tbuckley/cabot-search huggingface dataset:
Ethnic diversity in infant gut microbiota is apparent before the introduction of complementary diets
Authors: Jia Xu, Blair Lawley, Gerard Wong, Anna Otal, Li Chen, Toh Jia Ying, Xinyi Lin, Wei Wei Pang, Fabian Yap, Yap-Seng Chong, Peter D. Gluckman, Yung Seng Lee, Mary Foong-Fong Chong, Gerald W. Tannock, Neerja Karnani
Journal: Gut Microbes (2020)

The human gut microbiota develops soon after birth and can acquire inter-individual variation upon exposure to intrinsic and environmental cues. However, inter-individual variation has not been comprehensively assessed in a multi-ethnic study. We studied a longitudinal birth cohort of 106 infants of three Asian ethnicities (Chinese, Malay, and Indian) that resided in the same geographical location (Singapore). Specific and temporal influences of ethnicity, mode of delivery, breastfeeding status, gestational age, birthweight, gender, and maternal education on the development of the gut microbiota in the first 2 years of life were studied. Mode of delivery, breastfeeding status, and ethnicity were identified as the main factors influencing the compositional development of the gut microbiota. Effects of delivery mode and breastfeeding status lasted until 6M and 3M, respectively, with the primary impact on the diversity and temporal colonization of the genera Bacteroides and Bifidobacterium. The effect of ethnicity was apparent at 3M post-birth, even before the introduction of weaning (complementary) foods, and remained significant after adjusting for delivery mode and breastfeeding status. Ethnic influences remained significant until 12M in the Indian and Chinese infants. The microbiota of Indian infants was characterized by higher abundances of Bifidobacterium and Lactobacillus, while Chinese infants had higher abundances of Bacteroides and Akkermansia. These findings provide a detailed insight into the specific and temporal influences of early life factors and ethnicity in the development of the human gut microbiota.Trial Registration: Clinicaltrials.gov registration no. NCT01174875.
Phase I/II study of avadomide (CC-122) in combination with R-CHOP for newly diagnosed DLBCL.
Authors: Neha Mehta-Shah, Julio C. Chavez, Pau Abrisqueta, Nathalie Johnson, Juan Miguel Bergua Burgues, Carlos Grande-Garcia, Douglas Stewart, Kieron Dunleavy, Guillermo Rodriguez, Juan-Manuel Sancho, James Drew, Chengqing Wu, Patrick R. Hagner, Richard Delarue, Alejandro Martin
Journal: Journal of Clinical Oncology (2020)

3501 Background: In certain subsets of patients (pts) with diffuse large B-cell lymphoma (DLBCL), the failure rate of standard R-CHOP treatment is high. Pts with high-risk disease (International Prognostic score [IPI] 3-5) have a particularly poor prognosis, with 3-y survival rates of ~62% with R-CHOP alone. The cereblon E3 ligase modulator avadomide (CC-122) showed activity in pts with relapsed or refractory DLBCL. We report results of avadomide plus R-CHOP in previously untreated pts with high-risk DLBCL. Methods: CC-122-DLBCL-002 (NCT03283202) is a phase 1/2 study of avadomide plus R-CHOP-21 in pts newly diagnosed with DLBCL not otherwise specified with IPI scores 3-5 who were aged ≥18 y. Pts received standard R-CHOP and escalating doses (1-3 mg) of oral avadomide for up to six 21-d cycles (Table). All pts received pegfilgrastim support. Primary objectives were to assess safety, tolerability, and complete response (CR) rate. Secondary objectives include evaluation of additional efficacy parameters (objective response rate [ORR], progression-free survival [PFS], and overall survival) and biomarkers. Results: As of July 30, 2019, 35 pts were enrolled in the phase 1 part of the study. Median age was 66 y (range, 20-75), 23 pts (66%) were aged &gt; 60 y, 18 (51%) had an IPI score of 3, and 17 (49%) had an IPI score of 4-5. Thirty-two pts (91%) completed 6 cycles of treatment. Median relative total dose intensity of avadomide was 99% and the average relative dose intensity of R-CHOP was 95%. Six pts had dose-limiting toxicities: 1 pt had neutropenia and bacterial hepatic infection; 1 had pneumonia; 1 had febrile neutropenia (FN); 1 had FN and hypotension; 1 had FN due to skin infections; and 1 had sepsis. The recommended phase 2 dose was 3 mg 2/3 wk. Grade 3/4 adverse events in ≥10% of pts were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and FN (11%). Among 34 efficacy-evaluable pts, the ORR was 88% (n = 30/34), including a CR rate of 79% (n = 27/34) at the end of treatment. With a median follow-up of 10 mo, the 1-y PFS rate was 80% (95% CI, 58-92). Correlative analyses will be presented at the meeting. Conclusions: Avadomide plus R-CHOP was well-tolerated with no significant additive toxicities. The promising efficacy in this high-risk pt population warrants further evaluation of immunomodulatory drugs combined with immunochemotherapy for pts with previously untreated DLBCL. Clinical trial information: NCT03283202 . [Table: see text]
Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping
Authors: Paula R. Clemens, Vamshi K. Rao, Anne M. Connolly, Amy D. Harper, Jean K. Mah, Edward C. Smith, Craig M. McDonald, Craig M. Zaidman, Lauren P. Morgenroth, Hironori Osaki, Youhei Satou, Taishi Yamashita, Eric P. Hoffman
Journal: JAMA Neurology (2020)

An unmet need remains for safe and efficacious treatments for Duchenne muscular dystrophy (DMD). To date, there are limited agents available that address the underlying cause of the disease.To evaluate the safety, tolerability, and efficacy of viltolarsen, a novel antisense oligonucleotide, in participants with DMD amenable to exon 53 skipping.This phase 2 study was a 4-week randomized clinical trial for safety followed by a 20-week open-label treatment period of patients aged 4 to 9 years with DMD amenable to exon 53 skipping. To enroll 16 participants, with 8 participants in each of the 2 dose cohorts, 17 participants were screened. Study enrollment occurred between December 16, 2016, and August 17, 2017, at sites in the US and Canada. Data were collected from December 2016 to February 2018, and data were analyzed from April 2018 to May 2019.Participants received 40 mg/kg (low dose) or 80 mg/kg (high dose) of viltolarsen administered by weekly intravenous infusion.Primary outcomes of the trial included safety, tolerability, and de novo dystrophin protein production measured by Western blot in participants' biceps muscles. Secondary outcomes included additional assessments of dystrophin mRNA and protein production as well as clinical muscle strength and function.Of the 16 included boys with DMD, 15 (94%) were white, and the mean (SD) age was 7.4 (1.8) years. After 20 to 24 weeks of treatment, significant drug-induced dystrophin production was seen in both viltolarsen dose cohorts (40 mg/kg per week: mean [range] 5.7% [3.2-10.3] of normal; 80 mg/kg per week: mean [range] 5.9% [1.1-14.4] of normal). Viltolarsen was well tolerated; no treatment-emergent adverse events required dose reduction, interruption, or discontinuation of the study drug. No serious adverse events or deaths occurred during the study. Compared with 65 age-matched and treatment-matched natural history controls, all 16 participants treated with viltolarsen showed significant improvements in timed function tests from baseline, including time to stand from supine (viltolarsen: -0.19 s; control: 0.66 s), time to run/walk 10 m (viltolarsen: 0.23 m/s; control: -0.04 m/s), and 6-minute walk test (viltolarsen: 28.9 m; control: -65.3 m) at the week 25 visit.Systemic treatment of participants with DMD with viltolarsen induced de novo dystrophin production, and clinical improvement of timed function tests was observed.ClinicalTrials.gov Identifier: NCT02740972.
Effect of long-term treatment combined with fosinopril and indapamide on insulin resistance and glucose tolerance in patients with essential hypertension
Authors: 章建梁, 秦永文, 郑兴, 郑国龙, 刘明, 赵仙先, 陈少萍, 郭冀珍
Journal: BMJ (2004)

目的 研究长期联合应用福辛普利和吲哚帕胺对高血压患者胰岛素抵抗(IR)、血糖和血脂代谢等的影响. 方法124例轻中度高血压患者随机分为观察组(福辛普利和吲哚帕胺联合治疗)和对照组(单用福辛普利),92例完成研究(观察组48例,对照组44例),服药14个月,观察胰岛素敏感指数(ISI)、血压、血糖、血脂、血钾等的变化.结果观察组降压总有效率显著高于对照组(97.9% 比75.0%,P<0.01),治疗后ISI显著下降(55±16比48±13,P<0.05),血糖和血脂升高;其中29例患者停服吲哚帕胺后,ISI显著升高(P<0.01),血糖和血脂改善.对照组治疗后ISI显著升高(52±16比59±19,P<0.01),血糖和血脂改善.结论联合应用福辛普利和吲哚帕胺比单用福辛普利能更有效降低血压,但长期应用可加重高血压患者IR,恶化血糖和血脂代谢.而单用福辛普利能改善高血压患者胰岛素敏感性,改善血糖和血脂代谢.提示吲哚帕胺可诱发糖尿病,停服后部分患者糖耐量损害可以逆转。
消化科临床精粹(二)
Authors: 吴东, 朱峰, 陈嘉林
Journal: BMJ (2010)

一、回盲部溃疡最常见于三类疾病:肠结核、克罗恩病、淋巴瘤 回盲部肠黏膜淋巴组织丰富,是某些疾病的好发部位.其中克罗恩病和肠结核临床及内镜表现十分类似,容易造成混淆,但两者仍有一些不同之处可资鉴别:①肠结核可有肠外结核表现,女性可出现闭经;②肠结核并发肠瘘和出血几率少于克罗恩病;③肠结核造成升结肠挛缩以及回盲瓣破坏比克罗恩病更明显;④病变单纯累及盲肠者多考虑结核,单纯累及回肠者多考虑克罗恩病;⑤肠结核的溃疡多为环形.而克罗恩病多为纵行,可有铺路石征.二者实在难以鉴别时,可酌情先予试验性抗结核治疗~([1])。
Impact of doxycycline on outcomes in AL amyloidosis.
Authors: Brandon Jamaal Blue, Lauren Duncanson, Doris K. Hansen, Yumeng Zhang, Hien D Liu, Taiga Nishihori, Jose L. Ochoa-Bayona, Rachid C. Baz
Journal: Journal of Clinical Oncology (2020)

e20568 Background: It has been shown in mouse models doxycycline(Doxy) interferes with amyloid fibril formation. Retrospective data suggests the addition of Doxy to standard chemotherapy(chemo) reduces mortality in cardiac amyloidosis. We examined the relationship between Doxy use, treatment, and OS in a cohort of AL Amyloidosis(AL) within an academic center. Methods: AL pts between 2008 and 2020 at Moffitt Cancer Center. For this study we included patients with AL, with all types of organ involvement. We excluded pts with non-AL Amyloidosis and pts with localized amyloidosis were excluded. Data on organ involved, organ response, date of death, treatment were obtained for each pt. OS was defined as time from AL diagnosis to date of death. Univariate comparisons were performed to identify differences in treatment and other prognostic variables between Doxy groups, where appropriate (Table). Results: 209 pts that met inclusion criteria, 13 pts(6%) had cardiac involvement with AL. Of those 13 pts, only 3 pts(23%) received Doxy in addition to standard of care chemo. For this study, we included all types of AL for total 209 pts. Of the 209 pts, 9.5% received Doxy in addition to standard of care chemo and 90.5% pts did not receive Doxy and had chemo alone. Pts who received Doxy had more proteinuria (suggesting more significant renal involvement) but other characteristics were not statistically different including cardiac biomarkers (table). A numerically higher rate of organ response (67% versus 43%) was noted in patients who received Doxy but this didn’t reach statistical significance. Further the OS was numerically higher for Doxy treated pts however again this didn’t meet statistical significance. Conclusions: We noted higher organ responses and overall survival in Doxy treated pts, we could not identify statistical differences in outcomes possibly because of the sample size. Nevertheless, further follow up is warranted and Doxy may be associated with improved outcomes in AL. [Table: see text]
以腹痛为突出表现的伤寒性心内膜炎一例
Authors: 宋道远, 翟秀军, 方儒修
Journal: BMJ (2005)

患者男,55岁,商人,因稽留高热(39.7～40.8℃)伴阵发性寒战、干咳、恶心、呕吐、腹泻11 d于2002年8月5日入院.发热前4 d因牙痛行拔除术.曾采用头孢舒克、氨苄青霉素、头孢唑啉钠、安痛定、地塞米松等治疗.既往无心脏病史.查体:体温40.6℃,脉搏99次/min,呼吸26次/min,血压110/70 mm Hg(14.6/9.3 kPa);急性热病容,表情淡漠,皮肤、巩膜重度黄染,未见淤点、Osler结节、Janeway损害、Roth点和杵状指(趾),两中、下肺可闻及湿性啰音;心率99次/min,律齐,心尖部可闻及3/6级收缩期杂音;肝下缘于右肋缘下锁骨中线处约3 cm,缘钝质中无触痛,脾肋下刚触及;余无阳性发现。
The therapeutic value of ERCP and EST on choledocholithiasis
Authors: Jian-feng Yang, Xiao Zhang, Xiao-feng Zhang, Ying-hui Guo, Wen L, Xiu-ying Lin
Journal: BMJ (2010)

1263 patients with choledocholithiasis were treated with endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) from January 2005 to December 2008, with 1235 (97.8%) cases successfully treated. One-time ERCP removal of the stones was successful in 982 patients, with two times in 129 patients and three times in 124. 1130 patients (89. 5% ) underwent endoscopic nasal biliary drainage (ENBD) after the procedure. 56 patients with refractory stone were treated with intrabiliary plastic stent, among whom 42 were cured through endoscopic retrograde biliary drainage (ERBD) of 1 -3 times. Complications occurred in 29 patients (2. 3% ) with hemorrhage in 8 patients,acute pancreatitis in 17 and perforations in 4. Mortality rate was 0. We concluded that the majority cases of choledocholithiasis can be successfully treated by ERCP, while intrahepatic cholelithiasis and refractory common bile duct stone remained therapeutic challenges. It is also mandatory to evaluate long-term efficacy and complications of ERCP.

Key words: 
Choledocholithiasis;  Cholangiopancreatography,endoscopic retrograde
Comparative efficacy and acceptability of psychotherapies for acute anxiety disorders in children and adolescents: study protocol for a network meta-analysis
Authors: 张玉清, 周新雨, James Anthony C, 覃彬, Whittington Craig J, Cuijpers Pim, Giovane Cinzia Del, 刘艺昀, Cohen David, R Weisz John, 谢鹏
Journal: BMJ (2016)
Circulating tumor cells (CTCs) with small-cell like pathology are prevalent in metastatic castration-resistant prostate cancer (mCRPC) and show selective pharmacodynamic reductions in patients treated with platinum but not ARSI or taxane.
Authors: Howard I. Scher, Adam Jendrisak, Audrey Gill, Ethan Barnett, Anuradha Gopalan, Samir Zaidi, Hannah Benoliel, Emily Carbone, Jiyun Byun, Joseph Schonhoft, Rick Wenstrup
Journal: Journal of Clinical Oncology (2020)

5572 Background: The increasing availability and earlier use of life prolonging drugs targeting the androgen receptor signaling axis (ARSI) has resulted in an increase in the frequency of late state tumors with “small cell/neuroendocrine (NESC) phenotypes” similar to small-cell lung cancer (SCLC). Definitive pathologic criteria to diagnose the “entity” are lacking, and the eligibility criteria across trials are inconsistent, limiting the ability to relate outcomes between studies. We hypothesized that an analytically valid assay for a rigorously defined “small-cell CTC” phenotype might serve as a unifying biomarker for the presence of NESC-like tumors in an individual for use in clinical trials. Methods: Using the WHO guidelines for small-cell diagnosis in tissue as reference, we defined an equivalent set of single-cell CTC criteria for defining a CTC with small-cell histology: a small and circular CD45-, CK+ cell with high N/C ratio lacking detectable nucleoli. Small-cell subtype pharmacodynamic changes were studied in 233 patients with progressing mCRPC about to start an AR signaling inhibitor ARSi (N=111), taxane (N=89), or platinum (N=33). Results: CTCs with small-cell morphology had lower AR protein expression compared with non-small-cell CTCs (P&lt;0.0001) and increased with therapy line. The small-cell CTC subtype decreased in number from baseline to on-therapy in patients treated with platinum but not in those treated with ARSi or taxane (Table). Conclusions: Digital pathology analysis of CTCs defined a CTC subtype consistent with that of small-cell carcinoma that were only reduced in number with platinum-based therapy. The tracking of CTC subtypes after treatment with different drug classes may help assess drug activity in heavily treated patients that often have heterogeneous disease that of which may not be captured using standard measures of response. [Table: see text]
慢性阻塞性肺疾病的危险因素和早期预防
Authors: 徐永健
Journal: BMJ (2004)

慢性阻塞性肺疾病(COPD)的病因目前尚未完全阐明,因此,其早期预防比较困难.通过研究发现多种因素与COPD的发病率增高有关,这些危险因素大致可以分为外因(即环境因素)与内因(即个体易患因素)两类。
A helper-dependent adenoviral vector rescues CFTR to wild-type functional levels in cystic fibrosis epithelial cells harbouring class I mutations
Authors: Huibi Cao, Hong Ouyang, Onofrio Laselva, Claire Bartlett, Zhichang Peter Zhou, Cathleen Duan, Tarini Gunawardena, Julie Avolio, Christine E. Bear, Tanja Gonska, Jim Hu, Theo J. Moraes
Journal: European Respiratory Journal (2020)

Cystic fibrosis (CF) is a genetic disorder affecting multiple organs, including the pancreas, hepatobiliary system and reproductive organs; however, lung disease is responsible for the majority of morbidity and mortality. Management of CF involves CF transmembrane conductance regulator (CFTR) modulator agents including corrector drugs to augment cellular trafficking of mutant CFTR as well as potentiators that open defective CFTR channels. These therapies are poised to help most individuals with CF, with the notable exception of individuals with class I mutations where full-length CFTR protein is not produced. For these mutations, gene replacement has been suggested as a potential solution. In this work, we used a helper-dependent adenoviral vector (HD-CFTR) to express CFTR in nasal epithelial cell cultures derived from CF subjects with class I CFTR mutations. CFTR function was significantly restored in CF cells by HD-CFTR and reached healthy control functional levels as detected by Ussing chamber and membrane potential (FLIPR) assay. A dose–response relationship was observed between the amount of vector used and subsequent functional outcomes; small amounts of HD-CFTR were sufficient to correct CFTR function. At higher doses, HD-CFTR did not increase CFTR function in healthy control cells above baseline values. This latter observation allowed us to use this vector to benchmark in vitro efficacy testing of CFTR-modulator drugs. In summary, we demonstrate the potential for HD-CFTR to inform in vitro testing and to restore CFTR function to healthy control levels in airway cells with class I or CFTR nonsense mutations.
Application of intracavitary three-dimensional ultrasonography in the diagnosis of polycystic ovary syndrome
Authors: Jia-qi Hu, Hua Shi, Rui-qiang Guo, Li-dan Hao, Min-yi Zhu
Journal: BMJ (2010)

To evaluate the application of intracavitary three-dimensional ultrasonography in the diagnosis of polycystic ovary syndrome ( PCOS). The three-dimensional volumes of ovary were measured by intracavitary ultrasonography in 40 PCOS patients and 40 normal controls. The diagnostic value of parameters derived from three-dimensional ultrasonography was evaluated by using the receiver operating characteristic (ROC) curve. The ovarian volume, stromal volume, and the stromal/total volume ratio in PCOS group were significantly higher than those in control group (both P ＜ 0. 05 ) ; the area under ROC curve ( AUC ) of them were 0. 876, 0. 926, 0. 886 respectively. Among these parameters, stromal volume had the highest diagnostic value for PCOS, the cut-off value of which was 7.52 cm3 with a sensitivity of 88% and a specificity of 90%. Volume parameters of ovary measured by intracavitary three-dimensional ultrasonography can offer quantitative information for the diagnosis of PCOS.

Key words: 
Ultrasonography;  Polycystic ovary syndrome
Analgesic effect of nimesulide in withdrawing nasal packing after endoscopic sinus surgery
Authors: Jing Jin, Lin-feng Ye, Peng Song, Xu-hong Zhou
Journal: BMJ (2008)

Sixty four patients undergoing endoscopic sinus surgery were randomly divided into two groups.In nimesulide group (n=32) patients were given nimesulide capsule 100 mg after surgery and 32 patients in control group were given 100 mg vitamin C as placebo.The visual analogue scale (VAS) was used to evaluate the degree of pain during withdrawing nasal packing.The VAS value of the nimesulide group was 2.8±1.1 3 h after surgery and 2.7±1.2 during with drawing nasal packing,that of control group was 6.7±0.6 and 8.3±0.6,respectively (both P<0.01).The results revealed that nimesulide had a siguificant analgesic effect in endoscopic sinus surgery.

Key words: 
Anti-inflammatory,agents; Analgesics
A survey on current status of clinicians in community health-care service centers of three cities in China
Authors: 全国全科医学专业技术队伍现状研究课题组
Journal: BMJ (2009)

Objective To understand current status and problems existed among clinicians workforce in several community health-care service centers of China to provide evidence for relevant policy-making. Methods Sixty-two community health-care service centers were selected from two districts each in Tianjin, Nanjing and Wuhan Cities, respectively, for the survey with questionnaire and focus group discussion. Results ①Fifty-eight of 62 community health-care service centers surveyed (93.5 percent) were qualified as a legal entity, 60 (96.8 percent) registered as medical insurance institutions designated by government, and 59 (95.2 percent) were state-owned or run by state-owned hospitals. All the 60 institutions provided service in public health and essential medical care for communities and were economically running relatively good. ②There were totally 1664 registered clinicians with an average age of 45 years ( and a standard deviation of 11 ), 942 of them ( 56.6 percent) at age above 45, 406 ( 24.4 percent) at age below 35, and 1166 (70.1 percent) with college education. ③Thirty-eight of 874 clinicians with medium or senior professional titles (4.4 percent) were qualified as general practitioners (GPs). ④Five hundred and thirty-eight of 1024 licensed clinicians or assistant clinicians (52.5 percent) were registered as internists for permit to practice medicine, and 65 registered as GPs (6.3 percent). There were totally 257 GPs in general practice clinics and 45 of them registered as GPs (17.5 percent) for permit to practice medicine. ⑤One hundred and five clinicians were promoted in the past three years and 17 of them were registered as GPs (16.2 percent). ⑥Three hundred and fifty-four clinicians were temporarily employed (21.3 percent) of those in service. Conclusions ①A lot of clinicians at general practice consultation rooms in community health-care service centers practiced medicine often beyond their duties registered. ②Few clinicians extended their willingness to be promoted as GPs, with too lower percentage of them taking promotion examinations. ③The number of GPs was in short obviously and quality of GPs was poor in general with their relatively older age.④It is suggested that more investment should be input, relevant policies perfected, attraction to GP position increased, human resource management and legal management of GPs strengthened, and non-registered practicing behavior should be eliminated by government.

Key words: 
Community health center; Questionnaires; Interviews; General practitioner
Liver diseases in adult-onset Still's disease
Authors: Jian-zhong Liu, Yan-fang Liu, Guang-lan Zhang, Xiao-lei Wang, Ju-peng Tan, Ming Han
Journal: BMJ (2009)

Clinical data of 108 patients with adult-onset Still's disease(AOSD)were analyzed.The results showed that 56 patients(51.9%)developed liver damage and abnormal liver functioil(alanine aminortransferase and aspartate aminortransferase were significantly increased).Gender,age,time from disease onset to confirmed diagnosis,fever,rash,arthritis,pharyngeal pain,splenomegaly,lymphadenopathy,anemia,leukocvtosis,thrmbocytosis,and increased erythrocyte sedimentation rate,serum C-reactive protein,and serum iton protein showed no significant difierence between the two groups (P＞0.05).Clinical symptoms of liver damage were atypical.Among the 56 patients with liver damage,8 were presented with gastrointestinal symptoms,and 24 showed enlarged liver iu B.ultrasound examination.Our results suggest the prevalence of liver damage in AOSD patients may be hiSh,which could attribute to the disease itself and the medication.The patients would expect good response to corticosteroid treatment and satisfactory outcomes.

Key words: 
Still's diseases,adult.onset; Liver diseases