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Structure-tissue exposure/selectivity relationship(STR) correlates with clinical efficacy/safety

Acta Pharmaceutica Sinica B 2022年第5期12卷 2462-2478页

作者： Wei Gao Hongxiang Hu Lipeng Dai Miao He Hebao Yuan Huixia Zhang Jinhui Liao Bo Wen Yan Li Maria Palmisano mohamed Dit Mady traore Simon Zhou Duxin Sun Department of Pharmaceutical Sciences College of PharmacyUniversity of MichiganAnn ArborMI 48109USA Translational Development and Clinical Pharmacology Bristol Myers SquibbSummitNJ 07920USA

Drug optimization, which improves drug potency/specificity by structure-activity relationship(SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However,the current drug optimization may overlook the structure-tissue exposure/selectivity-relationship(STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators(SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug’s plasma exposure was not correlated with drug’s exposures in the target tissues(tumor, fat pad, bone, uterus),while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug’s plasma exposure but altered drug’s tissue exposure/*** SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug’s tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.

关键词： Structure-activity-relationship(SAR) Structure-tissue exposure/selectivity relationship(STR) Drug optimization Clinical efficacy/toxicity Drug development

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血吸虫性膀胱炎的CT表现

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中华放射学杂志 2014年第2期48卷 132-134页

作者：王宇军胡利荣程有根茅国群杨光钊 Modya Camara mohamed traore 浙江省立同德医院放射科杭州310012 马里共和国巴马科市马里医院影像科

目的探讨血吸虫性膀胱炎的CT表现.方法回顾性分析32例经尿液细胞学检查找到虫卵证实的32例血吸虫性膀胱炎患者资料,所有患者均行CT平扫加增强扫描,观察病变累及部位和膀胱壁、输尿管等表现,并观察膀胱充盈及排空后的大小变化.结果 32... 详细信息

目的探讨血吸虫性膀胱炎的CT表现.方法回顾性分析32例经尿液细胞学检查找到虫卵证实的32例血吸虫性膀胱炎患者资料,所有患者均行CT平扫加增强扫描,观察病变累及部位和膀胱壁、输尿管等表现,并观察膀胱充盈及排空后的大小变化.结果 32例CT上均见膀胱壁蛋壳样或弧形钙化,增强后膀胱壁未钙化区轻度强化.除5例合并膀胱癌外,其余患者膀胱充盈及排空后大小变化基本正常.25例伴输尿管下段钙化,22例伴输尿管肾盂积水.11例男性患者中有4例可见精囊钙化.女性患者的子宫、卵巢和男性患者的前列腺均未见钙化.5例合并膀胱癌,膀胱壁明显不规则增厚,增强后中度强化.结论膀胱钙化是血吸虫性膀胱炎最典型的CT表现,有助于该病的诊断.

关键词：血吸虫病膀胱炎体层摄影术,X线计算机

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Management of Urological Emergencies at the Nianankoro Fomba Hospital in Segou: A Case Report of 72 Patients

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Open Journal of Urology 2022年第5期12卷 242-247页

作者： Sory I. Kone mohamed traore Ibrahim Yattara Tièmoko traore Karifala Haidara Frank M. Omam Mamadou T. Coulibaly Honoré J. G. Berthe Mamadou L. Diakite Urology Department Nianankoro Fomba Hospital Ségou Mali Liberal Bamako Mali Department of Urology CHU Gabriel TOURE Bamako Mali Department of Urology CHU du point G Bamako Mali

PURPOSE: Our aim was to present the diagnostic and therapeutic aspects of urological emergencies in a regional hospital. MATERIAL AND METHODS: We conducted a prospective study over a period of 6 months (April 2021 to September 2021) collecting all the emergencies received by the on-call urology team at the Nianankoro Fomba Hospital in Segou. This team was led by a DES in urology under the supervision of a urological surgeon. We were interested in age, sex of patients, diagnosis, number of patients hospitalised and type of surgery performed in emergency. RESULTS: We registered 72 patients. The mean age of our patients was 58.8 years with extremes of 6 and 90 years. Acute bladder retention was represented in 61% and total haematuria in 24%. Renal colic was reported in 8%. Acute prostatitis was reported in 4% of cases, and acute pyelonephritis in 1%. Urogenital trauma accounted for 6%. CONCLUSION: Although underestimated, in our context, the management of urological emergencies remains a regular activity of the urology department in view of the number of patients managed. Bladder drainage remains the most frequent procedure.

关键词： Urological Emergency Nianankoro Fomba Hospital Diagnosis Treatment

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MRI Contribution in the Diagnosis of Non-Traumatic Medular Compressions at the Mali Hospital of about 179 Cases

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Open Journal of Medical Imaging 2020年第4期10卷 186-195页

作者： Mody Abdoulaye Camara Mamadou N’Diaye Mamadou Bakary Coulibaly mohamed Maba traore Hawa Diarra Boubacar Mama Toure Abourahman Abdillahi Nour Salia Coulibaly Ilias Guindo Madani Ouologuem Sounkalo traore Mahamane Mariko Aphou Sallé Kone Moussa Konate Siaka Sidibe Medical Imaging Department of Mali Hospital Bamako Mali Radiology Unit of the Bamako Infirmary Hospital Bamako Mali Gynecology Department of Mali Hospital Bamako Mali Medical Imaging Department at Kati University Hospital Bamako Mali Neurology Unit of the Bamako Infirmary Hospital Bamako Mali Radiology Unit of the Reference Health Center of the Commune V Bamako Mali Medical Imaging Department of CHME Luxembourg Bamako Mali Radiotherapy Department of Mali Hospital Bamako Mali Radiology Department of CHU POINT G Bamako Mali

Slow spinal compressions are due to the development of an expansive process in the spinal canal. It is a very common pathology, the diagnosis of which is mainly clinical. However, magnetic resonance imaging occupies an essential place in the site diagnosis and etiological research in the management. Non-traumatic spinal cord compression is a diagnostic and therapeutic emergency, requiring early and appropriate management. MRI is the benchmark imaging examination for this pathology. No similar previous MRI study in Mali. We undertook this work with the aim to determine the place of MRI in the diagnosis of spinal cord compressions in Mali hospital. Method and Patients: This was a descriptive retrospective study, carried out at the hospital’s medical imaging department from January 1, 2017 to December 31, 2018 (02 years). It involved all patients, regardless of sex and age, sent for an MRI examination of the spine, and in whom spinal cord compression was diagnosed. We used a 0.35T low-field MRI machine with solid-state antennas. Results: We collected 179 cases of spinal cord compression MRI out of 585 spinal MRI performed, (frequency of 30.59%). The average age was 53.5 years with a male predominance (sex ratio 3.7). Motor disorders were the most common reason for examination (41%). We used the T1 T2 sagittal and T2 axial sequences. IV injection of gadolinium was performed in 48% of patients. The topographic lesions were: cervical (54.7%), thoracic (31.3%) and several segments (9.5%). The lesions concerned the compartments: extradural (79.3%), intradural (4.5%), and intramedullary (16.2%). The processes were degenerative (57.5%). tumorous (29.6%), infectious (12.3%) and vascular (0.6%). Conclusion: MRI is the benchmark imaging test for the management of non-traumatic spinal cord injury. Myelo-CT can be an alternative in the absence or in case of MRI contraindication.

关键词： Spinal Cord Compression Non Traumatic MRI Mali Hospital

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Perception and Management of Hemorroid Disease at the CSREF of the Commune Bamako Mali

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Surgical Science 2024年第2期15卷 89-97页

作者： Tounkara Cheickna Diarra mohamed Hassimy Diarra Issaka Sanogo Keita Bakary Dembele Bakary Tientigui traore Alhassane Togo Pierre Adégné Lassana Kante Department of General Surgery The Cs Ref of Commune I of Bamako Bamako Mali Department of General Surgery The Gabriel TOURE University Hospital in Bamako Bamako Mali

This work was a prospective transversal study over 6 (six) months from May 2 to December 31, 2017 at the Reference Health Center of Commune I and the Chérif la Confessional Health Center in Bamako. The aim was to study the knowledge, attitudes and behavioral practices linked to hemorrhoids in Commune I of the Bamako district, to evaluate the frequency of hemorrhoidal disease, to determine the knowledge, attitudes and behavioral practices linked to hemorrhoids among patients, their companions and traditional therapists in Commune I of the district of Bamako and the factors which influence the motivations and decisions to resort to medical-surgical care and traditional medicine in patients suffering from hemorrhoids in order to analyze the results of the management of hemorrhoidal disease at Cs Ref CI. We collected 36 patients with hemorrhoidal disease, 25 caregivers and 15 traditional hemorrhoidal disease therapists. The sex ratio was 1.25 for patients;6.5 for traditional therapists and 1.5 for accompanying people. The average age of the patients was 32.75 years;49 years for traditional therapists and 28.76 years for those accompanying them. 55.6% of patients claim to know about hemorrhoidal disease;100% of traditional therapists and 80% of accompanying people. The dietary factor of hemorrhoidal disease was mentioned by 90% of patients;66.7% of traditional therapists and 100% of caregivers. Most patients initially resorted to traditional treatment out of fear of surgery and its after-effects. The patients were treated medically and surgically.

关键词： Hemorrhoidal Disease Caregivers Traditional Therapists Patients Surgery CS Ref CI

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Evaluation of the Integrated Management Program for Acute Malnutrition in the Douentza Health District, Mopti Region, Mali

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Food and Nutrition Sciences 2024年第8期15卷 790-806页

作者： Abdoul Salam Diarra Lamine traore mohamed Diarra Tawfiq Abu Mamadou traore Yacouba Guindo Sidi Sangare Seydou Kante Intimbeye Tembine Dramane Coulibaly Mamadou Fodé Diarra Salia Keita Sadio Sambala Diallo Mamadou Samake Hamadoun Sangho National Center for Scientific and Technological Research Bamako Mali Division of Nutrition Regional Directorate of Health and Public Hygiene Mopti Mali Department of Pediatric Health Referral Center of Kalaban Coro Koulikoro Mali Private Practice for Family and Emergency Medicine Casablanca Morocco Division of Nutrition General Directorate of Health and Public Hygiene Bamako Mali Administration Department Health Referral Center of Djenne Mopti Mali Administration Department Health Referral Center of Douentza Mopti Mali Administration and Planning Department Regional Health Directorate Mopti Mali Division of Health Department Regional Health Directorate of Mopti Mopti Mali Golden Life American Hospital Bamako Mali Department of Public Health Faculty of Medicine and Odontostomatology University of Sciences Techniques and Technologies of Bamako Bamako Mali

Introduction: Malnutrition is a major public health problem in Mali, despite the efforts of the government, its technical and financial partners. The aim of this study was to evaluate the integrated management program for acute malnutrition (IMPAM). Methodology: This was a descriptive cross-sectional study that took place from January to December 2020 in the Douentza health district. The study included anyone with at least one malnourished child aged 6 to 59 months in their care who agreed to take part in the study, community health center staff who had given their consent, and the URENI manager at the Douentza reference health center. Data collected via questionnaires were entered into Excel and then analyzed using Epi-Info version 7 software. Results: A total of 138 acutely malnourished children aged 6 - 59 months, including 71 girls (51.45%), 138 accompanying mothers and 11 health workers, were included in our case study. Among the malnourished, 54.34% were in the 12 - 23 months age group and 69.57% had the severe form. 93% of the mothers interviewed were satisfied with the care provided, and all the health staff interviewed stated that community conflicts had an impact on IMPAM’s activities. Cure rates were 81% in Moderate Outpatient Nutritional Recovery and Education Unit (URENAM), 84% in Severe Ambulatory Nutritional Recovery and Education Unit (URENAS) and 92% in Recovery and Intensive Nutritional Education Unit (URENI). Drop-out rates were 19% in URENAM, 16% in URENAS and 0% in URENI. The death rate was 8% in URENI and 0% in URENAM and URENAS. Conclusion: This study confirms the high prevalence of malnutrition in the district (10.54%). It also reveals that factors such as inter-community conflict and insecurity have seriously affected the IMPAM program.

关键词： Care Acute Malnutrition Children Aged 6 - 59 Months IMPAM Douentza

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The Factors of the Failure in the Treatment of Congenital Equinus Clubfoot Varus by the Ponseti Method at the Reference Health Care Center (CSREF) of Commune III of Bamako

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Surgical Science 2023年第5期14卷 398-404页

作者： Seydou Sanogo Soumaila Diallo Boubacar Karembé Lassine Cissé Almami Kire Moussa Cissé Abdoulaye Coulibaly Aboubacar Touré Boureima Traoré Moustapha Yossi Moussa Samaké Drissa Diarra mohamed traore Seydou Mariko Mariko Issa Fomba Layes Touré Adégné Togo Department of Orthopedic-Traumatology CSREF CIII Bamako Mali

Clubfoot malformation is the most common serious congenital anomaly affecting the foot in children. Its treatment by the Ponseti method is simple, profitable and widely used in the world. Objective: The objective of this study was to identify the factors of the failure of its treatment by the Ponseti method. Material and Method: We carried out a retrospective and descriptive study of cases of congenital equinus clubfoot varus at the Reference Health Care Center of Commune III of Bamako over 26 months from September 2020 to November 2022. Data were treated with the utmost anonymity. Result: This study was performed on 44 children seen for clubfoot: male (68%) and female (32%), with a sex ratio of 2.1. We obtained 13 cases of recidivism including 7 boys and 6 girls. We found 21 cases of unilateral and 23 bilateral;among which 9 recurrences were found against 4 in the unilateral forms. 85% of recurrences did not have good adherence to the splint and 62% did not come regularly for follow-up consultation. We obtained 33 children with idiopathic clubfeet (75%) with a recurrence of 24%, and 7 children with secondary clubfeet with 71 % recurrence. There was no recurrence in the postural type. Among the recurrences, 38.5% started treatment between 1 and 6 months, 23.1% from 0 to 1 month and 15.4% at 2 years and more. 85% of recurrences had a Pirani score between 4.5 to 6 at the start of treatment and 15% at a score of 2.5 to 4. Conclusion: The factors of the failure of the Ponseti method are mainly non-compliance with treatment, secondary clubfeet, and a high Pirani score at the start of treatment.

关键词： Chess’ Factors Club Foot Ponseti Method Pirani Score

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Acute Toxicity and Anthelmintic Effects of Gomphrena serrata L. (Amaranthaceae) Extracts on Adult Worms and Eggs of Haemonchus contortus

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Pharmacology & Pharmacy 2024年第5期15卷 207-221页

作者： Hippolyte Ouedraogo mohamed Bonewendé Belemlilga Aristide traore Gilchrist Abdoul Laurent Boly Félicité Moyenga Gueswindé Geoffroy Ouedraogo Sylvain Ilboudo Lazare Belemnaba Sylvin Ouedraogo Laboratoire de Recherche-Dé veloppement de Phytom&#233dicaments et M&#233dicaments (LR-D/PM) Institut de Recherche en Sciences de la Sant&#233 (IRSS) Centre National de la Recherche Scientifique et Technologique (CNRST) Ouagadougou Burkina Faso Laboratoire de Dé veloppement du M&#233dicament (LADME) Centre de Formation deRecherche et d&#8217Expertises en Sciences du M&#233dicament (CEA-CFOREM) &#201cole Doctorale Sciences de la Sant&#233 (ED2S) Universit&#233 Joseph KI-ZERBO Ouagadougou Burkina Faso International Research Laboratory-Environnement Sant&#233 Soci&#233t&#233s (IRL 3189 ESS) CNRS/CNRST/UCAD/UGB/USTTB Ouagadougou Burkina Faso

Gomphrena serrata L. (Amaranthaceae) is a medicinal plant widely used traditionally in rural areas to treat many diseases, including gastrointestinal helminthiasis of small ruminants. This work aims to estimate the plant extracts phytochemical potential and study the activities of the aqueous decoction (GS_AD), aqueous macerate (GS_AM), and hydroalcoholic macerate (GS_HEM) of Gomphrena serrata extracts on two developmental stages (eggs and adult worms) of Haemonchus contortus. Phytochemical screening was carried out. The acute toxicity test was performed according to the Organisation for Economic Co-operation and Development (OECD) test guideline 423. The Haemonchus contortus eggs hatching inhibition test was performed left to incubate for 48 hours in the presence of the different plant extracts at increasing concentrations of 0.125;0.25;0.5;0.625;1;2;3 mg/mL. For the motility inhibition test on adult worms, the worms were contacted with the extracts at concentrations of 0.75;1;1.25;1.5;2;3;4 mg/mL and left to incubate for 24 hours. Albendazole and levamisole were used as standard. Phytochemical screening revealed the presence of tannins, saponins, reducing compounds, coumarins and derivatives, anthocyanins, steroids, triterpenes, and flavonoids. An acute toxicity study showed that the oral LD50 value of G. serrata was estimated to be 5000 mg/kg. All extracts showed an effect on both stages of parasite development. The hatching inhibition rate was 100% from 3 mg/mL for all three extracts. The rate of inhibition of motility was 100% from 4 mg/mL for each extract. HEM is more efficient on eggs and Haemonchus contortus adult worms than other extracts with IC50 of 0.457 mg/mL and LC50 of 1.329 mg/mL, respectively. These results suggest that Gomphrena serrata, a plant used by farmers, has anthelmintic properties.

关键词： Gomphrena serrata Haemonchus contortus Anthelmintic In Vitro

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Uro-Scanner Aspects of Bladder Tumours at the Mali Hospital about 17 Cases

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Open Journal of Medical Imaging 2021年第4期11卷 93-103页

作者： Mody Abdoulaye Camara mohamed Maba traore Hawa Diarra Adama Dao Boubacar Mama Toure Mamadou Ndiaye Salia Coulibaly Kone Abdoulayye Mariko Mahamane Cisse Issa Konate Moussa Ilias Guindo Konate Zakaria Nouhoum Simpara Seydou Coulibaly Néné Koumaré Siaka Sidibe Medical Imaging Department of the Mali Hospital Bamako Mali Medical Imaging Department at the CHU Gabriel Touré Bamako Mali Bamako Infirmary Hospital Bamako Mali Medical Imaging Department of the CHU Point G Bamako Mali Medical Imaging Department of CHME Luxembourg Bamako Mali Medical Imaging Department of the CHU of Kati Bamako Mali Pediatric Unit of Reference Health Center of Commune VI Bamako Mali

Introduction: Bladder tumours are frequent, have a poor prognosis and are the second most common genitourinary tumour in men. In Mali, recent statistical data on the prevalence of bladder tumours show a progression with 6.71% in 2006. The euro scanner is used in the diagnostic workup. The work was initiated in order to specify the role of the scanner in the diagnosis of these tumors. Patients and Methods: Prospective descriptive study was carried out in the medical imaging department of Mali Hospital from February to November 2018. Were included any patient with a bladder tumour on euro scanner. The patients had benefited from a preliminary preparation and a renal biological assessment in order to eliminate renal insufficiency. Our examinations were performed with a Siemens 16-slice scanner. These were axial slices performed without, with iodine injection from the pulmonary base to the pubic bones. Results: We had collected 17 patients out of 541 scans i.e. a frequency of 3.76%. The age range of 21 to 40 years was 58.8% with an average age of 25 years. The antecedents (ATCD) found were urinary bilharzia (47%) and smoking (17%). The clinic was dominated by haematuria. It was associated with a bladder mass (52%) and dysuria (23.52%). The CT scan showed a budding appearance, a size greater than 3 cm (82%), infiltration of peri-vesical fat (47.05%), and adenopathy (94%). Associated lesions were: utero-hydronephrosis (58.82%) and metastases (bone and liver in 11.76% of cases each). Conclusion: They are frequent and the history of urinary bilharziasis remains the main risk factor in endemic countries. CT scans are essential in the management of this disease. The diagnosis of certainty remains histology.

关键词： Bladder Tumour Uro-CT Mali Hospital

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Sociodemographic and Scanographic Aspects of Primary Bronchopulmonary Cancer in a Hospital in Mali

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Open Journal of Medical Imaging 2021年第4期11卷 104-114页

作者： Mody Abdoulaye Camara Moussa Abdoulaye Ouattara Hawa Diarra mohamed Maba traore Boubacar Mama Toure Nouhoum Simpara Néné Koumare Mamadou Ndiaye Salia Coulibaly Abdoulaye Kone Moussa Konate Ilias Guindo Konate Zakaria Mamadou Bakary Coulibaly Seydou Coulibaly Siaka Sidibe Department of Medical Imaging of the Mali Hospital Bamako Mali Department of Thoracic Surgery of the Mlai Hospital Bamako Mali Pediatric Unit at the Common Reference Health Center VI Bamako Mali Department of Medical Imaging of the CHU of Kati Bamako Mali Bamako Infirmary Hospital Bamako Mali Medical Imaging Department of CHME Luxembourg Bamako Mali Department of Gynecology of the Mali Hospital Bamako Mali

Summary: A malignant tumour that develops from the bronchial epithelium and then invades the lungs. It ranks third after colorectal and breast cancer. In Mali, computed tomography (CT) is the main imaging tool used at all stages of treatment. We had initiated this study with the objective of specifying the place of CT in the diagnosis of primary bronchopulmonary cancer at the hospital of Mali. Method: This is a prospective and descriptive study conducted by the Medical Imaging and Thoracic Surgery departments at Mali Hospital from March 2014 to February 2015. All the patients who have benefited from a CT scan and presenting at least one histologically confirmed bronchopulmonary tumor were included. Results: We were recruiting 60 patients with bronchopulmonary cancers out of 500 referred for a thoracic CT scan performed, a frequency of 12%. There was one male patient with a sex ratio of 4H/1F. The average age was 60 years. The history of smoking was 85%. The symptoms were dominated by general condition (63.33%), cough (25%) and haemoptysis (58.33%). CT scans were performed in all patients. The lesions were located more in the lower lobes (71%). The tumours were: heterogeneous tissue density (70%), spiculated contours (80%), and the histology was more non-small cell carcinoma. Conclusion: The incidence of bronchopulmonary cancer is very high and its prognosis is poor at an advanced stage. The evaluative role of CT and biopsy guidance has given it a place of choice in its management. The diagnosis of certainty remains histology.

关键词： Sociodemographic and Scanographic Aspects of Primary Bronchopulmonary Cancer in a Hospital in Mali

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