tbuckley/cabot-search huggingface dataset:
MicroRNA analysis of childhood atopic dermatitis reveals a role for miR‐451a*
Authors: J. Nousbeck, M.A. McAleer, G. Hurault, E. Kenny, K. Harte, S. Kezic, R.J. Tanaka, A.D. Irvine
Journal: British Journal of Dermatology (2020)

MicroRNAs (miRNAs), important regulators of gene expression, have been implicated in a variety of disorders. The expression pattern of miRNAs in paediatric atopic dermatitis (AD) has not been well studied.We sought to investigate miRNA expression profiles in different blood compartments of infants with AD.Small RNA and analysis with the HTG EdgeSeq system were performed to identify differentially expressed miRNAs in peripheral blood mononuclear cells (PBMCs) and plasma of infants with AD vs. age-matched healthy controls, with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) used for validation and measurement of miRNA targets. Logistic regression models with area under the receiving operating characteristic estimation was used to evaluate the diagnostic potential of chosen miRNAs for AD.RNA sequencing was performed to access miRNA expression profiles in paediatric AD. We identified 10 differentially expressed miRNAs in PBMCs and eight dysregulated miRNAs in plasma of infants with AD compared with controls. Upregulated miRNAs in PBMCs included miRNAs known to be involved in inflammation: miR-223-3p, miR-126-5p and miR-143-3p. Differential expression of only one miRNA, miR-451a, was observed in both PBMCs and plasma of children with AD. Dysregulation of three miRNAs (miR-451a, miR-143-3p and miR-223-3p) was validated in larger numbers of samples and miR-451a was identified as a predictive biomarker for the early diagnosis of the disease. Experimentally verified targets of miR-451a, interleukin 6 receptor (IL6R) and proteasome subunit beta type-8 (PSMB8), were increased in patients with AD, negatively correlated with miR-451a levels and upregulated following inhibition of miR-451a in PBMCs.In infants with AD, a distinct peripheral blood miRNA signature is seen, highlighting the systemic effects of the disease. miR-451a is uniquely expressed in different blood compartments of patients with AD and may serve as a promising novel biomarker for the early diagnosis of AD.
Effectiveness evaluation on an intervention model of reproductive health among unmarried women migrants in Qingdao: a community trial
Authors: Cui-ping Wang, Jia-hua Wan
Journal: BMJ (2011)

Objective To study knowledge,ability and related behavior of reproductive health among unmarried women migrants in Qingdao area,Shandong and evaluate effectiveness of basic intervention,including provision of free condom and health education and enhanced intervention,including healthy sex,contraception and health-care seeking behavior.Methods A community intervention trial was conducted among 1800 unmarried women migrants aged 18 -29 years in 10 workplaces of Qingdao.Basic intervention included health knowledge publicity and distribution of free condoms,and enhanced intervention included distribution of very important person (VIP) service cards,hotline telephone service,broadcasting digital versatile disc (DVD) of reproductive health knowledge,health lectures,peer education,and so on,in addition to health knowledge publicity and distribution of free condoms.Effectiveness was evaluated using questionnaire before and six months after intervention.Results After intervention,awareness of reproductive health and attitude to reproductive health improved significantly among the women migrants,as compared to those before intervention,particularly in knowledge of contraception and sexual health with enhanced intervention (with more than 20％ of them aware) ( P ＜ 0.01 ).About effectiveness on health-care seeking behavior,59.2％ (482/814) and 80.8％ (651/806) of the women migrants with reproductive tract infections would visit physicians after basic and enhanced intervention,as compared to those of 32.0％ (286/895) and 31.9％ (275/862) before them,respectively (P＜0.01).About effectiveness on contraceptive behavior,persistent and proper use of effective contraception methods improved significantly after intervention,as compared to that before it ( P ＜ 0.05 ),but with no significant difference between the two group with basic and enhanced intervention.Conclusions Both basic and enhanced intervention is effective and feasible in women migrants,more effective for enhanced one.

Key words: 
Reproductive health service; Residential mobility; Single person; Outcome assessment
Bgb-A425, an investigational anti-TIM-3 monoclonal antibody, in combination with tislelizumab, an anti-PD-1 monoclonal antibody, in patients with advanced solid tumors: A phase I/II trial in progress.
Authors: Jayesh Desai, Tarek Meniawy, Brandon Beagle, ZheZhen Li, Song Mu, John Wu, Crystal S. Denlinger, Wells A. Messersmith
Journal: Journal of Clinical Oncology (2020)

TPS3146 Background: While immune surveillance plays a critical role in preventing tumor proliferation and metastasis, tumors develop resistance mechanisms to suppress and/or escape the immune system. T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and programmed cell death protein-1 (PD-1) function as immune checkpoint receptors on tumor-infiltrating lymphocytes. Overlap in expression and function suggests TIM-3 and PD-1 cooperate to maximize effector T-cell exhaustion, leading to a decreased antitumor immune response. Although blockade of TIM-3 alone is unlikely to result in an efficacious antitumor immune response, combined TIM-3/PD-1 blockade may enhance the antitumor properties of anti-PD-1 therapies alone. BGB-A425 is an investigational IgG1-variant monoclonal antibody against TIM-3. Tislelizumab, an anti-PD-1 antibody, was engineered to minimize binding to FcɣR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. This phase 1/2 study will assess the safety/tolerability, pharmacokinetic (PK) profile, and antitumor activity of BGB-A425 in combination with tislelizumab in patients with advanced solid tumors. Methods: This is an open-label phase 1/2 study (NCT03744468) of BGB-A425 in combination with tislelizumab in patients with histologically/cytologically confirmed advanced, metastatic, unresectable solid tumors. Phase 1 will determine the recommended phase 2 dose (RP2D) for combination treatment; phase 2 will assess the antitumor effects of the combination in select tumor types. In phase 1, up to 42 patients will be enrolled into sequential cohorts of increasing doses of intravenous (IV) BGB-A425 in combination with tislelizumab 200 mg IV, based on a 3+3 study design. During Cycle 1, patients will receive BGB-A425 alone on Day 1 followed by tislelizumab alone on Day 8. If no dose-limiting toxicities are observed, patients will receive both BGB-A425 and tislelizumab sequentially on Day 29 and every 21 days thereafter. Once the RP2D is determined, the combination therapy will be evaluated in up to 120 patients with select tumor types in phase 2. Safety/tolerability profile and RP2D determination (phase 1) and objective response rate per RECIST v1.1 (phase 2) are primary objectives; secondary objectives include antitumor activity, PK profile, and immunogenicity of combination therapy. Clinical trial information: NCT03744468 .
Adjuvant chemotherapy after concurrent chemoradiation therapy for locally advanced cervical cancer.
Authors: Lingna Kou, Tao Zhang, Siyun Peng, Yifei Wang, Mingyang Yuan, Minmin Li
Journal: Journal of Clinical Oncology (2020)

6031 Background: Standard treatment nowadays for locally advanced cervical cancer (LACC) is concurrent chemoradiation therapy (CCRT). However, due to distant metastasis, survival outcomes are still not optimistic. We tried to evaluate the clinical efficacy and safety of adjuvant chemotherapy for patients with LACC after treated with concurrent chemoradiation therapy (CCRT). Methods: Patients diagnosed between May, 2013 to May, 2018 with stage IIA-IIIB LACC were retrospectively analyzed. All the patients received platinum-based radical concurrent chemoradiotherapy and were divided into two groups: adjuvant chemotherapy after CCRT (CCRT+ACT group) and observation after CCRT (CCRT group). Overall survival (OS), progression free survival (PFS) and adverse effects were recorded and analyzed. Kaplan–Meier method and log-rank test were used to calculate and compare differences between survival outcomes. Toxicities were analyzed using chi-square test. Results: In total, 375 patients were included in this study, and 262 patients accepted ACT after CCRT while the remaining 113 patients chose to observe. With a median follow-up of 40 months (range 5-73 months), no significant differences were found in both overall survival (OS) and progression free survival (PFS) between two groups referring as 88.5% vs. 90.3% ( P= 0.904) and 83.2% vs. 87.6% ( P= 0.374). OS rates for patients in CCRT+ACT and CCRT groups at 1 year and 3 years were 97.3% vs. 94.7% ( P= 0.195) and 90.2% vs. 88.4% ( P= 0.694), respectively. Meanwhile, PFS rates at 1 year and 3 years were 92% vs. 94.7% ( P= 0.371) and 87.5% vs. 85.5% ( P= 0.761) for two arms separately. 3-4 grades acute adverse events happened more frequently in CCRT+ACT group than in CCRT group, with significant differences in neutropenia and anemia ( P &lt;0.05). Conclusions: In this study, adjuvant chemotherapy after concomitant chemoradiotherapy did not show benefit of survival but do induce adverse effects. We do not suggest it unless further large scale randomized controlled trials are executed to verify it.
PD-L1 tumor proportion score and clinical benefit from first-line pembrolizumab in patients with advanced nonsquamous versus squamous non-small cell lung cancer (NSCLC).
Authors: Deborah Blythe Doroshow, Wei Wei, Jon Zugazagoitia, Charles Jack Robbins, Swati Gupta, Blythe J.S. Adamson, David L. Rimm
Journal: Journal of Clinical Oncology (2020)

9539 Background: The predictive value of PD-L1 tumor proportion score (TPS) on NSCLC tumor cells as a biomarker for response to PD-(L)1 inhibitors is well established. However, its histology specific value in advanced (a) squamous (Sq) versus nonsquamous (NS) cancers remains unclear. Here, we used real world data to assess the differential value of PD-L1 TPS as a predictive biomarker for overall survival (OS) after first-line pembrolizumab (P) in patients (pts) with Sq versus NS NSCLC. Methods: Inclusion criteria for this analysis of the Flatiron Health EHR-derived de-identified database required that pts were diagnosed with aNSCLC, tested for PD-L1 TPS and received a numerical result, had no alteration in EGFR, ALK, or ROS, and received first-line, single agent P. The primary endpoint was overall survival (OS) from the first dose of P in patients with TPS ≥ 50% (H) compared to patients with TPS &lt; 50% (L). Due to the violation of the proportional hazards assumption, a generalized gamma model of OS was used, adjusting for demographic variables and estimated median OS and their confidence intervals with the bootstrap method. The PD-L1-histology interaction was examined by comparing the differences in median OS (H vs. L) between Sq and NS patients. Results: Of 1560 pts with NSCLC treated from 1/2011 – 5/2019, 1055 had NS and 405 Sq. No meaningful differences in age, gender, or smoking history were seen between PD-L1 H and L pts with either histology. Among NS pts, H had significantly longer OS than L, with unadjusted hazard ratio (HR) of 0.71 (95% CI: 0.53 - 0.94; p = 0.018). Among Sq pts, H was not associated with longer OS than L, with unadjusted HR 0.89 (95% CI: 0.64 - 1.25; p = 0.514). Based on the generalized gamma model, PD-L1 H in Sq patients was associated with a 0.19 year improvement in median OS (95% CI: -0.22-0.49, P = 0.283), whereas PD-L1 H in the NS group was associated with a 0.70 year improvement in OS (95% CI: 0.34-1.05, P &lt; 0.001). The median improvements between the Sq and NS patients were significantly different (P = 0.034), after adjusting for demographic variables. Conclusions: PD-L1 TPS of ≥ 50% predicted longer OS in pts with NS NSCLC treated with first-line P compared to pts whose tumors had a TPS of &lt; 50%. However, no relationship between PD-L1 TPS and OS after first-line P was seen in patients with Sq NSCLC. These data suggest that PD-L1 may not be an appropriate predictive biomarker for checkpoint inhibitor use in NSCLC with squamous histology.
The study of atorvastatin combined with hydration to prevent contrast-induced nephropathy
Authors: Xiao-bo Zhang, Feng-ying Tang, Gui-hua Wang, Li-qin Zhang, Wei-wei Yang, Xiao-qi Ji
Journal: BMJ (2011)

One hundred patients with chronic renal failure(CRF) undergoing contrast diagnosis and/or interventional therapy were randomly divided into two groups: patients in hydration alone group( n = 49 )received intravenous infusion of 0.9% sodium chloride 12 h before injection of contrast media till 12 h after examination (hydration), patients in atorvastatin plus hydration group (n = 51 ) received atorvastatin 80mg/d 24 h before examintion for 3 d in addition to hydration.The serum creatinine concentrations were measured before and 48 h after injection of contrast media.In atorvastatin plus hydration group, the incidence rate of contrast-induced nephropathy (CIN) was 8% (4/51), which was significantly lower than that of hydration group (24%,12/49 )(P＜0.05).Short-term and large dose administration of atorvastatin plus hydration can decrease the incidence of CIN in patients with chronic renal failure undergoing contrast diagnosis and/or interventional thrapy.

Key words: 
Nephrosis;  Antilipemic agents
Factors associated with axillary conversion after neoadjuvant chemotherapy in initially node positive breast cancer patients: A transSENTINA analysis.
Authors: Hans-Christian Kolberg, Thorsten Kühn, Maja Krajewska, Ingo Bauerfeind, Tanja N. Fehm, Barbara Fleige, Gisela Helms, Annette Lebeau, Annette Staebler, Sibylle Loibl, Michael Untch, Cornelia Kolberg-Liedtke
Journal: Journal of Clinical Oncology (2020)

567 Background: Current study concepts in early breast cancer after neoadjuvant chemotherapy (NAT) are aiming at reducing morbidity by omission of axillary surgery in selected patients. Selection criteria for this strategy have to include the probability of conversion from cN1 to ycN0. We analyzed the association of clinical/pathological parameters and axillary conversion with data from arms C and D of the SENTINA trial (Kühn T et al., Lancet Oncol 2013). Methods: Patients were recruited to Arms C/D of the SENTINA trial in case they presented with clinically positive nodes before NAT. Based on their response to NAT they were then assigned to either arm C (clinically conversion to ycN0) or arm D (no clinical conversion (ycN+). In both the pre- and post-NAT scenarios, clinically involved lymph nodes were defined as palpable and/or suspect by ultrasound. Univariate logistic regression analyses were carried out to evaluate the association between clinical/pathological parameters and axillary conversion after NAT. Results: Of the 892 patients in arms C and D of the SENTINA trial 716 were evaluable for this analysis. After NAT, 593 patients converted to ycN0 and were therefore assigned to arm C; in contrast, 123 patients still had involved lymph nodes after NAT (ycN+) and were assigned to Arm D. Arms C and D were compared regarding the clinical/pathological parameters tumor diameter by ultrasound before and after NAT, grading, multifocality, ER status, PR status, HER2 status, pathological complete remission in the breast (breast pCR), morphology, lymphovascular invasion (LVI) and hemangiosis. Only small tumor diameter after NAT (p = 0.0038), achievement of breast pCR (p = 0.0001) and lack of LVI (p = 0.0009) were positively associated with axillary conversion from cN1 to ycN0 after NAT. Conclusions: Because of the small patient number in arm D, we were not able to identify an association between parameters of tumor biology (ER, PR, HER2 and TN status) and axillary conversion. However, favorable response of the primary tumor (represented both clinically by tumor diameter after NAT and pathologically by pCR in the breast) were positively associated with conversion from cN1 to ycN0. These results justify including patients with clinical and pathological response of the primary tumor in trials investigating de-escalation of axillary surgery after NAT.
儿童过敏性结膜炎患者血清总IgE及特异性IgE的研究
Authors: 乔彤, 胡义珍, 艾洪武, 李世莲
Journal: BMJ (2007)

采用酶联免疫吸附试验检测256例儿童过敏性结膜炎患者血清总IgE及特异性IgE,其中检测吸入性过敏原230例,检测食入性过敏原200例.结果 表明,两者的总IgE阳性率达99.2%(254/256);吸入组所检测的14项过敏原中特异性IgE总阳性率为93.5%,以尘螨、粉螨阳性率最高;食入组在所检测的12项过敏原中出现特异性IgE总阳性率51.0%,以鱼和蟹虾最高;常年性过敏性结膜炎、春季角结膜炎和特应性角结膜炎主要以尘螨、粉螨以及屋尘为主;季节性过敏性结膜炎主要以树花粉、蒿草为主.4种过敏性结膜炎主要为鱼、蟹虾食入性过敏原。
Missed opportunities? A retrospective analysis of lung cancer screening utilization among patients with lung cancer.
Authors: Coral Olazagasti, Nina Kohn, Karen Aviles, Matthew Ehrlich, Aldane Hoilett, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2020)

e13565 Background: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Tobacco smoking is implicated as the causative factor in 85% of LC. The U.S. Preventive Services Task Force (USPSTF) and National Comprehensive Cancer Network (NCCN) recommendations for annual low-dose CT chest (LDCT) for LC screening in high risk adults who meet appropriate criteria, which primarily focuses on age and smoking history. Medicare coverage for LC screening for eligible individuals went into effect in February 2015. Despite this, screening rates remain low and patients with LC are typically diagnosed at a later stage. We conducted a single center retrospective analysis of patients with established diagnosis of lung cancer to evaluate if screening guidelines were appropriately followed prior to the cancer diagnosis. Methods: Patients diagnosed with LC between 2016 and 2019 were included in the analysis. Charts were reviewed for demographics, detailed smoking history, as well as histology and stage of LC. Associations between categorical factors and screening and were examined using the chi-square test. Associations between continuous and ordinal factors and screening and were examined using the Mann-Whitney test. Results: A total of 530 charts were reviewed. Of those, 52.5% (278) met NCCN and/or USPSTF criteria and 10.8% (30/278) underwent screening. The median age for those who were screened was 69 years. There was no association between age at diagnosis and screening. There was a significant association between active smoking status and screening (p &lt; 0.0191). An average of 16.8% (16/95) of current smokers and 7.7% (14/183) of former smokers were screened. Patients who had screening CT scans were diagnosed at earlier stages of LC compared to those who were not screened (p &lt; 0.0083) [table]. Conclusions: Our study showed that despite established guidelines for LC screening and insurance coverage, a vast majority of screening-eligible LC patients have never had LDCT. We found that patients who underwent screening as per guidelines were diagnosed at earlier stages of disease compared to those not screened, which goes along with published data. Ongoing efforts to increase awareness and adherence to LC screening guidelines will be of paramount importance in improving early detection and reducing mortality from LC. [Table: see text]
The chemo-brain effect in colorectal cancer patients.
Authors: Matilda Lee, Wan Qin Chong, Hon Lyn Tan, Gloria Chan, Jingshan Ho, Raghav Sundar, Cheng Ean Chee, Fatima Nasrallah, Edward H Koo, Wei-Peng Yong
Journal: Journal of Clinical Oncology (2020)

e24095 Background: The chemo-brain effect associated with systemic chemotherapy results in cognitive disturbances impacting the capacity to engage in tasks and quality of life (QOL). Patients with colorectal cancer (CRC) who receive adjuvant chemotherapy generally have long survival times. The long-term effect of chemotherapy on cognition is uncertain. We aimed to ascertain the frequency of long-term cognitive impairment using neuropsychological assessments and correlating with neuroimaging. Methods: In this prospective pilot study, patients (n=22) with stage II to III CRC between 45 to 75 years old, who were planned to receive adjuvant chemotherapy, were recruited. 3 visits were scheduled for each subject – pre-chemotherapy (V1), at 1 month post chemotherapy (V2), and at 6 months post chemotherapy (V3). Serial tests were performed – the Cambridge Neuropsychological Test Automated Battery (CANTAB), QOL questionnaires (Hospital Anxiety and Depression Scale (HADS), Perceived Deficits Questionnaire (PDQ), EORTC QLQ-C30, FACT-ES), 3 item pocket smell test, functional PET/MRI brain imaging, and blood biomarker studies. Results: 18/22 subjects (13 male, 5 female) had completed tests at all 3 visits; the median age was 62 years (range 51 – 69). 9/18 had an initial decline (median -0.033) of Rapid Visual Information processing (RVP) at V2; 3/9 showed improvement to baseline at V3. 8/18 had a persistent decline in RVP scores at V3 (median -0.054). This was associated with increased HADS depression scores (mean 3.63 at V2 vs 4.63 at V1), worsening attention scores (mean 4.38 at V3 and 3.63 at V1), prospective memory scores (mean 3.75 at V3 vs 3.38 at V1), and total scores (mean 14.63 at V3 vs 13.75 at V1) on the PDQ. 7/18 had an increase in Paired Associates Learning (PAL) errors (median +6) at V2. 3/7 improved to baseline at V3, while 4/7 continued to have a persistent decline. PAL scores were not associated with worsening retrospective or prospective PDQ memory scores, changes in HADS depression or EORTC QLQ-C30 scores. There was no difference in baseline CANTAB scores for patients reporting declining vs stable QLQ-C30 scores. Conclusions: Only half of patients with initial RVP A and PAL decline improved at 6 months post chemotherapy. Further efforts should be placed to identify those at risk of poor recovery, and develop strategies to manage the chemo-brain effect. The correlation of cognitive decline with neuroimaging will be presented in the final analysis.
Incidence of and risk factors for hospitalizations from chemotherapy among patients with stage III and stage IV colorectal cancer.
Authors: April Falconi, Ezra Fishman, John Barron, Michael Eleff, Michael Jordan Fisch, Winnie Chi
Journal: Journal of Clinical Oncology (2020)

e16090 Background: Despite the decreasing colorectal cancer (CRC) mortality rate over the past decade, complications from CRC treatment remain a challenge. Prior research has shown that a majority of patients with stage III CRC in the adjuvant setting experience hospitalizations due to chemotherapy-related toxicity. Minimal research, however, has examined risk factors of these events and the prevalence of hospitalization among stage IV CRC patients. Methods: We used claims data from a geographically-diverse private health insurer—including both commercially-insured and Medicare Advantage patients—to estimate and characterize risk factors of hospitalizations among Stage III or IV CRC patients. We compared sociodemographic, clinical, as well as provider characteristics and cancer treatment regimens between patients with and without hospitalizations from the initiation of chemotherapy to 60 days after the end of chemotherapy. Results: Incidence rates for hospitalization from chemotherapy were 49% and 70% for stage III and IV CRC patients, respectively. Although the oldest stage III CRC patients (age 75+) were the most likely to experience hospitalizations, the youngest age group (age 18-49) of stage IV patients experienced the highest incidence (74%) of hospitalizations (p &lt; 0.05). Higher values of the Elixhauser comorbidity index was associated with a higher risk for hospitalizations among patients with stage III CRC (p &lt; 0.001). Both stage III and stage IV patients with diabetes were more likely (p &lt; 0.05) to have hospitalizations from chemotherapy (55% and 73%, respectively). Conclusions: Hospitalization from chemotherapy is very common among stage III and IV CRC patients. These data identify subgroups at higher risk. Study findings may inform choice of cancer treatment regimen and focus on key underlying medical needs