tbuckley/cabot-search huggingface dataset:
Targeting an Inducible SALL4-Mediated Cancer Vulnerability with Sequential Therapy
Authors: Junyu Yang, Chong Gao, Miao Liu, Yao-Chung Liu, Junsu Kwon, Jun Qi, Xi Tian, Alicia Stein, Yanjing V. Liu, Nikki R. Kong, Yue Wu, Shenyi Yin, Jianzhong Xi, Zhiyuan Chen, Kalpana Kumari, Hannan Wong, Hongbo Luo, Leslie E. Silberstein, Julie A.I. Thoms, Ashwin Unnikrishnan, John E. Pimanda, Daniel G. Tenen, Li Chai
Journal: Cancer Research (2021)

Abstract Oncofetal protein SALL4 is critical for cancer cell survival. Targeting SALL4, however, is only applicable in a fraction of cancer patients who are positive for this gene. To overcome this limitation, we propose to induce a cancer vulnerability by engineering a partial dependency upon SALL4. Following exogenous expression of SALL4, SALL4-negative cancer cells became partially dependent on SALL4. Treatment of SALL4-negative cells with the FDA-approved hypomethylating agent 5-aza-2′-deoxycytidine (DAC) resulted in transient upregulation of SALL4. DAC pretreatment sensitized SALL4-negative cancer cells to entinostat, which negatively affected SALL4 expression through a microRNA, miRNA-205, both in culture and in vivo. Moreover, SALL4 was essential for the efficiency of sequential treatment of DAC and entinostat. Overall, this proof-of-concept study provides a framework whereby the targeting pathways such as SALL4-centered therapy can be expanded, sensitizing cancer cells to treatment by transient target induction and engineering a dependency. Significance: These findings provide a therapeutic approach for patients harboring no suitable target by induction of a SALL4-mediated vulnerability.
An Approach to the Primary and Secondary Prevention of Gastric Cancer in the United States
Authors: Robert J. Huang, Meira Epplein, Chisato Hamashima, Il Ju Choi, Eunjung Lee, Dennis Deapen, Yanghee Woo, Thuy Tran, Shailja C. Shah, John M. Inadomi, David A. Greenwald, Joo Ha Hwang
Journal: Clinical Gastroenterology and Hepatology (2021)
Contribution of epididymal epithelial cell functions to sperm epigenetic changes and the health of progeny
Authors: Hong Chen, Maíra Bianchi Rodrigues Alves, Clémence Belleannée
Journal: Human Reproduction Update (2021)

Abstract BACKGROUND Spermatozoa acquire their motility and fertilizing abilities during their maturation through the epididymis. This process is controlled by epididymal epithelial cells that possess features adapted to sense and respond to their surrounding environment and to communicate with spermatozoa. During the past decade, new intercellular communication processes have been discovered, including the secretion and transport of molecules from the epithelium to spermatozoa via extracellular vesicles (EVs), as well as sensing of the intraluminal milieu by cellular extensions. OBJECTIVE AND RATIONALE This review addresses recent findings regarding epididymal epithelial cell features and interactions between spermatozoa and the epididymal epithelium as well as epigenetic modifications undergone by spermatozoa during transit through the epididymal microenvironment. SEARCH METHODS A systematic search was conducted in Pubmed with the keyword ‘epididymis’. Results were filtered on original research articles published from 2009 to 2021 and written in the English language. One hundred fifteen original articles presenting recent advancements on the epididymis contribution to sperm maturation were selected. Some additional papers cited in the primary reference were also included. A special focus was given to higher mammalian species, particularly rodents, bovines and humans, that are the most studied in this field. OUTCOMES This review provides novel insights into the contribution of epididymal epithelium and EVs to post-testicular sperm maturation. First, new immune cell populations have been described in the epididymis, where they are proposed to play a role in protecting the environment surrounding sperm against infections or autoimmune responses. Second, novel epididymal cell extensions, including dendrites, axopodia and primary cilia, have been identified as sensors of the environment surrounding sperm. Third, new functions have been outlined for epididymal EVs, which modify the sperm epigenetic profile and participate in transgenerational epigenetic inheritance of paternal traits. WIDER IMPLICATIONS Although the majority of these findings result from studies in rodents, this fundamental research will ultimately improve our knowledge of human reproductive physiopathologies. Recent discoveries linking sperm epigenetic modifications with paternal environmental exposure and progeny outcome further stress the importance of advancing fundamental research on the epididymis. From this, new therapeutic options for infertile couples and better counseling strategies may arise to increase positive health outcomes in children conceived either naturally or with ART.
Narrow-spectrum antibiotics for community-acquired pneumonia in Dutch adults (CAP-PACT): a cross-sectional, stepped-wedge, cluster-randomised, non-inferiority, antimicrobial stewardship intervention trial
Authors: Valentijn A Schweitzer, Inger van Heijl, Wim G Boersma, Wouter Rozemeijer, Kees Verduin, Marco J Grootenboers, Sanjay U C Sankatsing, Akke K van der Bij, Winnie de Bruijn, Heidi S M Ammerlaan, Ilse Overdevest, J M Milena Roorda-van der Vegt, Elske M Engel-Dettmers, Florence E Ayuketah-Ekokobe, Michiel B Haeseker, J Wendelien Dorigo-Zetsma, Paul D van der Linden, C H Edwin Boel, Jan J Oosterheert, Cornelis H van Werkhoven, Marc J M Bonten
Journal: The Lancet Infectious Diseases (2021)
Understanding and Addressing Cancer Care Costs in the United States
Authors: Carolyn Y. Fang, Zachary A.K. Frosch
Journal: JAMA Network Open (2021)

Nicholas G. Zaorsky, MD, MS; Chachrit Khunsriraksakul, BS; Samantha L. Acri, MPH; Dajiang J. Liu, PhD; Djibril M. Ba, MPH, PhD; John L. Lin, BS; Guodong Liu, PhD; Joel E. Segel, PhD; Joseph J. Drabick, MD; Heath B. Mackley, MD, MBA; Douglas L. Leslie, PhD
1156P Exosomal lncRNA HOTTIP assessment for non-small cell lung cancer surveillance after curative-intent surgery
Authors: H. Bing, N. Viñolas, Y. He, J. Canals, T. Díaz, R.M. Marrades, L. Molins, D. Martinez, J. Moisés, M. Acosta, C. Cros, M. Monzo, A. Navarro
Journal: Annals of Oncology (2021)
The management of post-transplantation recurrence of hepatocellular carcinoma
Authors: Luckshi Rajendran, Tommy Ivanics, Marco PAW Claasen, Hala Muaddi, Gonzalo Sapisochin
Journal: Clinical and Molecular Hepatology (2021)

The annual incidence of hepatocellular carcinoma (HCC) continues to rise. Over the last two decades, liver transplantation (LT) has become the preferable treatment of HCC, when feasible and strict selection criteria are met. With the rise in HCC-related LT, compounded by downstaging techniques and expansion of transplant selection criteria, a parallel increase in number of post-transplantation HCC recurrence is expected. Additionally, in the context of an immunosuppressed transplant host, recurrences may behave aggressively and more challenging to manage, resulting in poor prognosis. Despite this, no consensus or best practice guidelines for post-transplantation cancer surveillance and recurrence management for HCC currently exist. Studies with adequate population sizes and high-level evidence are lacking, and the role of systemic and locoregional therapies for graft and extrahepatic recurrences remains under debate. This review seeks to summarize the existing literature on post-transplant HCC surveillance and recurrence management. It highlights the value of early tumour detection, re-evaluating the immunosuppression regimen, and staging to differentiate disseminated recurrence from intrahepatic or extrahepatic oligo-recurrence. This ultimately guides decision-making and maximizes treatment effect. Treatment recommendations specific to recurrence type are provided based on currently available locoregional and systemic therapies.
Collaborate to stop antimicrobial resistance—for the sake of the planet
Authors: Priya Venkatesan
Journal: The Lancet Microbe (2021)

Antimicrobial resistance is one of the top ten global health threats facing us according to WHO, and threatens to undo more than 100 years of progress in medicine—currently, the UN estimates that around 700 000 people die annually from resistant infections. And the emergence and spread of resistance in all pathogen types is rising fast. For example, for Escherichia coli, resistance rates as high as 92·9% against ciprofloxacin and 36·0% against third-generation cephalosporins have been reported. Around 500 000 cases of rifampicin-resistant tuberculosis were identified in 2018, and more than 50% of infants in sub-Saharan Africa newly diagnosed with HIV have a virus that is resistant to non-nucleoside reverse-transcriptase inhibitors.
Extending treatment criteria for Barrett’s neoplasia: results of a nationwide cohort of 138 endoscopic submucosal dissection procedures
Authors: Sanne N. van Munster, Eva P. D. Verheij, Esther A. Nieuwenhuis, Johan G. J. A. Offerhaus, Sybren L. Meijer, Lodewijk A. A. Brosens, Bas L. A. M. Weusten, Alaa Alkhalaf, Ed B. E. Schenk, Erik J. Schoon, Wouter L. Curvers, Laurelle van Tilburg, Steffi E. M. van de Ven, Thjon J. Tang, Wouter B. Nagengast, Martin H. M. G. Houben, Kees C. A. Seldenrijk, Jacques J. G. H. M. Bergman, Arjun D. Koch, Roos E. Pouw
Journal: Endoscopy (2021)

The use of endoscopic submucosal dissection (ESD) is gradually expanding for treatment of neoplasia in Barrett's esophagus (BE). We aimed to report outcomes of all ESDs for BE neoplasia performed in the Netherlands.Retrospective assessment of outcomes, using treatment and follow-up data from a joint database.130/138 patients had complete ESDs, with 126/130 (97 %) en bloc resections. Median (interquartile range (IQR)) procedure time was 121 minutes (90-180). Pathology findings were high grade dysplasia (HGD) (5 %) or esophageal adenocarcinoma (EAC) T1a (43 %) or T1b (52 %; 19 % sm1, 33 % ≥ sm2). Among resections of HGD or T1a EAC lesions, 87 % (95 %CI 75 %-92 %) were both en bloc and R0; the corresponding value for T1b EAC lesions was 49 % (36 %-60 %). Among R1 resections, 10/34 (29 %) showed residual cancer, all detected at first endoscopic follow-up. The remaining 24 patients (71 %) showed no residual neoplasia. Six of these patients underwent surgery with no residual tumor; the remaining 18 underwent endoscopic follow-up during median 31 months with 1 local recurrence (annual recurrence rate 2 %). Among R0 resections, annual local recurrence rate during median 27 months was 0.5 %.In expert hands, ESD allows safe removal of bulky intraluminal neoplasia and submucosal cancer. ESD of the latter showed R1 resection margins in 50 %, yet only one third had persisting neoplasia at follow-up. To better stratify R1 patients with an indication for additional surgery, repeat endoscopy after healing of the ESD might be a helpful possible prognostic factor for residual cancer.
18P In vitro analysis of the combination of APR-246 and carboplatin in triple negative breast cancer (TNBC) and high grade serous ovarian cancer (HGSOC) cell lines and its impact on Aurora kinase A (AURKA)-p53 pathway
Authors: J.J. Martinez-Pretel, B. Pineda, K. Eguez, B. Ortega Morillo, J. Hochstadt, M. Monzon, A. Lluch-Hernandez, A. Cervantes, J.A. Perez Fidalgo
Journal: Annals of Oncology (2021)
Patient Health Outcomes following Dialysis Facility Closures in the United States
Authors: Jingbo Niu, Maryam K. Saeed, Wolfgang C. Winkelmayer, Kevin F. Erickson
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Although ongoing changes to reimbursement in United States dialysis care may increase the risk of dialysis facility closures, the effects of such closures on the health outcomes of patients are unknown. The authors examined the associations among dialysis facility closures and rates of hospitalizations and death. Patients affected by dialysis facility closures from January 2001 through April 2014 experienced rates of hospitalization that were 7%–9% higher compared with hospitalization rates of similar patients receiving care at facilities that did not close. Patients affected by closure also exhibited a higher rate of mortality compared with unaffected patients, although this difference was of borderline statistical significance. These findings highlight the need for effective policies that continue to mitigate risk of facility closures. Background Ongoing changes to reimbursement of United States dialysis care may increase the risk of dialysis facility closures. Closures may be particularly detrimental to the health of patients receiving dialysis, who are medically complex and clinically tenuous. Methods We used two separate analytic strategies—one using facility-based matching and the other using propensity score matching—to compare health outcomes of patients receiving in-center hemodialysis at United States facilities that closed with outcomes of similar patients who were unaffected. We used negative binomial and Cox regression models to estimate associations of facility closure with hospitalization and mortality in the subsequent 180 days. Results We identified 8386 patients affected by 521 facility closures from January 2001 through April 2014. In the facility-matched model, closures were associated with 9% higher rates of hospitalization (relative rate ratio [RR], 1.09; 95% confidence interval [95% CI], 1.03 to 1.16), yielding an absolute annual rate difference of 1.69 hospital days per patient-year (95% CI, 0.45 to 2.93). Similarly, in a propensity-matched model, closures were associated with 7% higher rates of hospitalization (RR, 1.07; 95% CI, 1.00 to 1.13; P =0.04), yielding an absolute rate difference of 1.08 hospital days per year (95% CI, 0.04 to 2.12). Closures were associated with nonsignificant increases in mortality (hazard ratio [HR], 1.08; 95% CI, 1.00 to 1.18; P= 0.05 for the facility-matched comparison; HR, 1.08; 95% CI, 0.99 to 1.17; P =0.08 for the propensity-matched comparison). Conclusions Patients affected by dialysis facility closures experienced increased rates of hospitalization in the subsequent 180 days and may be at increased risk of death. This highlights the need for effective policies that continue to mitigate risk of facility closures.
Emollients in infancy to prevent atopic dermatitis: A systematic review and meta‐analysis
Authors: Youjia Zhong, Miny Samuel, Hugo van Bever, Elizabeth Huiwen Tham
Journal: Allergy (2021)

Several studies have evaluated prophylactic emollients as a preventive strategy against atopic dermatitis (AD) and food allergy (FA). We aimed to synthesize the evidence on efficacy and safety of prophylactic emollients started during the first 6 weeks of infancy for prevention of AD and FA.MEDLINE, Embase, CINAHL, BIOSIS, and the Cochrane Library databases were searched systematically for randomized controlled trials published between January 2000 and July 2020, which assessed the effects of prophylactic emollients initiated within the first 6 weeks of life on the development of AD within 24 months of age, compared to no treatment. Risk of bias and certainty of evidence were assessed using the Cochrane Collaboration's tool and GRADE process, respectively.Of the 1486 articles identified, 10 studies fulfilled inclusion criteria. In infants given emollients, there was no significant reduction on the development of AD (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.64, 1.10) compared to the control group. However, there was significant benefit of prophylactic emollients (RR 0.75, 95% CI 0.62-1.11) in the high-risk population (n = 8 studies). There was also significant benefit (RR 0.59, 95% CI 0.43, 0.81) in studies (n = 6) where emollients were used continuously to the point of AD assessment; but not when treatment was ceased for an interval before AD assessment. There were no protective effects on FA found.The prophylactic application of emollients initiated in early infancy may prevent AD, especially in high-risk populations and when used continuously. We hypothesize that emollients may delay rather than prevent AD.
1227P Stereotactic body radiotherapy to the lung primary lesion improves the survival of patients with non-oligometastatic NSCLC harboring EGFR activating mutation with first-line EGFR-TKIs: A real-world study
Authors: H. Wei, X. Zhou, H. Yang, Y-L. Gong, J. Wang, Y. Xu, L. Zhou, J. Xue, B. Zou, Y. Zhang, J. Zhu, F. Peng, M. Huang, Y. Lu, Y. Liu
Journal: Annals of Oncology (2021)
Covid-19: Trial participants are offered approved vaccines so they can travel abroad
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: Trial participants are offered approved vaccines so they can travel abroad Elisabeth MahasePeople who took part in covid-19 vaccine trials in the UK will be offered two doses of an approved vaccine from next week to allow them to travel internationally, the government has said.EM is a participant in the Valneva covid-19 vaccine trial. 1
Music, bonding, and human evolution: A critique
Authors: Bjorn Merker
Journal: Behavioral and Brain Sciences (2021)

Abstract Savage et al. propose that music filled a hypothetical “bonding gap” in human sociality by Baldwinian gene-culture coevolution (or protracted cognitive niche construction). Both these stepping stones to an evolutionary account of the function and origin of music are problematic. They are scrutinized in this commentary, and an alternative is proposed.
Microvascular Resistance Reserve for Assessment of Coronary Microvascular Function
Authors: Bernard De Bruyne, Nico H.J. Pijls, Emanuele Gallinoro, Alessandro Candreva, Stephane Fournier, Danielle C.J. Keulards, Jeroen Sonck, Marcel van’t Veer, Emanuele Barbato, Jozef Bartunek, Marc Vanderheyden, Eric Wyffels, Annemiek De Vos, Mohamed El Farissi, Pim A.L. Tonino, Olivier Muller, Carlos Collet, William F. Fearon
Journal: Journal of the American College of Cardiology (2021)
The search for realistic evidence on the outcomes of obstructive sleep apnoea
Authors: Sophia Schiza, Patrick Lévy, Miguel Angel Martinez-Garcia, Jean-Louis Pepin, Anita Simonds, Winfried Randerath
Journal: European Respiratory Journal (2021)

<b>The reported effect of CPAP on cardiovascular outcomes in sleep apnoea should be interpreted with caution and several factors must be considered before definite conclusions can be drawn</b>https://bit.ly/3lLQG4d
Engineering a folic acid-decorated ultrasmall gemcitabine nanocarrier for breast cancer therapy: Dual targeting of tumor cells and tumor-associated macrophages
Authors: Pearl Moharil, Zhuoya Wan, Apurva Pardeshi, Jiang Li, Haozhe Huang, Zhangyi Luo, Sanjay Rathod, Ziqian Zhang, Yuang Chen, Bei Zhang, Christian A. Fernandez, Jingjing Sun, Song Li
Journal: Acta Pharmaceutica Sinica B (2021)

Combination of passive targeting with active targeting is a promising approach to improve the therapeutic efficacy of nanotherapy. However, most reported polymeric systems have sizes above 100 nm, which limits effective extravasation into tumors that are poorly vascularized and have dense stroma. This will, in turn, limit the overall effectiveness of the subsequent uptake by tumor cells via active targeting. In this study, we combined the passive targeting via ultra-small-sized gemcitabine (GEM)-based nanoparticles (NPs) with the active targeting provided by folic acid (FA) conjugation for enhanced dual targeted delivery to tumor cells and tumor-associated macrophages (TAMs). We developed an FA-modified prodrug carrier based on GEM (PGEM) to load doxorubicin (DOX), for co-delivery of GEM and DOX to tumors. The co-delivery system showed small particle size of ∼10 nm in diameter. The ligand-free and FA-targeted micelles showed comparable drug loading efficiency and a sustained DOX release profile. The FA-conjugated micelles effectively increased DOX uptake in cultured KB cancer cells that express a high level of folate receptor (FR), but no obvious increase was observed in 4T1.2 breast cancer cells that have a low-level expression of FR. Interestingly, in vivo, systemic delivery of FA-PGEM/DOX led to enhanced accumulation of the NPs in tumor and drastic reduction of tumor growth in a murine 4T1.2 breast cancer model. Mechanistic study showed that 4T1.2 tumor grown in mice expressed a significantly higher level of FOLR2, which was selectively expressed on TAMs. Thus, targeting of TAM may also contribute to the improved in vivo targeted delivery and therapeutic efficacy.
1313P Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) tumor expression in a phase I/II study of tusamitamab ravtansine (SAR408701) in patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: J-Y. Scoazec, A-L. Bauchet, J. Adam, P. Rochaix, G. MacGrogan, J.E. Kim, P. Nuciforo, F. López-Rios, D. Frisman, G. Cesarone, S. Bernstein, J. Lee, C. Henry, M-L. Ozoux, A-M. Lefebvre
Journal: Annals of Oncology (2021)
Mode of Obstetric Delivery in Kidney and Liver Transplant Recipients and Associated Maternal, Neonatal, and Graft Morbidity During 5 Decades of Clinical Practice
Authors: Ophelia Yin, Aneesh Kallapur, Lisa Coscia, Lorna Kwan, Megha Tandel, Serban Constantinescu, Michael J. Moritz, Yalda Afshar
Journal: JAMA Network Open (2021)

Rates of cesarean delivery (CD) are increased among transplant recipients. There is a need to define the indications for CD and associated outcomes among transplant recipients to determine the safest mode of obstetric delivery.
10P DS-6000a, a novel CDH6-targeting antibody-drug conjugate with a novel DNA topoisomerase I inhibitor DXd, demonstrates potent antitumor activity in preclinical models
Authors: H. Suzuki, S. Nagase, C. Saito, M. Nagata, Y. Kaneda, K. Honda, Y. Nishiya, T. Honda, T. Nakada, R. Goto, T. Ishizaka, Y. Myobatake, Y. Abe, T. Agatsuma
Journal: Annals of Oncology (2021)
Trainees removed from cardiac surgery unit following concerns about “interpersonal behaviours”
Authors: Abi Rimmer
Journal: BMJ (2021)

Five trainees have been removed from the adult cardiac surgical service at Newcastle’s Freeman Hospital following an invited review by the Royal College of Surgeons.

The BBC reported on 29 September that five junior doctors have been transferred out of the hospital, which is managed by Newcastle upon Tyne Hospitals NHS Foundation Trust.1 A spokesperson for the trust said that in April 2021 it invited the Royal College …
1711P Real-world study of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal tumors
Authors: N. Xu, H. Yan, C. Mao, Y. Chen, G. Zhang, G. Cheng, H. Jiang, J. Yan, M. Chen, N. Zhang, X. Wang, J. Zhang, X. Shen, G. Wang, W. Zheng, Z. Han, Z. Wang, L. Xu, L. Ding, R. Xu
Journal: Annals of Oncology (2021)
A SARS-CoV-2 nucleocapsid ELISA represents a low-cost alternative to lateral flow testing for community screening in LMI countries
Authors: Maria Victoria Humbert, Precious Chinonyerem Opurum, Nathan J Brendish, Stephen Poole, Peijun He, Ioannis Katis, Jerry Quaye, Yaw Bediako, Patrick Jacques Duriez, Robert W Eason, Collin Sones, Osbourne Quaye, Gordon A Awandare, Myron Christodoulides, Tristan W Clark, Peter K Quashie, Christopher J McCormick
Journal: Journal of Infection (2021)
LBA51 EMPOWER-Lung 3: Cemiplimab in combination with platinum doublet chemotherapy for first-line (1L) treatment of advanced non-small cell lung cancer (NSCLC)
Authors: M. Gogishvili, T. Melkadze, T. Makharadze, D. Giorgadze, M. Dvorkin, K.D. Penkov, K. Laktionov, G. Nemsadze, M. Nechaeva, I. Rozhkova, E. Kalinka, C. Gessner, B. Moreno-Jaime, R. Passalacqua, S. Li, K. McGuire, R.G.W. Quek, G. Gullo, P. Rietschel
Journal: Annals of Oncology (2021)
79P SETD2 a potential tissue-agnostic predictive biomarker for ICIs in solid tumors
Authors: Y. Chen, X. Zheng, J. Xiong, Y. Guan, Y. Li, X. Gao, J. Lin, Z. Fei, L. Chen, L. Chen, G. Chen, X. Yi, W. Cao, X. Ai, C. Zhou, X. Li, J. Zhao, X. Yan, Q. Yu, C. Chen
Journal: Annals of Oncology (2021)