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Colorectal cancer screening:A review of current knowledge and progress in research

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World Journal of gastrointestinal Oncology 2024年第4期16卷 1119-1133页

作者： Sara Ramos Lopes Claudio Martins Inês Costa Santos Madalena Teixeira Élia.gamito Ana Luisa Alves Department of gastroenterology Centro Hospitalar de SetúbalSetúbal 2910-446Portugal

Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial diagnosis.Furthermore,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been increasing.Screening and early detection are pivotal to improve CRC-related outcomes.It is well established that CRC screening not only reduces incidence,but also decreases deaths from CRC.Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the literature.However,uncertainties persist regarding the optimal screening method,age intervals and periodicity.Moreover,adherence to CRC screening remains globally low.In recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these barriers.However,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice.In this review,we aim to cover the current evidence surrounding CRC screening.We will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.

关键词： Colorectal cancer Screening Review Oncology Artificial intelligence

Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines

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Journal of Integrative Medicine 2024年第4期22卷 503-514页

作者： Li-hua Zhu Yu-pei lia.g lian Yang Feng Zhu Li-jun Jia He-gen lia Department of Oncology Longhua Hospital Shanghai University of Traditional Chinese Medicine Cancer Institute of Traditional Chinese Medicine Longhua Hospital Shanghai University of Traditional Chinese Medicine Department of Laboratory Medicine Huadong Hospital Fudan University

Objective:Studies have demonstrated that cycloastragenol induces antitumor effects in prostate, colorectal and gastric cancers; however, its efficacy for inhibiting the proliferation of lung cancer cells is largely unexplored. This study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer(NSCLC) and elucidates the underlying molecular mechanisms.Methods:The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation assays.Cycloastragenol-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide kit. To elucidate the role of cycloastragenol in the induction of apoptosis, apoptosis-related proteins were examined using Western blots.Immunofluorescence and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer cells. genetic techniques, including small interfering RNA technology,were used to investigate the underlying mechanisms. The effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor model.Results:Cycloastragenol triggered both autophagy and apoptosis. Specifically, cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1(NOXA), a critical apoptosis-related protein. Moreover, cycloastragenol induced a protective autophagy response through modulation of the adenosine 5?-monophosphate-activated protein kinase (AMPK)/unc-51-like autophagy-activating kinase (ULK1)/mammalian target of rapamycin (mTOR) pathway.Conclusion:Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in NSCLC. This insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to combating lung cancer.

关键词： Non-small cell lung cancer Cycloastragenol Autophagy Apoptosis

Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

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World Journal of gastrointestinal Oncology 2024年第1期16卷 234-243页

作者： João gramaça Isabel gomes Fernandes Carolina Trabulo Joana gonçalves Rita gameiro dos Santos Adriano Baptista Idília Pina Centro Hospitalar Barreiro Montijo Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal Medical Oncology Unit Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal

BACKgROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EgFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EgFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EgFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EgFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EgFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

关键词： Metastatic colorectal cancer Rat sarcoma virus mutational status Liquid biopsy Rat sarcoma virus wild-type Neo-rat sarcoma virus wild-type Anti-epidermal growth factor receptor therapy Case report

Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

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Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang Loujin Slitin Jakob Neef Shashank S.Chepurwar Regina Célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose Kathrin Kusch Carolin Wichmann Nicola Strenzke Barbara Vona Julia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany Collaborative Research Center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany göttingen graduate Center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory genomics group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing genomics group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHCs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary Materials.Otoferlin is distributed broadly within IHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

Assessment of the Indirect Cost of Drug Resistant Tuberculosis Treatment to Patients in a High Burden, Low Income Setting in Mozambique

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Journal of Tuberculosis Research 2024年第2期12卷 91-104页

作者： Júlia Malache António Domingas Pacala Isabelle Munyangaju Isaías Benzana Claudia Mutaquiha Dulce Osório Benedita José Edy Nacarapa Pereira Zindoga Faculdade de Cincias de Sade Universidade Catlica de Moambique Beira Moambique Programa Nacional de Controlo da Tuberculose Ministrio da Sade de Moambique Maputo Moambique ISglobal Hospital Clnic Universitat de Barcelona Barcelona Spain Tinpswalo Association Vincentian Association to Fight AIDS and TB Chokwe Mozambique Centro de Estudos e Apoio Psicolgico (CEAP) Universidade Eduardo Mondlane Maputo Moambique

Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from January 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psychosocial support, can significantly reduce the

关键词： Economic Costs Drug Resistance Tuberculosis Catastrophic Costs

An Analysis of the Accounting Costs Associated with 20-Month DR TB Regimens in Maputo City, Mozambique

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Journal of Tuberculosis Research 2024年第2期12卷 73-90页

作者： Júlia Malache António Isaías Benzana Isabelle Munyangaju Benedita José Dulce Osório Edy Nacarapa Claudia Mutaquiha Simeão Nhabinde Pereira Zindoga Universidade Catlica de Moambique Beira Moambique Centro de Estudos e Apoio Psicolgico (CEAP) Universidade Eduardo Mondlane Maputo Moambique ISglobal Hospital Clnic Universitat de Barcelona Barcelona Spain Tinpswalo Association Vincentian Association to Fight AIDS and TB Chokwe Mozambique Programa Nacional de Controlo da Tuberculose Ministrio da Sade de Moambique Maputo Mozambique Faculdade de Economia Universidade Eduardo Mondlane Maputo Moambique

Introduction: Socioeconomic and demographic conditions in a country can influence tuberculosis incidence and mortality, with nearly 95% of tuberculosis-related deaths occurring in poorer countries. Mozambique is among the 30 countries with the highest TB burden. Objective: The study aimed to estimate the average direct medical cost of treating drug-resistant tuberculosis in 19 health centers in Maputo City, Mozambique. Methods: A retrospective analysis of direct medical costs was conducted on patients aged 18 and older who completed 20-month drug-resistant tuberculosis treatment regimens in Maputo City in 2019. Results: This analysis covered 140 patients who completed a 20-month treatment regimen, with 64.3% (78) being male and 35.7% (62) female. Approximately 50% of the participants were aged between 29 and 47. The average direct medical cost of DRTB treatment was $4789.43, reaching up to $6568.00, with a standard deviation of $753.26, including clinical interventions and treatment. Conclusion: The direct medical costs for a basic treatment package for a patient with drug-resistant TB in Mozambique equal 36 minimum wages. Developing alternative and innovative funding mechanisms and identifying ways to mitigate costs through the use of generic medicines would be beneficial.

关键词： Antitubercular Agents Multidrug-Resistant Healthcare Costs Tuberculosis Mozambique

Risk Stratification in Obstetrics: An Integrated Approach to Maternal Health

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Open Journal of Obstetrics and gynecology 2024年第6期14卷 903-910页

作者： Taina Crespo Mendonca Bianca Beatriz Soares dos Reis Júlia Cruz Coelho Antônio de Oliveira Battistini Pestana Vitória Carolina Barreto Negri Alvaro Augusto Trigo Department of Medicine University of Franca Franca Brazil

Introduction: Prenatal care is crucial for maternal and fetal health, highlighting the importance of obstetric risk stratification. This enables personalized care, avoiding unnecessary interventions and reducing costs. Conditions such as first trimester bleeding, spontaneous abortion, gestational trophoblastic disease, and ectopic pregnancy require specific approaches. Early identification of these complications is vital, especially in urgent and emergency obstetric cases, which demand immediate hospital attention. Objective: Comprehensive review of first trimester pathologies and gestational hypertension, focusing on obstetric risks and personalized prenatal management. Methods: Literature review on bleeding and gestational hypertension. Results: The study provides a detailed analysis of pathologies associated with first trimester uterine bleeding and hypertensive disorders, focusing on obstetric risk stratification. The main causes of maternal and fetal mortality are hypertensive disorders, hemorrhages, infections, childbirth complications, and abortion. Spontaneous abortion is common, with different classifications, ranging from threatened to missed abortion. Infected abortion is a severe complication. Brazil has restrictive abortion laws, but many unsafe abortions occur, resulting in high public health costs. Pharmacological treatment with misoprostol is a safe option. Other pathologies include gestational trophoblastic disease, ectopic pregnancy, and placenta previa. Preeclampsia and eclampsia are severe conditions requiring immediate treatment to avoid complications. Conclusion: Early identification and management of obstetric risk factors, such as uterine bleeding, are essential for positive maternal and fetal outcomes. A multidisciplinary approach is fundamental.

关键词： Obstetrics Emergencies Hypertension Pregnancy-Induced Uterine Hemorrhage Pregnancy Trimester First

Prevalence of Latent Tuberculosis Infection [LTBI] in Prison Officers: A Systematic Review and Meta-Analysis

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Open Journal of Respiratory Diseases 2024年第1期14卷 12-24页

作者： Thiago Poss Moreira gustavo Henrique Baraca Sanvezzo Maico Trevisol Renan William Mesquita Luiza Scalcon de Oliveira lia Beatriz Henke de Azevedo Cleide Viviane Buzanello Martins Lirane Elize Defante Ferreto Health Sciences Center Faculty of Medicine Western Paraná State University Francisco Beltr&#227o Brazil Health Sciences Center Postgraduate Program in Applied Health Sciences Western Paraná State University Francisco Beltr&#227o Brazil

This study aimed to perform a systematic review and meta-analysis to determine the LTBI prevalence in prison officers worldwide. A systematic search was performed in PubMed, WoS, Embase, and BVS, including all articles related to LTBI prevalence and risk factors. After critical evaluation and qualitative synthesis of the identified articles, a meta-analysis was used. Five studies carried out between 2012 and 2022 were included, with a total sample size of 1718 prison officers. The overall LTBI prevalence was 50% [95% confidence interval [CI]: 48% - 52%;n = 816], with high heterogeneity between studies. Smoking [OR = 1.76;CI 95% = 1.26 - 2.46] and males [OR = 2.08;CI 95% = 1.31 - 3.31] were positively related to a higher LTBI prevalence among prison officers. Thus, preventive measures and the rapid and accurate diagnosis of new cases should be emphasized to ensure tuberculosis control, especially among risk groups such as prison officers.

关键词： Latent Tuberculosis Mycobacterium tuberculosis Meta-Analysis Prevalence Occupational Exposure

Sexual Assault and Its Psychopathological Repercussions in the Life of Female Students in Northeastern Benin (2023)

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Open Journal of Psychiatry 2024年第3期14卷 163-178页

作者： Ireti Nethania Elie Ataigba Djibrilla Moussa Oumou Ousseyni Zika Fidélia Dotou Coovi Ignace Tokpanoude Anselme Djidonou Djibo Douma Maiga Francis Tognon Tchegnonsi Prosper gandaho Josiane Ezin Houngbe Faculté de Médecine & Institut de Formation en Soins Infirmiers et Obstétricaux Université de Parakou Parakou Bénin Service de Psychiatrie Départemental du Borgou Alibori Centre Hospitalier Universitaire Parakou Bénin Organisation Non gouvernementale de Soutien de Réhabilitation d’Insertion et de Réinsertion (SouRIR ONG) Parakou Bénin Faculté des Sciences de la Santé Université André Salifou de Zinder Zinder Niger Service de Psychiatrie H?pital National de Zinder Zinder Niger Faculté des Sciences de la Santé Université Abdou Moumouni de Niamey Niamey Niger Service de Psychiatrie H?pital National de Niamey Niamey Niger Faculté des Sciences de la Santé de Cotonou Université d’Abomey-Calavi Abomey-Calavi Bénin Service de Psychiatrie Centre National Hospitalier Universitaire - Hubert Koutoucou Maga de Cotonou Cotonou Bénin

Objective: The aim of the present study was to investigate the psychic repercussions of sexual assault among female students in Parakou in 2023. Methods: Descriptive cross-sectional study conducted from December 2022 to July 2023 among all students at the University of Parakou. The sampling technique was stratified non-proportional at two levels. The dependent variable was self-reported sexual assault. The psychopathological repercussions linked to sexual assault and explored in these students were: post-traumatic stress disorder assessed with the Post Traumatic Stress Disorder Checklist-5 (PCL-5) scale;and current depression screened with the Patient Health Questionnaire-9 (PHQ-9) scale. Results: A total of 376 female students from the University of Parakou meeting the inclusion criteria were surveyed. The average age of the subjects surveyed was 20.56 ± 2.46 years, with extremes of 16 and 32 years. A predominance of subjects under 25 was observed. The prevalence of sexual assault among female students at the University of Parakou was 10.63%. The types of aggression suffered were mostly rape (18 people;45%) and sexual touching (16 people;40%), and the aggressors were mainly friends/boyfriends (13;32.5%), family members (12;30.0%) and people from the house/neighborhood (9;22.5%). Psychological repercussions included depression in 72.5% (29) of cases, with mild depression in 30% (12), moderate depression in 37.5% (15) and severe depression in 5% (2). Anxiety disorders were present in 27.50% (11) of victims. The risk factors associated with sexual assault in these students were gravidity (p = 0.014;OR = 15.32), unhappy life events (p = 0.01;OR = 17.24), and age of first sexual intercourse (p = 0.016;OR = 4.608). Conclusion: One in ten female students in Parakou has been sexually assaulted. Once again, preventive action through effective sex education is a means of fighting the problem that should be prioritized for every girl and boy from an early age. Psychological support by specialists should be offered to any v

关键词： Sexual Assault Psychopathological Repercussions Benin 2023