tbuckley/cabot-search huggingface dataset:
Progress in intestinal permeability related diseases and its influencing factors
Authors: Panpan Xing, Ping Liu, Junping Wang
Journal: BMJ (2017)

The intestinal permeability is crucial for human health, and the changes of intestinal permeability may cause variety of diseases, which is widely concerned. This article reviews the latest research progress in the relationship between intestinal permeability and diseases, the main influencing factors of intestinal permeability and its common testing methods, which may provide new ideas for the clinical treatment of related diseases.


Key words: 
Gastrointestinal tract; Permeability; Influencing factor
Spectrum of Frontotemporal Lobar Degeneration on 18F-FDG PET/CT Scan
Authors: Nikhil Seniaray, Ritu Verma, Rajeev Ranjan, Ethel Belho, Vanshika Gupta, Harsh Mahajan
Journal: Clinical Nuclear Medicine (2020)

Abstract FTLD (Frontotemporal lobar degeneration) is a clinically and pathologically heterogeneous group of degenerative disorders, characterized by predominantly asymmetric degeneration of frontal and temporal lobes with selective neuronal loss and gliosis. The disease presents with variable degrees of impairment in behavior, language, executive control, and motor symptoms with progressive loss of cognition. On the basis of presenting clinical symptoms, FTLD is further divided into behavioral variant, nonfluent/agrammatic variant primary progressive aphasia (PPA), semantic variant PPA, logopenic variant PPA, progressive supranuclear palsy, and corticobasal ganglionic degeneration. Here we illustrate the utility of FDG PET with statistical parametric analysis for evaluation of these patients.
Effects of Cook balloon cervical dilator on full-term nulliparous parturients under epidural analgesia
Authors: Wangping Zhang, Yinfa Zhang, Xiaoyu Zhu, Shaoping Zhong, Yujuan Cai
Journal: BMJ (2015)

To explore the feasibility and effects of Cook balloon cervical dilator on full-term nulliparous parturients under epidural analgesia. The observation group(n=40)received Cook balloon cervical dilation under epidural analgesia. However, the control group (n=40) had no epidural analgesia. Latent phase of labor was shorter in observation group than that in control group [(198.7±65.7) vs. (242.9±78.9) min, P<0.05]. And the incidence of cesarean section and perineal laceration was lower under epidural analgesia(8% vs. 15%, 45% vs. 50% respectively). There were no effects on success rate of induced labor in neither group. Cook balloon could shorten latent phase of labor, relieve the pain of parturients and increase no infection rate [leukocyte count: (8.82±2.74) ×109 /L vs. (9.10±3.06) ×109/L, C-reactive protein: (4.73±0.87) mg/L vs. (4.82±0.90) mg/L respectively]. It is worth wider clinical popularization.


Key words: 
Labor, induced; Analgesia, obstetrical
Correlation of MYC gene signature variations with clinical response to fimepinostat in patients with aggressive B-cell lymphoma.
Authors: Jefferson Parker, Dena Grayson, Reinhard W. Von Roemeling
Journal: Journal of Clinical Oncology (2020)

e15654 Background: Fimepinostat (F), a small molecule dual inhibitor of PI3K α, β, and δ isoforms and Class I and II histone deacetylases (HDACs), is currently under investigation for the treatment of aggressive hematological cancers. Preclinical studies demonstrated that F both decreases transcription of myc and MYC-targeted genes (via HDAC inhibition) and increases destruction of MYC protein (via PI3K inhibition). This study sought to identify differences in transcript-level signatures of gene networks in pre-treatment tumor samples associated with future clinical response to F. Methods: Among 105 patients (pts) with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated in phase 1/2 clinical trials of F (± rituximab), 33 pts had pre-treatment tumor biopsy samples available for molecular testing. All pts had measurable disease at baseline and had at least 1 post-baseline tumor assessment. To be included in the analysis set, pts must have been on study for ≥42 days. RNA libraries were created and sequenced on the Illumina HiSeq platform. Gene Set Enrichment Analysis (GSEA; Subramanian et al., 2005) was used to study changes in transcript expression patterns that correlate with responder (complete/partial response) or non-responder (progressive disease) pt populations. ~20,000 genes were rank-ordered by log 2 -fold change and tested against the MSigDB (Liberzon et al., 2011) collection of gene expression signatures. Results: &gt; 1500 Gene Sets with False Discovery Rate (FDR) &lt; = 0.05 and Normalized Enrichment Score (NES) &gt; 1.3 for genes upregulated in the F-responder population were identified. These Gene Sets represent transcriptional activity associated with well characterized biological pathways or gene expression signatures determined empirically. The top 20 signatures by NES were associated with general transcription functions (E2F, RNA polymerase), chromosomal structure (meiotic recombination, telomere maintenance) and specifically, MYC transcription targets (NES: 2.7; FDR q-val: 0). Additional signatures consistent with PI3K (GSK3b) and HDAC activity in the responder population were also identified, as would be expected for a dual inhibitor of PI3Ks and HDACs. Conclusions: GSEA analysis of genes upregulated in the F-treated responder DLBCL pts are consistent with preclinical data showing that F functions to suppress MYC in tumor cells. F is currently undergoing active clinical study in combination with venetoclax for the treatment of R/R DLBCL or high grade B-cell lymphoma (HGBL): NCT01742988.
Reducing the vertical transmission of HIV
Authors: B. A Gbolade, K H Tan, K P Teo, B. Essex, M. A Waldron, E. Foley, V Harindra, M. Goodman, A. Olaitan, S. Madge, M. Jones, M. Johnson, F. Parazzini, E. Ricci, P. Grasso, M. Surace, G. Benzi, P. de Zulueta
Journal: BMJ (1998)

Editor—The editorial by Mercey focuses on testing pregnant women attending antenatal clinics as the main means of reducing the vertical transmission of HIV.1 Most pregnant women seeking induced abortions would not have attended antenatal clinics.
The impact of endogenous estrogen exposure on the characteristics of estrogen receptor (ER) positive, early-stage breast cancer (EBC).
Authors: Orly Yariv, Rinat Yerushalmi, Assaf Moore, Tzippy Shohat, Dalia Tsoref, Hadar Goldvaser
Journal: Journal of Clinical Oncology (2020)

e12605 Background: Menstrual and parity history might impact the risk for ER positive breast cancer. Data on the impact of these factors on other tumor characteristics are limited. Methods: A single center retrospective cohort study comprising all women with ER positive, human epidermal growth factor receptor 2 (HER2) negative, EBC whose tumors were sent to OncotypeDX analysis and were treated in our institute between 2005 to 2012. Data on endogenous estrogen exposure were collected including: age of menarche and menopause, number of deliveries and age of first delivery. Subsequently, data on pre-specified clinical and histopathological features were collected including: tumor size, nodal status, ER and progesterone receptor (PR) staining, grade, Oncotype recurrence score (RS), ki67, lymphovascular and perineural invasion. The impact of endogenous estrogen exposure was evaluated by multiple comparisons including: early age of (&lt;12 years) compared to older age of menarche, nulliparity compared to women who had at least one delivery, multiparty (≥5 deliveries) compared to other, late age of first delivery (≥30 years) compared to other and postmenopausal compared to premenopausal. In postmenopausal women the age of menopause was also assessed using early age of menopause (&lt;45 years) and late age of menopause (&gt;55 years). Results: A total of 620 women were included. 79% were postmenopausal, median age of menarche was 13 (range 9-17) and median number of deliveries was three (range 0-14). Post-menopausal women were more likely to have stronger ER intensity (79% vs. 65%, p=0.002) and less likely to have high (≥31) RS (8% vs. 16%, p=0.021), but PR negativity was significantly more frequent (16% vs. 7%, p=0.007. Additionally, early age of menarche was associated with PR positivity (94% vs. 85%, p=0.039).). No other associations were found between endogenous estrogen exposures and tumor characteristics. Conclusions: These findings suggest that premenopausal women with luminal EBC might have more aggressive disease. Large scale studies are needed to elucidate the impact of endogenous estrogen on luminal breast cancer.
Clinical problems about mastoplasia
Authors: 王水, 陈琳
Journal: BMJ (2009)

尽管乳腺增生症(hyperplastic disease of breast)是女性多发病,最常见于30～45岁之间,约占乳腺门诊疾病的80%左右.但迄今为止,该病仍然有许多悬而未决的问题,诸如该病的流行病学;病因及发病机制;诊断和治疗标准等等,这些问题都有待于进一步深入和系统的研究.本文仅就以下与临床关系密切的几个问题进行讨论。
胰岛素强化治疗
Authors: 王昕, 邢小燕
Journal: BMJ (2011)

高血糖是糖尿病最直接的病生化特征,也是导致患者发生急慢性并发症的高危因素,有效控制血糖可以改善病情、减少并发症发生、发展已成共识.伴随着此认识,胰岛素强化治疗模式受到了广泛的关注.一、胰岛素强化治疗的基本概念胰岛素强化治疗就是采用多次皮下胰岛素注射(MSII)或持续皮下胰岛素输注(CSII)治疗模式,尽量模拟正常人体生理性胰岛素分泌节律,使血糖控制至正常或接近正常水平。
Annual trends in opioid prescribing for patients (Pts) with metastatic non-small cell lung cancer (mNSCLC): Cancerlinq data analysis, 2010 to 2017.
Authors: Judith A. Paice, Li Chen, Elizabeth Garrett-Mayer, Karen S Hagerty, Kristina Lynne Maletz Novick, Danielle Potter, Mark Riffon, Whitney Rhodes, Liya Wang, Suanna S. Bruinooge
Journal: Journal of Clinical Oncology (2020)

2076 Background: Despite opioid misuse and abuse, opioids remain a mainstay for management of cancer pain. Government, payers, and institutions have implemented policies to reduce opioid use. The impact of these restrictions on oncologist prescriptions (Rx) of opioids and management of cancer pain in pts with cancer is not well known. Methods: A retrospective, observational analysis used deidentified EHR data from ASCO’s CLQ Discovery database. Study cohort included pts with mNSCLC diagnosis and &gt;1 clinical encounter (including opioid Rx) from CLQ clinician during 2010-2017. Opioids included DEA schedule II and III opioid drugs prescribed for cancer pain, excluding cough suppressants. Annual Rx rates were defined as the number of mNSCLC pts who had ≥ 1 opioid Rx dated 2010-2017 per CLQ total mNSCLC pts who had ≥1 clinical encounter in the year. Annual rates demonstrate trends in opioid prescribing patterns over time. Results: 18,106 pts with mNSCLC clinical activity between 2010 and 2017 were identified. Overall, 39.8% of pts had opioid Rx in 2010-2017. Annual Rx rates increased from 2010-2015 and fell 2016-2017 (see table). Hydrocodone was the second most frequently prescribed opioid overall (N=4211 pts), but Rx rates began to decline in 2012. Tramadol and acetaminophen + codeine Rx rates gradually increased throughout the time period. DEA initially scheduled Tramadol as schedule IV in 2014. Conclusions: Opioids are commonly prescribed by oncologists for patients with mNSCLC. Rx rates have declined since 2015, likely due to increased government, payer, and institutional restrictions on access. Hydrocodone Rx declined since 2012, perhaps exacerbated by reclassification from schedule III to schedule II by the DEA (October 2014). Rxs for schedule IV and III opioids (known to be of lower potency) increased modestly, likely due to comparatively fewer prescribing restrictions. Additional research is needed to understand whether the decline continues and the impact on management of cancer pain, particularly among metastatic patients. [Table: see text]
Genomic and immune intratumor heterogeneity in gastric linitis plastica.
Authors: Jin Huang, Guofeng Zhao, Qiu Peng, Jian Ma, Pansong Li, Lianpeng Chang, Yan-Fang Guan, Alexandre Reuben, Xuefeng Xia, Xin Yi, Jianjun Zhang, Zihua Chen
Journal: Journal of Clinical Oncology (2020)

e16518 Background: Gastric linitis plastica (LP) is a rare and aggressive type of gastric cancer (GC) for which the genomic landscape and architecture have gone largely undescribed. Methods: 4 LP patients were enrolled. 10 region tumor samples of each LP patient and matched peripheral blood were collected. Matched blood cells of each patient were also collected for removing germline background Whole-exome sequencing(WES), TCR sequencing, TCGA gastric cancer and several WES articles data were used to investigate intra and inter patient genomic and immune heterogeneity. Results: All 4 LP patients were female and were in stage III. LP biopsies were sequenced with median 290.6x effective depth. A total of 11,504 somatic mutations including 6,339 non-silent mutations were identified. The median non-silent tumor mutation burden (TMB) of biopsy samples was 3.23 mutations/Mb (range from 1.36 to 4.88), which was comparable to gastric adenocarcinoma(p = 0.3). Phylogenetic trees of 4 LP patients demonstrated clear evidence of branched evolution, and the phylogenetic trees varied extensively across the four cases. The percentages of trunk mutations of 4 LP were 12.8%, 5.4%, 5.4% and 30.7%, respectively, while the proportions of trunk neoantigens were 6.2%, 2.2%, 12% and 12.4, respectivelyWhen comparing LP to other multiregion WES studies, e.g., lung adenocarcinoma, renal cell carcinoma, and esophageal squamous cell carcinoma, LP was one of the most heterogeneous tumor types. The top mutational signatures in this cohort associated with spontaneous deamination, DNA mismatch repair (MMR), and small indels at repeats etc. Furthermore, profound TCR ITH was observed in all 4 LP patients. None of the T cell clones were shared among all tumor regions and 94.23-94.41% T cells were restricted to individual tumor regions. To quantify the TCR ITH, we utilized the Morisita overlap index (MOI), which ranged from 0.34 to 0.56 across different regions within the same tumors suggesting marked inter-individual TCR repertoire heterogeneity and profound intratumor TCR heterogeneity. Conclusions: Based on whole-exome sequencing and TCR sequencing, we demonstrate that LP is highly heterogeneous for mutations, neoantigens and T cells, which contributes to its poor prognosis.
Diagnostic efficiency of postprandial plasma glucose and oral glucose tolerance test in patients with metabolic disorders
Authors: Yuan Gao, Hong-wen Zhou, Tao Yang, Wei Tang
Journal: BMJ (2012)

A total of 1342 individuals underwent physical examinations according to the criteria of metabolic syndrome of International Diabetes Federation (IDF) in 2005.And 314 patients with metabolic disorders were screened for diabetes by standard meal and methods oral glucose tolerance test (OGTT).Newly diagnosed diabetics was 12 (4.1％ ) vs.17 (5.8％) respectively.No significant difference existed between two methods (P =0.332).Kendall's (τ)b =0.313,Kendall's (τ)c =0.208 and Gamma coefficient =0.580 (P =0.000).The mixed meal method was correlated with OGTT,Kappa =0.258 (P =0.000) and two methods were consistent.Diabetic screening should be stressed in the subjects with metabolic abnormalities.And the detecting efficiency of postprandial plasma glucose is similar to OGTT.

Key words: 
Diabetes ;  Diagnosis
Questionnaire survey on accreditation standards for trainers of general practitioners in community health centers
Authors: Yao Liu, Xiangjie Zhang, Jing Zhou, Liyang Zhang, Shanzhu Zhu
Journal: BMJ (2015)

Objective
To study the application of accreditation standards for trainers of general practitioners (GPs) in community health centers.


Methods
The questionnaire was designed according to the accreditation standards for GP trainers in community health centers, which involved professional quality, clinical competence in primary care and teaching abilities.According to typical sampling, 583 trainers from 56 community teaching bases in Shanghai were selected for the survey.


Results
Among 583 participants, the effective respondents were 505 with a response rate of 86.6%.The professional quality was highly recognized by the participants, and more than 80% of trainers met the requirement.For the ability of primary care, 81.4%(411/505), 79.8% (403/505) and 69.5% (351/505) of participants were well qualified with the abilities of management for hypertension, type 2 diabetes and coronary heart disease, respectively, while only about 40% had abilities of management for epilepsy, hypothyroidism and chronic mental diseases.75.4% (381/505) participants fully mastered the principle of first aid skills and CPR, while only 24.8% (125/505) had abilities of management for conjunctival foreign body and nasal foreign body, 34.5% (174/505) had the abilities of debridement and gastrolavage.For the index of teaching abilities, most trainers had insufficient teaching capacity and experience in the community.Only 48.5% (245/505) and 40.2% (203/505) of trainers were familiar with the teaching methods of cased-based learning and problem-based learning, respectively.Significant difference was found in the scores of teaching abilities among trainers from community health centers in different locations(P 0.5).


Conclusion
The trainers of general practitioners in community health centers meet the requirement of accreditation standards in the aspects of professional quality and clinical competences in primary care, while the teaching abilities remained to be improved and should be strengthened in the future.


Key words: 
Teacher training; Questionnaires; General practitioner
Heart failure management during the <scp>COVID</scp>‐19 outbreak in Italy: a telemedicine experience from a heart failure university tertiary referral centre
Authors: Andrea Salzano, Roberta D'Assante, Francesca M. Stagnaro, Valeria Valente, Giulia Crisci, Federica Giardino, Michele Arcopinto, Eduardo Bossone, Alberto M. Marra, Antonio Cittadini
Journal: European Journal of Heart Failure (2020)
Extracorporeal shock wave therapy for enthesiopathy
Authors: Wei Sun, Zirong Li
Journal: BMJ (2019)

体外震波又称体外冲击波，是一种具有力学特性的声波，通过振动、高速运动等导致介质极度压缩，从而聚集产生能量。体外震波在肩关节钙化性肌腱炎、肱骨外上髁炎、大转子疼痛综合征、髌腱炎、跟腱炎和足底筋膜炎等末端病治疗中具有良好的疗效。
Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with <i>PIK3CA-</i>mutated (mut) hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) previously treated with cyclin-dependent kinase 4/6 inhibitor (CDKi) + aromatase inhibitor (AI): BYLieve study results.
Authors: Hope S. Rugo, Florence Lerebours, Eva Ciruelos, Pamela Drullinsky, Manuel Ruiz Borrego, Patrick Neven, Yeon Hee Park, Aleix Prat, Thomas Bachelot, Dejan Juric, Nicholas C. Turner, Nickolas Sophos, Juan Pablo Zarate, Christina Arce, Yu-Ming Shen, Stephen K. L. Chia
Journal: Journal of Clinical Oncology (2020)

1006 Background: PIK3CA mutations (mut) occur in ~40% of pts with HR+, HER2– ABC and are associated with poor prognosis and resistance to treatment (tx). ALP, a PI3Kα inhibitor, plus FUL demonstrated efficacy in the phase 3 SOLAR-1 trial of HR+, HER2– PIK3CA-mut ABC. Little clinical data and few prospective studies are available to inform tx decisions for pts with HR+, HER2– PIK3CA-mut ABC in the post-CDKi setting. BYLieve is the first trial evaluating ALP + endocrine therapy (ET; FUL or letrozole) in pts with HR+, HER2– PIK3CA-mut ABC who progressed on/after prior therapy, including CDKi. In this ongoing phase 2, open-label, noncomparative study, 112 pts with centrally confirmed PIK3CA mut in tumor tissue are enrolled in each cohort per immediate prior tx of CDKi + AI, CDKi + FUL, or systemic chemo or ET. Enrollment is complete in prior CDKi + AI and CDKi + FUL cohorts and ongoing in prior systemic chemo or ET cohort. We report on the cohort of pts with CDKi + AI as immediate prior tx. Methods: Pts received ALP 300 mg/day + FUL 500 mg Q28D + C1D15. Primary endpoint was proportion of pts alive without disease progression at 6 mo per local assessment; 2-sided 95% confidence intervals (CI) were calculated using Clopper and Pearson (1934) exact method. Evidence of clinically meaningful tx effect was defined as the lower bound of the 95% CI &gt; 30%. Safety was assessed in all patients; AEs presented by preferred term. Results: 127 pts whose immediate prior tx was CDKi + AI were enrolled, of whom 121 had centrally confirmed PIK3CA mut; median follow-up was 11.7 mo. Primary endpoint was met: proportion of pts without disease progression at 6 mo was 50.4% (95% CI, 41.2-59.6). Most frequent all-grade AEs were diarrhea (60%), hyperglycemia (58%), nausea (46%), fatigue (29%), decreased appetite (28%), and rash (28%). Most frequent grade ≥3 AEs included hyperglycemia (28%), rash (9%), and rash maculopapular (9%). Incidence of AEs leading to discontinuation was low; most frequent AEs leading to discontinuation were rash (5 pts, 3.9%), colitis, hyperglycemia, urticaria, and vomiting (2 pts, 1.6% each). Conclusions: With follow-up still ongoing, BYLieve shows in a large number of pts that ALP + FUL demonstrates clinically meaningful efficacy and manageable toxicity post CDKi tx. Building on findings from SOLAR-1, BYLieve further supports use of ALP + FUL for HR+, HER2– PIK3CA-mut ABC. Clinical trial information: NCT03056755 .
Efficacy and tolerance of chemotherapy with dacarbazine or temozolomide associated or not with 5-fluorouracil (5-FU) in endocrine carcinomas: A retrospective multicentric study from the Groupe des Tumeurs Endocrines (GTE)
Authors: S. Pecout, E. Baudin, A. Paoli, F. Maire, E. Terrebonne, E. Mitry, M. Pavel, P. Ruszniewski, G. Cadiot, H. Brixi-Benmansour
Journal: Journal of Clinical Oncology (2009)

e15523 Background: Small studies have shown that therapy with dacarbazine and temozolomide give up to 34% tumoral response rates in endocrine carcinomas. The aim of this large retrospective multicentric study was to evaluate efficacy and tolerance of chemotherapy with dacarbazine or temozolomide associated or not with 5-FU in endocrine carcinomas. Methods: Patients were recruited in 6 French and 1 German centers. All patients with well (WDEC) or poorly-differentiated endocrine carcinoma (PDEC), whatever the primary, and who have been treated with dacarbazine or temozolomide associated or not with iv 5-FU or capecitabine, were included. Response rates were evaluated according to RECIST criteria by one of the investigator and toxicity according to National Cancer Institute Common criteria. Results: 86 patients were included : 36 women, median age 61.7 years (27.7 - 85.7), 67 WHO-PS 0–1. Primaries were : pancreas (n=34), digestive tract (n=23), thyroid (n=9), lung (n=6), other (n=6), unknown (n=8). 64 patients had WDEC and 11 PDEC (11 not determined). The number of previous systemic treatments (chemotherapy, chemoembolization, radionuclide therapy) was: 0 (n=16), 1 (n=25), 2 (n=25), 3 (n=14), 4 and more (n=6). Treatments received were : dacarbazine (n=3), temozolomide (n=19), dacarbazine + 5-FU (n=48), temozolomide + capecitabine (n=16). Evaluation was impossible in two patients. Tumoral response rates (partial and stabilization) were 61.2% in WDEC and 18.2% in PDEC. The best response rates in WDEC were : partial response (n=6; 9.7%), stabilization (n=32; 51.6%), progression (n=24; 38.7%) without significant differences between regimens and primary location. Response rates in WDEC were 88.9%, 71.4% and 64.7% in first, second and third line therapies, respectively. Median progression free survival in WDEC was 5.7 months (0.1–41.7). Grade 3–4 toxicities were hematologic (n=8), digestive (n=10), infection (n=3). Conclusions: Dacarbazine and temozolomide therapy showed high partial response and stabilization rates up to 3rd line therapy in well-differentiated endocrine carcinoma, with moderate toxicity. MGMT tumoral status is currently investigated. No significant financial relationships to disclose.