tbuckley/cabot-search huggingface dataset:
Outcomes After Use of a Lymph Node Collection Kit for Lung Cancer Surgery: A Pragmatic, Population-Based, Multi-Institutional, Staggered Implementation Study
Authors: Raymond U. Osarogiagbon, Matthew P. Smeltzer, Nicholas R. Faris, Meredith A. Ray, Carrie Fehnel, Phillip Ojeabulu, Olawale Akinbobola, Meghan Meadows-Taylor, Laura M. McHugh, Ahmed M. Halal, Paul Levy, Vishal Sachdev, David Talton, Lynn Wiggins, Xiao-Ou Shu, Yu Shyr, Edward T. Robbins, Lisa M. Klesges
Journal: Journal of Thoracic Oncology (2021)

Suboptimal pathologic nodal staging prevails after curative-intent resection of lung cancer. We evaluated the impact of a lymph node specimen collection kit on lung cancer surgery outcomes in a prospective, population-based, staggered implementation study.From January 1, 2014, to August 28, 2018, we implemented the kit in three homogeneous institutional cohorts involving 11 eligible hospitals from four contiguous hospital referral regions. Our primary outcome was pathologic nodal staging quality, defined by the following evidence-based measures: the number of lymph nodes or stations examined, proportions with poor-quality markers such as nonexamination of lymph nodes, and aggregate quality benchmarks including the National Comprehensive Cancer Network criteria. Additional outcomes included perioperative complications, health care utilization, and overall survival.Of 1492 participants, 56% had resection with the kit and 44% without. Pathologic nodal staging quality was significantly higher in the kit cases: 0.2% of kit cases versus 9.8% of nonkit cases had no lymph nodes examined; 3.2% versus 25.3% had no mediastinal lymph nodes; 75% versus 26% attained the National Comprehensive Cancer Network criteria (p < 0.0001 for all comparisons). Kit cases revealed no difference in perioperative complications or health care utilization except for significantly shorter duration of surgery, lower proportions with atelectasis, and slightly higher use of blood transfusion. Resection with the kit was associated with a lower hazard of death (crude, 0.78 [95% confidence interval: 0.61-0.99]; adjusted 0.85 [0.71-1.02]).Lung cancer surgery with a lymph node collection kit significantly improved pathologic nodal staging quality, with a trend toward survival improvement, without excessive perioperative morbidity or mortality.
Overexpression of EZH2 in Multiple Myeloma Is Associated with Poor Prognosis Regardless of Treatment with Novel Agents or High-Dose Chemotherapy
Authors: Mark A. Schroeder, Mark A. Fiala, Armin Ghobadi, Keith E. Stockerl-Goldstein, Tanya M. Wildes, Ravi Vij
Journal: Blood (2017)
Evaluation of Optimal Diastolic Blood Pressure Range Among Adults With Treated Systolic Blood Pressure Less Than 130 mm Hg
Authors: Jingen Li, Virend K. Somers, Xiang Gao, Zhuo Chen, Jianqing Ju, Qian Lin, Essa A. Mohamed, Shahid Karim, Hao Xu, Lijing Zhang
Journal: JAMA Network Open (2021)

Extremely low diastolic blood pressure has been reported to be associated with increased adverse cardiovascular events (ie, the diastolic J-shape phenomenon); however, current US guidelines recommend an intensive blood pressure target of less than 130/80 mm Hg without mentioning the lower limits of diastolic blood pressure.
Lysosomal hydrolases of the epidermis.
Authors: P.D. MIER, JOSE J.M.A. HURK
Journal: British Journal of Dermatology (1975)

Four distinct peptide hydrolases (EC 3-4) have been characterized in guinea-pig epidermis; these are cathepsin B1, cathepsin C, cathepsin D and arylamidase. Their properties are consistent with those of lysosomal enzymes. Cathepsin E was not detected.
POMC neuronal heterogeneity in energy balance and beyond: an integrated view
Authors: Carmelo Quarta, Marc Claret, Lori M. Zeltser, Kevin W. Williams, Giles S. H. Yeo, Matthias H. Tschöp, Sabrina Diano, Jens C. Brüning, Daniela Cota
Journal: Nature Metabolism (2021)
Association of Implementation of a Comprehensive Preconception-to-Pregnancy Management Plan With Pregnancy Outcomes Among Chinese Pregnant Women With Type 1 Diabetes: The CARNATION Study
Authors: Xueying Zheng, Daizhi Yang, Sihui Luo, Jinhua Yan, Xiaohui Guo, Huixia Yang, Wei Bao, Leif Groop, Anne Dornhorst, Jianping Weng, Xueying Zheng, Daizhi Yang, Sihui Luo, Jinhua Yan, Huixia Yang, Xiaohui Guo, Fang Liu, Xingwu Ran Xinhua Xiao, Dalong Zhu, Ji Hu, Zhiguang Zhou, Tao Yang, Jiajun Zhao, Qin Huang, Hongyu Kuang, Zhen Liang, Guijun Qin, Danqing Chen, Shandong Ye, Yan Wu, Jianmin Niu, Tianrong Pan, Qiu Zhang, Yunfeng Shen, Minxiang Lei, Yan Zhang, Bin Yao, Wei Bao, Leif Groop, Anne Dornhorst, Jianping Weng
Journal: Diabetes Care (2021)

OBJECTIVE To investigate the effect on pregnancy outcome of integrating a comprehensive management plan for patients with type 1 diabetes (T1D) into the World Health Organization universal maternal care infrastructure. RESEARCH DESIGN AND METHODS A comprehensive preconception-to-pregnancy management plan for women with T1D was implemented in 11 centers from 8 Chinese cities from 2015 to 2017. Sequential eligible pregnant women (n = 133 out of 137 initially enrolled) with T1D and singleton pregnancies attending these management centers formed the prospective cohort. The main outcome was severe adverse pregnancy outcome comprising maternal mortality, neonatal death, congenital malformations, miscarriage in the second trimester, and stillbirth. We compared pregnancy outcomes in this prospective cohort with two control groups with the same inclusion and exclusion criteria: a retrospective cohort (n = 153) of all eligible pregnant women with T1D attending the same management centers from 2012 to 2014 and a comparison cohort (n = 116) of all eligible pregnant women with T1D receiving routine care from 2015 to 2017 in 11 different centers from 7 cities. RESULTS The rate of severe adverse pregnancy outcome was lower in the prospective cohort (6.02%) than in either the retrospective cohort (18.30%; adjusted odds ratio [aOR] 0.31 [95% CI 0.13–0.74]) or the contemporaneous comparison cohort (25.00%; aOR 0.22 [95% CI 0.09–0.52]). CONCLUSIONS The substantial improvements in the prospective cohort are evidence of a potentially clinically important effect of the comprehensive management plan on pregnancy outcomes among Chinese pregnant women with pregestational T1D. This supports the development of similar approaches in other countries.
In vitro biomimetic models for glioblastoma-a promising tool for drug response studies
Authors: Tijana Stanković, Teodora Ranđelović, Miodrag Dragoj, Sonja Stojković Burić, Luis Fernández, Ignacio Ochoa, Victor M. Pérez-García, Milica Pešić
Journal: Drug Resistance Updates (2021)

The poor response of glioblastoma to current treatment protocols is a consequence of its intrinsic drug resistance. Resistance to chemotherapy is primarily associated with considerable cellular heterogeneity, and plasticity of glioblastoma cells, alterations in gene expression, presence of specific tumor microenvironment conditions and blood-brain barrier. In an attempt to successfully overcome chemoresistance and better understand the biological behavior of glioblastoma, numerous tri-dimensional (3D) biomimetic models were developed in the past decade. These novel advanced models are able to better recapitulate the spatial organization of glioblastoma in a real time, therefore providing more realistic and reliable evidence to the response of glioblastoma to therapy. Moreover, these models enable the fine-tuning of different tumor microenvironment conditions and facilitate studies on the effects of the tumor microenvironment on glioblastoma chemoresistance. This review outlines current knowledge on the essence of glioblastoma chemoresistance and describes the progress achieved by 3D biomimetic models. Moreover, comprehensive literature assessment regarding the influence of 3D culturing and microenvironment mimicking on glioblastoma gene expression and biological behavior is also provided. The contribution of the blood-brain barrier as well as the blood-tumor barrier to glioblastoma chemoresistance is also reviewed from the perspective of 3D biomimetic models. Finally, the role of mathematical models in predicting 3D glioblastoma behavior and drug response is elaborated. In the future, technological innovations along with mathematical simulations should create reliable 3D biomimetic systems for glioblastoma research that should facilitate the identification and possibly application in preclinical drug testing and precision medicine.
Reply: Fertility restoration in azoospermic cancer survivors from testicular VSELs that survive oncotherapy upon transplanting MSCs
Authors: Christine Wyns, Marc Kanbar
Journal: Human Reproduction Update (2021)

Reply: Fertility restoration in azoospermic cancer survivors from testicular VSELs that survive oncotherapy upon transplanting MSCs Christine Wyns, Christine Wyns Andrology lab, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, BelgiumDepartment of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium Correspondence address. Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium. E-mail: christine.wyns@uclouvain.behttps://orcid.org/0000-0002-6581-5003 https://orcid.org/0000-0002-6581-5003 Search for other works by this author on: Oxford Academic PubMed Google Scholar Marc Kanbar Marc Kanbar Andrology lab, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, BelgiumDepartment of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Reproduction Update, Volume 27, Issue 3, May-June 2021, Pages 621–622, https://doi.org/10.1093/humupd/dmab007 Published: 22 February 2021
Endovascular Balloon Treatment of a Failing Arteriovenous Fistula. A Case Report.
Authors: Emmanuel Edafe
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

BACKGROUND: Arterio-venous (AV) fistula is created for patients requiring renal replacement therapy (hemodialysis and hemofiltration). A failing A-V fistula requires urgent treatment to keep it patent. Understanding the simple tips and tricks will contribute to the quality of life for the patient with end-stage renal disease and reducing radiation dose to the operator. CASE SUMMARY: A 77 year old male with end-stage renal disease, hypertension and coronary artery disease. He has been on regular haemodialysis after A-V fistula (left forearm) was constructed in 2013. He presented with 2 weeks history of A-V fistula occlusion. Examination was essentially normal. Serum sodium=136mmol/l, potassium=5.5mmol/l urea=100mg/l, creatinine=3.5mg/dl. The Doppler scan showed 50 % stenosis just proximal to the anastomosis with calcification. Percutenous arteriography and venography was done with non-compliance balloon (3x12mm) up to 24 atm . The post procedure venography showed restoration of flow across the fistula. CONCLUSION: Endovascular treatment of a failing A-V fistula can be life saving. The simple tips and tricks of using the groin route, reducing the concentration of contrast and maneuver devices may contribute to safety and reduce radiation to the operator.
Abstract PS18-17: Mdm2 inhibition synergises with endocrine therapy or cdk4/6 inhibition for the treatment of estrogen receptor-positive breast cancer
Authors: Neil Portman, Heloisa Milioli, Sarah Alexandrou, Rhiannon Coulson, Aliza Yong, Kristine Fernandez, KeeMing Chia, Ensar Halilovic, Davendra Segara, Andrew Parker, Sue Haupt, Ygal Haupt, Wayne Tilley, Alex Swarbrick, Liz Caldon, Elgene Lim
Journal: Cancer Research (2021)

Abstract Background: Resistance to endocrine therapy is a major clinical challenge in the management of estrogen receptor (ER)-positive breast cancer. In this setting p53 is frequently wildtype and its activity may be suppressed via upregulation of its key regulator MDM2. This underlies our rationale to evaluate MDM2 inhibition as a therapeutic strategy in treatment resistant ER-positive breast cancer. Methods: We used the MDM2 inhibitor NVP-CGM097 to treat in vitro and in vivo models alone and in combination with fulvestrant or palbociclib. We perform cell viability, cell cycle, apoptosis and senescence assays to evaluate antitumor effects in p53 wildtype and p53 mutant ER positive cell lines (MCF-7, ZR75-1, T-47D) and MCF-7 lines resistant to endocrine therapy and to CDK4/6 inhibition. We further assess the drug effects in patient-derived xenograft (PDX) models of endocrine-sensitive and -resistant ER positive breast cancer. Results: We demonstrate that MDM2 inhibition results in cell cycle arrest and increased apoptosis in p53-wildtype in vitro and in vivo breast cancer models, leading to potent anti-tumour activity. We find that endocrine therapy or CDK4/6 inhibition synergises with MDM2 inhibition but does not further enhance apoptosis. Instead, combination treatments result in profound regulation of cell cycle-related transcriptional programmes, with synergy achieved through increased antagonism of cell cycle progression. Combination therapy pushes cell lines resistant to fulvestrant or palbociclib to become senescent and significantly reduces tumour growth in a fulvestrant resistant patient derived xenograft model. Conclusions: We conclude that MDM2 inhibitors in combination with ER degraders or CDK4/6 inhibitors represent a rational strategy for treating advanced, endocrine resistant ER-positive breast cancer, operating through synergistic activation of cell cycle co-regulatory programs. Citation Format: Neil Portman, Heloisa Milioli, Sarah Alexandrou, Rhiannon Coulson, Aliza Yong, Kristine Fernandez, KeeMing Chia, Ensar Halilovic, Davendra Segara, Andrew Parker, Sue Haupt, Ygal Haupt, Wayne Tilley, Alex Swarbrick, Liz Caldon, Elgene Lim. Mdm2 inhibition synergises with endocrine therapy or cdk4/6 inhibition for the treatment of estrogen receptor-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-17.
CD19 CAR-T expressing PD-1/CD28 chimeric switch receptor as a salvage therapy for DLBCL patients treated with different CD19-directed CAR T-cell therapies
Authors: Yun Liang, Hui Liu, Zheming Lu, Wen Lei, Chaoting Zhang, Ping Li, Aibin Liang, Ken H. Young, Wenbin Qian
Journal: Journal of Hematology & Oncology (2021)

Abstract CD19-targeted chimeric antigen receptor T (CAR T) cell therapy is a promising option to treat relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). However, the majority of CAR T-treated patients will eventually progress and require salvage treatment, for which there is no current standard. In this study, we analyzed data from 6 patients with R/R DLBCL who experienced progression following CD19-CAR T therapy, and then received CD19-specific CAR T cells that express a PD-1/CD28 chimeric switch-receptor (CD19-PD-1/CD28-CAR T) as salvage therapy at our institution. After the second infusion of CAR T cells, 3 of 6 patients achieved complete remissions and the duration of the response of responsive patients ranged from 8 to 25 months. One patient showed a stable disease. In contrast, 2/6 patients died on 60 days because of progression disease. Importantly, no severe neurologic toxicity or cytokine release syndrome was observed. These data suggest that CD19-PD-1/CD28-CAR-T cells, a novel anti-CD19 CAR-T cell therapy, elicit a potent and durable anticancer response, and can be used in the post-CD19-CAR T failure setting.
Cleansing and separation procedures reflect resource concerns
Authors: Simone Schnall, Robert K. Henderson
Journal: Behavioral and Brain Sciences (2021)

Abstract We propose that procedures of separation have two functions, namely first, to establish the integrity of individual parts, and second, to make previously joint entities discreet and therefore countable. This allows taking stock of available resources, including evaluating the use of individual objects, a process that is especially adaptive under conditions of threat of contagious disease and resource scarcity.
Biallelic variants in COPB1 cause a novel, severe intellectual disability syndrome with cataracts and variable microcephaly
Authors: William L. Macken, Annie Godwin, Gabrielle Wheway, Karen Stals, Liliya Nazlamova, Sian Ellard, Ahmed Alfares, Taghrid Aloraini, Lamia AlSubaie, Majid Alfadhel, Sulaiman Alajaji, Htoo A. Wai, Jay Self, Andrew G. L. Douglas, Alexander P. Kao, Matthew Guille, Diana Baralle
Journal: Genome Medicine (2021)

Abstract Background Coat protein complex 1 (COPI) is integral in the sorting and retrograde trafficking of proteins and lipids from the Golgi apparatus to the endoplasmic reticulum (ER). In recent years, coat proteins have been implicated in human diseases known collectively as “coatopathies”. Methods Whole exome or genome sequencing of two families with a neuro-developmental syndrome, variable microcephaly and cataracts revealed biallelic variants in COPB1 , which encodes the beta-subunit of COPI (β-COP). To investigate Family 1’s splice donor site variant, we undertook patient blood RNA studies and CRISPR/Cas9 modelling of this variant in a homologous region of the Xenopus tropicalis genome. To investigate Family 2’s missense variant, we studied cellular phenotypes of human retinal epithelium and embryonic kidney cell lines transfected with a COPB1 expression vector into which we had introduced Family 2’s mutation. Results We present a new recessive coatopathy typified by severe developmental delay and cataracts and variable microcephaly. A homozygous splice donor site variant in Family 1 results in two aberrant transcripts, one of which causes skipping of exon 8 in COPB1 pre-mRNA, and a 36 amino acid in-frame deletion, resulting in the loss of a motif at a small interaction interface between β-COP and β’-COP. Xenopus tropicalis animals with a homologous mutation, introduced by CRISPR/Cas9 genome editing, recapitulate features of the human syndrome including microcephaly and cataracts. In vitro modelling of the COPB1 c.1651T&gt;G p.Phe551Val variant in Family 2 identifies defective Golgi to ER recycling of this mutant β-COP, with the mutant protein being retarded in the Golgi. Conclusions This adds to the growing body of evidence that COPI subunits are essential in brain development and human health and underlines the utility of exome and genome sequencing coupled with Xenopus tropicalis CRISPR/Cas modelling for the identification and characterisation of novel rare disease genes.
Abstract PS15-03: Breast complications in patients who received intraoperative radiation therapy compared to other forms of radiation therapy following breast conserving surgery
Authors: James Wheeler, Houman Vaghefi, Laura Morris, Fang Liu, Irina Sparks, Fiona Denham, Leonard Henry, Ashley Hardy, Meghan Schrock, Vanessa DePue, Leon Coody
Journal: Cancer Research (2021)

Abstract Introduction: Intraoperative radiation therapy (IORT) is a convenient treatment option for appropriate women with early stage breast cancer. Some patients undergoing IORT also need adjuvant whole breast radiation therapy due to adverse final pathologic features. Although there are various reports of the complication rates with patients undergoing IORT, comparisons with patients undergoing other forms of radiation therapy such as whole breast or accelerated partial breast radiation are sparse. Methods: A total of 293 patients underwent breast conserving surgery at the study institution between January 2016 and December 2019 for either ductal carcinoma in situ (DCIS) or invasive breast cancer. Three patients had bilateral breast cancer and one patient had a local recurrence having refused adjuvant treatment following breast conserving surgery, for a total of 297 treated breasts. 124 received whole breast radiation therapy, 70 did not receive radiation therapy, 47 received IORT alone, 15 received IORT and whole breast radiation therapy, 30 received accelerated partial breast radiation using external beam radiation (APBI-EB), and 9 received Ir-192 based high dose rate accelerated partial breast radiation (APBI-HDR). One patient with bilateral breast cancer did not complete whole breast radiation therapy to either breast. Complications included cellulitis, wound drainage, symptomatic seroma, delayed wound healing, and wet desquamation. Interventions included observation, antibiotics, wound packing, debridement, fluid aspiration, hydrogel dressings, and wound vacuums. Results: For the entire group, the incidence of wound complications was 20%. The risk of complications was 27.4% for those undergoing IORT (with or without whole breast radiation) compared to 18.3% for those not receiving IORT, which was not statistically different at the 5% significance level. For those who received both IORT and whole breast radiation, however, the proportion having complication was 53.3% versus 18.4% in the other groups. The difference was significant with a p-value 0.0032. Conclusion: Patients who undergo both IORT and whole breast radiation have an increased risk for wound complications. Citation Format: James Wheeler, Houman Vaghefi, Laura Morris, Fang Liu, Irina Sparks, Fiona Denham, Leonard Henry, Ashley Hardy, Meghan Schrock, Vanessa DePue, Leon Coody. Breast complications in patients who received intraoperative radiation therapy compared to other forms of radiation therapy following breast conserving surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-03.
Letter to the editor regarding: Multicentre, prospective, randomised study comparing the diagnostic yield of colon capsule endoscopy versus CT colonography in a screening population (the TOPAZ study)
Authors: Firas Ahmed, Cecelia Brewington, Kevin Jeffrey Chang, Courtney Coursey Moreno, Marc Gollub, Judy Yee
Journal: Gut (2021)

In a prospective, multicentre, randomised controlled trial in an average colon cancer risk population, the TOPAZ trial, Dr Cash and colleagues1 report that colon capsule endoscopy (CCE) revealed higher diagnostic yield (defined by finding a colonic polyp ≥6 mm that warrants an optical colonoscopy) and higher sensitivity compared with CT colonography (CTC). Based on these findings, Cash et al 1 advocate the use of CCE as a more accurate/superior diagnostic test among patients who cannot/prefer not to undergo optical colonoscopy. As abdominal radiologists experienced in CTC and as members of the American College of Radiology’s Colon Cancer Committee, we appreciate the effort by the authors in this clinical trial, but we have comments and concerns about the results, discussion and drawn conclusions: