human BiologySchool of MedicineInternational Medical UniversityKuala Lumpur 57000Malaysia

tuberculosis(TB)remains a leading cause of death among infectious diseases,particularly in poor *** infections,multidrug-resistant and ex-tensively drug-resistant TB strains,as well as the coexistence of chronic illnesses such as diabetes mellitus(DM)greatly aggravate TB morbidity and ***[particularly type 2 DM(T2DM)]and TB have converged making their control even more *** contemporary global epidemics,TB-DM behaves like a syndemic,a synergistic confluence of two highly prevalent diseases.T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive *** a bidirectional relationship exists between TB and DM,it is necessary to concurrently treat both,and promote recommendations for the joint management of both *** are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure,and *** addition,autophagy may play a role in these ***,the TB-DM comorbidities present several health challenges,requiring a focus on multidisciplinary collaboration and integrated strategies,to effectively deal with this double *** effectively manage the comorbidity,further screening in affected countries,more suitable drugs,and better treatment strategies are required.

关键词： Diabetes mellitus tuberculosis Coinfections Comorbidity Drug-drug interactions Autophagy Treatment challenges

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Mycobacterium tuberculosis latency-associated antigen Rv1733c SLP improves the accuracy of differential diagnosis of active tuberculosis and latent tuberculosis infection

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Chinese Medical Journal 2022年第1期135卷 63-69页

作者： Lifan Zhang Huimin Ma Shijun Wan Yueqiu Zhang Mengqiu Gao Xiaoqing Liu division of Infectious Diseases Department of Internal MedicineState Key Laboratory of Complex Severe and Rare DiseasePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Clinical Epidemiology Unit Peking Union Medical CollegeInternational Clinical Epidemiology NetworkBeijing 100730China Center for tuberculosis Research Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of tuberculosis Beijing Chest HospitalCapital Medical University/Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China

Background: Differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) has been a challenge for clinicians in high TB burden countries. The purpose of this study was to improve the accuracy of differential diagnosis of ATB and LTBI by using fluorescent immunospot (FluoroSpot) assay to detect specific Th1 cell immune responses. The novelmycobacterium tuberculosis (MTB) latency-associated antigens Rv1733c and synthetic long peptides derived from Rv1733c (Rv1733c SLP) were used based on virulence factors early secreting antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10).Methods: Fifty-seven ATB cases, including 20 pathogen-confirmed ATB and 37 clinically diagnosed ATB, and 36 LTBI cases, were enrolled between January and December 2017. FluoroSpot assay was used to detect the interferon γ (IFN-γ) and interleukin 2 (IL-2) secreted by the specific T cells after being stimulated with MTB virulence factors ESAT-6 and CFP-10, MTB latency-associated antigens Rv1733c and Rv1733c SLP. The receiver operating characteristic (ROC) curve was used to define the best cutoff value of latency-associated antigens in the use of differentiating ATB and LTBI. The sensitivity, specificity, predictive value, and likelihood ratio of ESAT-6 and CFP-10-FluoroSpot combined with latency-associated antigen in the differential diagnosis of ATB and LTBI were also ***: Following the stimulation with Rv1733c and Rv1733c SLP, the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP had the largest area under the ROC curve, which was 0.766. With a cutoff value of 1 (spot-forming cells [SFCs]/2.5 × 105 peripheral blood mononuclear cells) for frequency, the sensitivity and specificity of distinguishing ATB from LTBI were 72.2% and 73.7%, respectively. ESAT-6 and CFP-10-FluoroSpot detected the frequency and proportion of single IFN-γ-secreting T cells;the sensitivity and specificity of distinguishing ATB from LTBI were 82.5% a

关键词： Mycobacterium tuberculosis latency-associated antigens Active tuberculosis Latent tuberculosis infection Differential diagnosis

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Stearoyl-CoA desaturase 1: A potential target for non-alcoholic fatty liver disease?-perspective on emerging experimental evidence

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World Journal of Hepatology 2022年第1期14卷 168-179页

作者： Shanmugam Murugaiha Jeyakumar Ayyalasomayajula Vajreswari division of Lipid Biochemistry National Institute of NutritionHyderabad 500007TelanganaIndia Department of Clinical Pharmacology National Institute for Research in TuberculosisChennai 600031Tamil NaduIndia

Non-alcoholic fatty liver disease(NAFLD)is a progressive disease and one of the leading causes of *** unnamed disease has become a global epidemic disease of public health *** spectrum of diseases manifests itself with initial accumulation of excessive triglycerides(due to de novo lipogenesis)in the hepatocytes,leading to simple *** its aetiology is multi-factorial,lifestyle changes(diet and physical activity)are considered to be the key thriving *** this context,high fructose consumption is associated with an increased risk for developing NAFLD in humans,while high-fructose feeding to experimental animals results in hepatic steatosis and non-alcoholic steatohepatitis,by increasing hepatic *** several lipogenic genes,the endoplasmic reticulum-bound stearoyl-CoA desaturase 1(SCD1)is the key determinant of triglycerides biosynthesis pathway,by providing monounsaturated fatty acids,through the incorporation of a double bond at the delta-9 position of saturated fatty acids,specifically,palmitic(C16:0)and stearic(C18:0)acids,yielding palmitoleic(C16:1)and oleic(C18:1)acids,*** experimental studies involving SCD1 gene knockout and diet-induced rodent models have demonstrated that SCD1 plays a key role in the development of NAFLD,by modulating hepatic lipogenesis and thus triglyceride accumulation in the *** pharmacological and dietary intervention studies have shown the benefits of inhibiting hepatic SCD1 in the pathogenesis of *** this review,we give an overview of SCD1 in NAFLD,based on the current experimental evidence and the translational applicability of SCD1 inhibition in human NAFLD conditions,besides discussing the limitations and way-forward.

关键词： Steatosis Lipids Fatty acids Vitamin A Metabolic syndrome Obesity

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Treatment outcomes and adverse drug reactions among patients with drug-resistant tuberculosis receiving all-oral,long-term regimens:First record viewing report from Pakistan

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Asian Pacific Journal of Tropical Medicine 2023年第2期16卷 58-64,I0003页

作者： Hira Aslam Asad Omar Razia Fatima Usman Rasool Aashifa Yaqoob Waseem Ullah Aamir Khan Yusra Habib Khan Tauqeer Hussain Mallhi Provincial tuberculosis Control Program Punjab Pakistan Cardio-metabolic division CCL Research Laboratories Lahore PunjabPakistan Common Management Unit National Tuberculosis Control Program of PakistanIslamabadPakistan Department of Pharmacy Practice Shifa College of Pharmaceutical SciencesShifa Tameer-e-Millat UniversityIslamabadPakistan Association for Social Development IslamabadPakistan Department of Clinical Pharmacy College of PharmacyJouf UniversitySakakaAl-Jouf ProvinceSaudi Arabia

Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant ***:This retrospective study was conducted at 10 Programmatic Management of Drug Resistant tuberculosis sites in Punjab province of *** receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e.6th month culture conversion or final outcomes(cured,complete,lost to follow-up,failure,death)available,were included in the *** was extracted from electronic data management *** the reporting and management of adverse drug events,active tuberculosis drug safety monitoring and management was implemented across all *** the data was analyzed using SPSS version ***:Out of 947 drug resistant tuberculosis patients included in this study,579(68%)of the patients had final outcomes *** these,384(67.9%)successfully completed their *** of 368(32%)patients who had their interim results available,all had their 6th month culture *** new medications was thought to result in serious adverse outcomes such as QT ***,this study did not record any severe adverse events among ***:All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.

关键词： All-oral long-term regimens Long-term regimens Bedaquiline Linezolid Clofazimine Drug resistant tuberculosis Treatment outcomes aDSM

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Genomic medicine in clinical practice:national genomic medicine program in Japan

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Cancer Biology & Medicine 2024年第1期21卷 4-9页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~*** statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in *** surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has *** 38,000 people died of cancer in *** National Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： Cancer cancer death

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