tbuckley/cabot-search huggingface dataset:
Abstract 2051: Inhibiting CDC7 kinase for the treatment of Ewing sarcoma
Authors: Jeffrey C. Martin
Journal: Cancer Research (2021)

Abstract Ewing Sarcoma is a malignant tumor of the bone and soft tissue that is primarily driven by the fusion protein EWS-FLI1. With no current targeted therapy, treatment options remain limited and toxic. Recent reports have shown that Ewing tumors harbor large amounts of transcription-associated replication stress and that this offers an attractive therapeutic intervention point. Our group has shown that inhibition of the kinase complex DDK (CDC7-DBF4) results in apoptosis and a significant reduction in cell viability in EWS-FLI1-harboring Ewing's sarcoma cell lines. Also, low dose DDK inhibition in Ewing's sarcoma cells caused an S/G2 cell cycle accumulation at 24 hours, followed by re-entry into G1 and appearance of sub-G1 DNA. This suggests a failure to properly progress through S-phase followed by premature mitotic entry and mitotic catastrophe resulting in cell death. To this end, there was a significant increase in the formation of micronuclei and other aberrant mitotic structures upon DDK inhibition in Ewing's cells. Interestingly, there was minimal signs of mitotic accumulation, despite clear evidence of mitotic stress, indicating a failure to properly enforce a G2-M checkpoint. Importantly, these phenotypes were not mimicked with the use of the CDK2 inhibitor Roscotivine, suggesting an origin firing-independent basis for the sensitivity to DDK inhibition. Furthermore, we show that DDK inhibition synergizes with the TOP1 inhibitor Camptothecin and with the PARP1 inhibitor Talazoparib to kill Ewing Sarcoma cells in vitro. We have hypothesized this to be due to DDK's potential role in replication fork instability/restart. Together, these results suggest that Ewing sarcoma cells rely on the activity of DDK to maintain cell viability independently from its role in the regulation of replication origin initiation and suggest that DDK inhibition may prove to be a viable treatment option for patients with Ewing's sarcoma. Citation Format: Jeffrey C. Martin. Inhibiting CDC7 kinase for the treatment of Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2051.
Transperineal laser ablation for benign prostatic hyperplasia: Ejaculation sparing technique
Authors: A. Ruffo, F. Trama, E. Illiano, F. Iacono, N. Stanojevic, F. Zanfardino, G. Romeo, F. Riccardo, E. Costantini, R. Regine
Journal: European Urology (2021)
Extracellular matrix requirements for gastrointestinal organoid cultures
Authors: S. Rezakhani, N. Gjorevski, M.P. Lutolf
Journal: Biomaterials (2021)

Organoids are a new class of biological model systems that have garnered significant interest in the life sciences. When provided with the proper 3D matrix and biochemical factors, stem cells can self-organize and form tissue-specific organoids. Thus far, there has been a substantial effort to identify soluble niche components essential for organoid culture; however, the role of the solid extracellular matrix (ECM) as an essential element of the niche is still largely lacking. In this review, we discuss the importance of the ECM in intestinal, hepatic, and pancreatic organoid culture and how biomaterial-based approaches can be used to probe different ECM properties required for more physiologically and translationally relevant organoid models.
Health-Related Quality of Life, Depression, and Self-esteem in Patients With Androgenetic Alopecia
Authors: Chun-Hsien Huang, Yun Fu, Ching-Chi Chi
Journal: JAMA Dermatology (2021)

Androgenetic alopecia (AGA) is associated with trichodynia, anxiety, low self-esteem, and depression, which have implications for quality of life. However, no systematic evaluation has been performed on the association of AGA with health-related quality of life (HRQOL).To systematically examine the association of AGA with HRQOL and psychiatric disorders.Cochrane Library, PubMed, Embase, and WanFang databases were searched from inception through January 24, 2021.Case series, case-control studies, cross-sectional studies, cohort studies, and randomized clinical trials that examined either HRQOL or psychiatric disorders in patients with AGA were included. Studies published in languages other than English and Mandarin were excluded.The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used. The risk of bias in included studies was assessed with the Risk of Bias in Non-randomized Studies of Intervention (ROBINS-I) tool. A random-effects model meta-analysis was performed to calculate the pooled effect on HRQOL. A subgroup analysis according to sex and geographic regions was also conducted.The outcome was HRQOL of patients with AGA.A total of 41 studies involving 7995 patients was included. The pooled Dermatology Life Quality Index score was 8.16 (95% CI, 5.62-10.71). The pooled Hair-Specific Skindex-29 score indicated moderate impairment of emotions, with the meta-analysis showing a score of 29.22 (95% CI, 24.17-34.28) in the emotion dimension. The pooled Center for Epidemiologic Studies Depression Scale score did not indicate depression, with the meta-analysis showing a score of 14.98 (95% CI, 14.28-15.68). Factors that had a direct association with HRQOL included married or coupled status and receipt of medical treatments, whereas factors that had an inverse association with HRQOL included higher self-rated hair loss severity, lower visual analog scale score, and higher educational level.This systematic review and meta-analysis found a significant association of AGA with moderate impairment of HRQOL and emotions, but no association was found with depressive symptoms. The findings suggest that patients with AGA may need psychological and psychosocial support.
Abstract 17815: The Effects of Nanoparticle-mediated PPARγ Agonist Delivery on Plaque Stabilization: A Multichannel High-resolution Intravital Imaging Analysis
Authors: Jah Yeon Choi, Jiheun Ryu, Joon Woo Song, Ji Bak Kim, Dong Joo Oh, DaeGab Gweon, Hongki Yoo, Kyeongsoon Park, Jin Won Kim
Journal: Circulation (2015)

Introduction: Plaque inflammation is associated with fibrous cap destabilization and rupture. Hypothesis: We hypothesized that the specific delivery of a novel PPARγ agonist, lobeglitazone, to inflamed plaques via nanoparticle (NP) targeting mannose receptors on macrophages could reduce inflammation in atheromata and thus, tested it using serial optical intravital molecular imaging. Methods and Results: A novel near-infrared fluorescence (NIRF) probe was fabricated by chemically conjugating thiolated glycol chitosan with mannose-PEG, and NIRF dye Cy5.5 (ext/emi 675/694 nm) for imaging. Lobeglitazone was incorporated into NIRF-NP targeting macrophage mannose receptors (MMR). In vitro, MMR-NIRF-NP was selectively uptaken by RAW264.7 cells, and NIRF signals were estimated to be 10-fold over control group (p&lt;0.01). In ELISA and immunoblot analysis, lobeglitazone-incorporated MMR-NIRF-NP significantly decreased inflammatory cytokines. To assess the therapeutic effects in vivo, macrophage activity in the carotid plaques of apoE-/- mice were serially imaged using a customized multichannel intravital fluorescence microscope (IVFM) under mechanical carotid stabilization. After baseline imaging, lobeglitazone-loaded MMR-NIRF-NPs were intravenously injected (7 mg/kg, twice weekly) and plaque NIRF signals were compared with p.o. treated group and controls. Four weeks later, IVFM at the same plaques revealed that macrophage signals much more decreased in lobeglitazone-loaded NP treated mice compared to those at baseline, and controls (P&lt;0.05). FM and immunostainings corroborated the in vivo findings. Conclusions: Lobeglitazone-incorporated MMR-NIRF-NP was able to selectively target and image atheroma macrophages, and effectively reduce plaque inflammation as assessed by intravital optical imaging. NP-mediated lobeglitazone delivery could be a promising therapeutic strategy for high-risk plaque stabilization.
How to formulate appropriate review questions for systematic reviews in sports medicine and rehabilitation?
Authors: Mohammadreza Pourahmadi, Somayeh Delavari, Bart Koes, Abbasali Keshtkar, Maryam Nazemipour, Mohammad Ali Mansournia
Journal: British Journal of Sports Medicine (2021)

The practise of evidence-based medicine is a process of lifelong learning that requires up-to-date and insightful syntheses of existing evidence. Systematic reviews and meta-analyses are an effective method for consolidating high-volume, rapidly accruing and often conflicting scientific studies on a specific topic. Systematic reviews are crucial for the avoidance of research waste, by ensuring that new primary research is performed with full knowledge of what has already been conducted, and that new research evidence is interpreted in light of what is already known.1 Systematic reviews have become an invaluable resource in the sports medicine and rehabilitation literature that generates high-quality evidence and enhance clinical decision-making.

A successful systematic review project depends on how well the authors formulate the research question based on their preliminary search and/or their clinical interest. Each systematic review type needs a specific review question format to help authors focus specifically on elements related to their study. The current proliferation of review types is creating challenges to the terminology for describing such reviews.2 Hence, this paper aims to summarise and propose several formats to generate appropriate review questions in the field of sports medicine and rehabilitation research.

Systematic review methodology was pioneered in health sciences in the 1980s, and the number of systematic reviews published each year has exponentially increased since 1990. A preliminary search in the PubMed database showed that annual publications of systematic reviews in …
初期の小児期の発達プログラムのバングラデシュのプライマリヘルスケアサービスへの統合:オープンラベル,クラスタ無作為化対照試験【JST・京大機械翻訳】
Authors: Hamadani Jena D, Mehrin Syeda F, Tofail Fahmida, Hasan Mohammad I, Huda Syed N, Baker-Henningham Helen, Ridout Deborah, Grantham-McGregor Sally
Journal: The Lancet Global Health (2019)
Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma
Authors: Adi Diab, Scott S. Tykodi, Gregory A. Daniels, Michele Maio, Brendan D. Curti, Karl D. Lewis, Sekwon Jang, Ewa Kalinka, Igor Puzanov, Alexander I. Spira, Daniel C. Cho, Shanhong Guan, Erika Puente, Tuan Nguyen, Ute Hoch, Sue L. Currie, Wei Lin, Mary A. Tagliaferri, Jonathan Zalevsky, Mario Sznol, Michael E. Hurwitz
Journal: Journal of Clinical Oncology (2021)

Therapies that produce deep and durable responses in patients with metastatic melanoma are needed. This phase II cohort from the international, single-arm PIVOT-02 study evaluated the CD122-preferential interleukin-2 pathway agonist bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) in first-line metastatic melanoma.A total of 41 previously untreated patients with stage III/IV melanoma received BEMPEG 0.006 mg/kg plus NIVO 360 mg once every 3 weeks for ≤ 2 years; 38 were efficacy-evaluable (≥ 1 postbaseline scan). Primary end points were safety and objective response rate (blinded independent central review); other end points included progression-free survival, overall survival (OS), and exploratory biomarkers.At 29.0 months' median follow-up, the objective response rate was 52.6% (20 of 38 patients), and the complete response rate was 34.2% (13 of 38 patients). Median change in size of target lesions from baseline was -78.5% (response-evaluable population); 47.4% (18 of 38 patients) experienced complete clearance of target lesions. Median progression-free survival was 30.9 months (95% CI, 5.3 to not estimable). Median OS was not reached; the 24-month OS rate was 77.0% (95% CI, 60.4 to 87.3). Grade 3 and 4 treatment-related and immune-mediated adverse events occurred in 17.1% (7 of 41) and 4.9% (2 of 41) of patients, respectively. Increased polyfunctional responses in CD8+ and CD4+ T cells were seen in blood after treatment, driven by cytokines with effector functions. Early on-treatment blood biomarkers (CD8+ polyfunctional strength difference and eosinophils) correlated with treatment response.BEMPEG in combination with NIVO was tolerated, with relatively low rates of grade 3 and 4 treatment-related and immune-mediated adverse events. The combination had encouraging antitumor activity in first-line metastatic melanoma, including an extended median progression-free survival. Exploratory analyses associated noninvasive, on-treatment biomarkers with response, before radiologic evidence was observed.
Noise Reduction in Cochlear Implant Signal Processing: A Review and Recent Developments
Authors: Fergal Henry, Martin Glavin, Edward Jones
Journal: IEEE Reviews in Biomedical Engineering (2021)

Cochlear implant technology successfully restores hearing function to patients with sensory impairment. Although cochlear implant users generally hear well in quiet, they still find noisy conditions very challenging, hence the need to employ noise reduction algorithms in these systems to enhance the user experience <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">.</i> This paper reviews noise reduction algorithms in cochlear implants. Traditionally, such algorithms have been classified as either single- or multiple-channel, depending on the number of microphones they use. This review retains this general classification in looking at recent papers and extends it to reflect recent interest in machine learning techniques. The review concludes with consideration of promising future areas of research.
Abstract 817: Probing the diabetes - colorectal cancer link using gene - environment interaction analyses
Authors: Niki Dimou, Andre E. Kim, Orlagh Flanagan, Neil Murphy, Emmanouil Bouras, Peter T. Campbell, Graham Casey, Steven Gallinger, Stephen B. Gruber, Li Hsu, Mark A. Jenkins, Yi Lin, Victor Moreno, Conghui Qu, Edward Ruiz-Narvaez, Mariana C. Stern, Yu Tian, Kostas Tsilidis, W. James Gauderman, Marc J. Gunter, Ulrike Peters
Journal: Cancer Research (2021)

Abstract Background: Type 2 diabetes mellitus (T2D) is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship are unclear and it is not known if the association is modified by genetic variants. To provide insights into the molecular pathways potentially linking diabetes and colorectal cancer, we undertook a large-scale gene-environment interaction analysis (GxE). Methods: We tested multiplicative statistical interactions between approximately 7 million common (allele frequency &amp;gt;1%) genetic variants and T2D status in 31,529 colorectal cancer cases and 42,861 controls of European ancestry from 3 genetic consortia (GECCO/CCFR/CORECT). Statistical methods included traditional case-control logistic regression, case-only analyses, joint tests (2df/3df), and two-step approaches. We also explored additive and multiplicative interactions between polygenic risk score (PRS) of the known genome-wide significant loci for colorectal cancer and T2D. Results: Overall, T2D was positively associated with colorectal cancer risk [odds ratio [OR]: 1.25 (95% confidence interval [CI]: 1.14-1.36)]. A statistically significant interaction was identified between T2D status and an intronic variant in LRCH1 (rs9526201) and colorectal cancer risk using the 2-d.f. joint test (p-value:1.44x10-8). A statistically significant additive scale interaction between PRS for colorectal cancer and T2D was found (p-value: 1.8x10-10) such that the observed risk of developing colorectal cancer for individuals with T2D and a 1 standard deviation (SD) higher increment of PRS compared to non-diabetics with the lowest PRS was 0.184 more than if there was no interaction between T2D and PRS. Conclusion: These results suggest that variation in a gene related to immune function may modify the association of T2D with colorectal cancer and potentially provide novel insights into the biology underlying this relationship. Furthermore, our data show that genetic risk prediction models for CRC may need to consider non-genetic risk factors. Citation Format: Niki Dimou, Andre E. Kim, Orlagh Flanagan, Neil Murphy, Emmanouil Bouras, Peter T. Campbell, Graham Casey, Steven Gallinger, Stephen B. Gruber, Li Hsu, Mark A. Jenkins, Yi Lin, Victor Moreno, Conghui Qu, Edward Ruiz-Narvaez, Mariana C. Stern, Yu Tian, Kostas Tsilidis, W. James Gauderman, Marc J. Gunter, Ulrike Peters. Probing the diabetes - colorectal cancer link using gene - environment interaction analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 817.
An Extended Admixture Pulse Model Reveals the Limitations to Human–Neandertal Introgression Dating
Authors: Leonardo N M Iasi, Harald Ringbauer, Benjamin M Peter
Journal: Molecular Biology and Evolution (2021)

Neandertal DNA makes up 2-3% of the genomes of all non-African individuals. The patterns of Neandertal ancestry in modern humans have been used to estimate that this is the result of gene flow that occurred during the expansion of modern humans into Eurasia, but the precise dates of this event remain largely unknown. Here, we introduce an extended admixture pulse model that allows joint estimation of the timing and duration of gene flow. This model leads to simple expressions for both the admixture segment distribution and the decay curve of ancestry linkage disequilibrium, and we show that these two statistics are closely related. In simulations, we find that estimates of the mean time of admixture are largely robust to details in gene flow models, but that the duration of the gene flow can only be recovered if gene flow is very recent and the exact recombination map is known. These results imply that gene flow from Neandertals into modern humans could have happened over hundreds of generations. Ancient genomes from the time around the admixture event are thus likely required to resolve the question when, where, and for how long humans and Neandertals interacted.
Abstract 9864: Trends and Outcomes of Acute Stroke During Pregnancy and Puerperium in the United States
Authors: Islam Y Elgendy, Mohamed Gad, Ahmed Mahmoud, Ellen Keeley, Carl Pepine
Journal: Circulation (2019)

Background: Acute stroke with pregnancy or puerperium is devastating for mother and her family, yet data regarding incidence and contemporary trends are limited. Accordingly, we investigated the in...
Abstract 1825: SAR443216, a novel trispecific T cell engager with potent T cell-dependent cytotoxicity for HER2-low tumors
Authors: Wenwen Sha, Sri Vadde, Zhili Song, Edward Seung, Zhen Xing, Liqing Chen, Virna Cortez-Retamozo, Sukhvinder Sidhu, Dinesh Bangari, Lan Wu, Ronnie Wei, Zhi-yong Yang, Gary Nabel, Vasiliki Pelekanou, Michele Sanicola-Nadel, Serena Masciari, Dmitri Wiederschain, Lily Pao
Journal: Cancer Research (2021)

Abstract Current HER2-targeted therapies have markedly improved the outcome of cancer patients with HER2 overexpressing tumors. However, these patients may eventually relapse or develop treatment resistance. In addition, HER2-low patients that are not eligible for treatment constitute a significant portion of the breast cancer patients. To address these unmet needs, we have developed a novel HER2-targeting T cell engager, SAR443216. This is a trispecific antibody with binding sites for HER2, CD3 and CD28, and containing a mutated IgG4-Fc which lacks effector functions. CD28 binding contributes to T cell activation, including activation of IL-2 and NFκB pathways, as well as induction of anti-apoptotic protein, Bcl-xL. In the presence of HER2-positive cancer cells, SAR443216 is able to activate primary human CD4 and CD8 T cells, resulting in T cell proliferation and secretion of cytokines and granzyme B. Moreover, it has potent in vitro T cell-dependent cellular cytotoxicity (TDCC) against a panel of HER2-expressing cancer cell lines, including those that are HER2-low. The potency of in vitro TDCC is largely correlated with HER2 surface expression in the target cells. Finally, in a HER2-low breast cancer xenograft model, SAR443216 also exhibited significant anti-tumor activity in immuno-deficient NSG mice reconstituted with primary human T cells. Thus, SAR443216 represents a promising new drug for cancer patients with HER2-expressing tumors, including those who are currently ineligible for stand-of-care therapy. Citation Format: Wenwen Sha, Sri Vadde, Zhili Song, Edward Seung, Zhen Xing, Liqing Chen, Virna Cortez-Retamozo, Sukhvinder Sidhu, Dinesh Bangari, Lan Wu, Ronnie Wei, Zhi-yong Yang, Gary Nabel, Vasiliki Pelekanou, Michele Sanicola-Nadel, Serena Masciari, Dmitri Wiederschain, Lily Pao. SAR443216, a novel trispecific T cell engager with potent T cell-dependent cytotoxicity for HER2-low tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1825.