tbuckley/cabot-search huggingface dataset:
Engineering sperm-binding IgG antibodies for the development of an effective nonhormonal female contraception
Authors: Bhawana Shrestha, Alison Schaefer, Yong Zhu, Jamal Saada, Timothy M. Jacobs, Elizabeth C. Chavez, Stuart S. Olmsted, Carlos A. Cruz-Teran, Gabriela Baldeon Vaca, Kathleen Vincent, Thomas R. Moench, Samuel K. Lai
Journal: Science Translational Medicine (2021)

Many women risk unintended pregnancy because of medical contraindications or dissatisfaction with contraceptive methods, including real and perceived side effects associated with the use of exogenous hormones. We pursued direct vaginal delivery of sperm-binding monoclonal antibodies (mAbs) that can limit progressive sperm motility in the female reproductive tract as a strategy for effective nonhormonal contraception. Here, motivated by the greater agglutination potencies of polyvalent immunoglobulins but the bioprocessing ease and stability of immunoglobulin G (IgG), we engineered a panel of sperm-binding IgGs with 6 to 10 antigen-binding fragments (Fabs), isolated from a healthy immune-infertile woman against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) were at least 10- to 16-fold more potent and faster at agglutinating sperm than the parent IgG while preserving the crystallizable fragment (Fc) of IgG that mediates trapping of individual spermatozoa in mucus. The increased potencies translated into effective (&gt;99.9%) reduction of progressively motile sperm in the sheep vagina using as little as 33 μg of the 10-Fab HM-IgG. HM-IgGs were produced at comparable yields and had identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for nonhormonal contraception but also a promising platform for engineering potent multivalent mAbs for other biomedical applications.
<i>Lacticaseibacillus paracasei</i> DG enhances the lactoferrin anti-SARS-CoV-2 response in Caco-2 cells
Authors: Claudio Salaris, Melania Scarpa, Marina Elli, Alice Bertolini, Simone Guglielmetti, Fabrizio Pregliasco, Paola Brun, Ignazio Castagliuolo
Journal: Gut Microbes (2021)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the ongoing global pandemic of coronavirus disease 2019 (COVID-19), which primarily manifests with respiratory distress and may also lead to symptoms associated with the gastrointestinal tract. Probiotics are living microorganisms that have been shown to confer immune benefits. In this study, we investigated the immunomodulatory effects and anti-SARS-CoV-2 activity of three different Lacticaseibacillus probiotic strains, either alone or in combination with lactoferrin, using the intestinal epithelial Caco-2 cell line. Our results revealed that the Lacticaseibacillus paracasei DG strain significantly induced the expression of genes involved in protective antiviral immunity and prevented the expression of proinflammatory genes triggered by SARS-CoV-2 infection. Moreover, L. paracasei DG significantly inhibited SARS-CoV-2 infection in vitro. L. paracasei DG also positively affected the antiviral immune activity of lactoferrin and significantly augmented its anti-SARS-CoV-2 activity in Caco-2 intestinal epithelial cells. Overall, our work shows that the probiotic strain L. paracasei DG is a promising candidate that exhibits prophylactic potential against SARS-CoV-2 infection.
Editor's Note: Dopamine Blocks Stress-mediated Ovarian Carcinoma Growth
Authors: Myrthala Moreno-Smith, Chunhua Lu, Mian M.K. Shahzad, Guillermo N. Armaiz Pena, Julie K. Allen, Rebecca L. Stone, Lingegowda S. Mangala, Hee Dong Han, Hye Sun Kim, Donna Farley, Gabriel Lopez Berestein, Steve W. Cole, Susan K. Lutgendorf, Anil K. Sood
Journal: Clinical Cancer Research (2021)

The editors are publishing this note to alert readers to concerns about [this article][1] ([1][2]). Four sets of identical representative images exist: Figure 2A Tunel-DR2/Ctrl and Fig. 2B Tunel-DR2/Ctrl siRNA; Fig. 2A CD31/Ctrl and Fig. 2B CD31/Ctr siRNA; Fig. 2A CD31/DA and Fig. 2B CD31/DA; and
Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft Tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer Trial
Authors: Anne-Sophie Defachelles, Emilie Bogart, Michela Casanova, Johannes H. M. Merks, Gianni Bisogno, Giuseppina Calareso, Soledad Gallego Melcon, Susanne Andrea Gatz, Marie-Cécile Le Deley, Kieran McHugh, Alicia Probst, Nathalie Rocourt, Rick R. van Rijn, Keith Wheatley, Véronique Minard-Colin, Julia C. Chisholm
Journal: Journal of Clinical Oncology (2021)

The VIT-0910 trial was conducted to evaluate efficacy and safety of the vincristine-irinotecan combination with and without temozolomide (VIT and VI, respectively) in relapsed or refractory rhabdomyosarcoma (RMS).In this randomized European phase II trial, patients age 0.5-50 years received 21-day cycles combining vincristine (1.5 mg/m2 once a day on day 1 and day 8) and irinotecan (50 mg/m2 once a day from day 1 to day 5) with and without temozolomide (125 mg/m2 once a day from day 1 to day 5 and 150 mg/m2 once a day from cycle 2), until progression or unacceptable toxicity. The primary end point was objective response rate after two cycles. Secondary end points included best response, progression-free survival, overall survival, and adverse events. A Simon 2-stage design was initially planned to separately analyze 40 patients/arm. After amendment, the trial sample size was increased to 120 and a comparison between arms, adjusted for confounding factors, was added to the statistical plan (ClinicalTrials.gov, NCT01355445).Overall, 120 patients (60 per arm) were recruited in 37 European centers. The median age was 11 years (range, 0.75-45); 89% of patients had a relapsed RMS. The objective response rate was 44% (24 of 55 evaluable patients) for VIT versus 31% (18 of 58) for VI (adjusted odds ratio, 0.50; 95% CI, 0.22 to 1.12; P = .09). The VIT arm achieved significantly better overall survival (adjusted hazard ratio, 0.55; 95% CI, 0.35 to 0.84; P = .006) compared with VI, with consistent progression-free survival results (adj-hazard ratio, 0.68; 95% CI, 0.46 to 1.01; P = .059). Overall, patients experienced adverse events ≥ grade 3 more frequently with VIT than VI (98% v 78%, respectively; P = .009), including a significant excess of hematologic toxicity (81% v 61%; P = .025).The addition of temozolomide to VI improved chemotherapy efficacy for patients with relapsed RMS, with manageable increase in toxicity. VIT is considered the new standard treatment in these patients in the European paediatric Soft Tissue Sarcoma Group and will be the control arm in the next randomized trial.
Coevolution between MHC Class I and Antigen-Processing Genes in Salamanders
Authors: Gemma Palomar, Katarzyna Dudek, Magdalena Migalska, J W Arntzen, G Francesco Ficetola, Dušan Jelić, Elizabeth Jockusch, Inigo Martínez-Solano, Masatoshi Matsunami, H Bradley Shaffer, Judit Vörös, Bruce Waldman, Ben Wielstra, Wiesław Babik
Journal: Molecular Biology and Evolution (2021)

Proteins encoded by antigen-processing genes (APGs) provide major histocompatibility complex (MHC) class I (MHC-I) with antigenic peptides. In mammals, polymorphic multigenic MHC-I family is served by monomorphic APGs, whereas in certain nonmammalian species both MHC-I and APGs are polymorphic and coevolve within stable haplotypes. Coevolution was suggested as an ancestral gnathostome feature, presumably enabling only a single highly expressed classical MHC-I gene. In this view coevolution, while optimizing some aspects of adaptive immunity, would also limit its flexibility by preventing the expansion of classical MHC-I into a multigene family. However, some nonmammalian taxa, such as salamanders, have multiple highly expressed MHC-I genes, suggesting either that coevolution is relaxed or that it does not prevent the establishment of multigene MHC-I. To distinguish between these two alternatives, we use salamanders (30 species from 16 genera representing six families) to test, within a comparative framework, a major prediction of the coevolution hypothesis: the positive correlation between MHC-I and APG diversity. We found that MHC-I diversity explained both within-individual and species-wide diversity of two APGs, TAP1 and TAP2, supporting their coevolution with MHC-I, whereas no consistent effect was detected for the other three APGs (PSMB8, PSMB9, and TAPBP). Our results imply that although coevolution occurs in salamanders, it does not preclude the expansion of the MHC-I gene family. Contrary to the previous suggestions, nonmammalian vertebrates thus may be able to accommodate diverse selection pressures with flexibility granted by rapid expansion or contraction of the MHC-I family, while retaining the benefits of coevolution between MHC-I and TAPs.
Editor's Note: The Clinical Relevance of Stromal Matrix Metalloproteinase Expression in Ovarian Cancer
Authors: Aparna A. Kamat, Mavis Fletcher, Lynn M. Gruman, Peter Mueller, Adriana Lopez, Charles N. Landen, Liz Han, David M. Gershenson, Anil K. Sood
Journal: Clinical Cancer Research (2021)

The editors are publishing this note to alert readers to a concern about [this article][1] ([1][2]): Fig. 1A and G appear similar. The authors would like to clarify that adjacent sections of the same patient sample were used. The authors stand by the conclusions in the article. 1. 1.[↵][3]1.
Abstract 14687: Activation of Sirt1 Suppresses Hypertrophic Response of Cardiomyocytes by Inhibition of H3K9 Acetylation via Proteasome-mediated p300 Degradation.
Authors: Atsushi Kuno, Masaya Tanno, Satoko Ishikawa, Yoshiyuki Horio, Tetsuji Miura
Journal: Circulation (2010)

Background: Histone acetylation promotes gene transcription and plays a role in cardiac hypertrophy. Although activation of the histone/protein deacetylase Sirt1 has been shown to afford cardiomyoc...
O-12 Phase II study of preoperative chemoradiotherapy plus avelumab in patients with locally advanced rectal cancer: The AVANA study
Authors: L. Salvatore, M. Bensi, S. Corallo, F. Bergamo, I. Pellegrini, C. Rasola, B. Borelli, E. Tamburini, G. Randon, S. Galuppo, A. Boccaccino, M. Viola, A. Auriemma, E. Fea, C. Barbara, B. Corvari, S. Bustreo, V. Smiroldo, B. Barbaro, G. Tortora
Journal: Annals of Oncology (2021)
Prevalence, Costs, and Consequences of Low-Value Preprocedural Urinalyses in the US
Authors: Erica S. Shenoy, Mia Amalia Giuriato, Zirui Song
Journal: JAMA Internal Medicine (2021)

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Helen Salisbury: Running on empty
Authors: Helen Salisbury
Journal: BMJ (2021)

Most years, there's a noticeable slackening in the pace of GPs' work over the summer.Even as colleagues disappear on holiday, their absence is more than balanced out by a reduction in patient demand.This is partly due to patients also going away, and partly down to seasonal infections being in abeyance.The word that seems to follow most naturally after "summer" is "holiday," and when the sun's shining and the days are long, it feels wrong to be stuck inside working-but it's a lot less painful when you can leave while it's still light.
Abstract 14276: Brazil Nut Consumption Improves Postprandial Satiety, Blood Glucose and Insulin Responses in Healthy Adults
Authors: Alison Rosenstock, Megan Connolly, Rebecca Weller, Mee Young Hong
Journal: Circulation (2018)

Introduction: Brazil nuts are the highest known food source of selenium. Selenium has exhibited a multitude of health benefits including increased antioxidant capacity, improvement of lipid profile...
Editor's Note: Targeting Src in Mucinous Ovarian Carcinoma
Authors: Koji Matsuo, Masato Nishimura, Justin N. Bottsford-Miller, Jie Huang, Kakajan Komurov, Guillermo N. Armaiz-Pena, Mian M.K. Shahzad, Rebecca L. Stone, Ju Won Roh, Angela M. Sanguino, Chunhua Lu, Dwight D. Im, Neil B. Rosenshien, Atsuko Sakakibara, Tadayoshi Nagano, Masato Yamasaki, Takayuki Enomoto, Tadashi Kimura, Prahlad T. Ram, Kathleen M. Schmeler, Gary E. Gallick, Kwong K. Wong, Michael Frumovitz, Anil K. Sood
Journal: Clinical Cancer Research (2021)

The editors are publishing this note to alert readers to a concern about [this article][1] ([1][2]): in Fig. 5B, the representative images for the Control and oxaliplatin + dasatinib panels of CD31 are from the same image file. The authors apologize for this error and stand by the conclusions in the
Advances in allergen‐specific immune cell measurements for improved detection of allergic sensitization and immunotherapy responses
Authors: Menno C. van Zelm, Craig I. McKenzie, Nirupama Varese, Jennifer M. Rolland, Robyn E. O’Hehir
Journal: Allergy (2021)

Abstract Over the past two decades, precision medicine has advanced diagnostics and treatment of allergic diseases. Component‐resolved analysis of allergen sensitization facilitates stratification of patients. Furthermore, new formulations of allergen immunotherapy (AIT) products can more effectively deliver the relevant components. Molecular insights from the identification of allergen component sensitization and clinical outcomes of treatment with new AIT formulations can now be utilized for a deeper understanding of the nature of the pathogenic immune response in allergy and how this can be corrected by AIT. Fundamental in these processes are the allergen‐specific B and T cells. Within the large B‐ and T‐cell compartments, only those that specifically recognize the allergen with their immunoglobulin (Ig) or T‐cell receptor (TCR), respectively, are of clinical relevance. With peripheral blood allergen‐specific B‐ and T‐cell frequencies below 1%, bulk cell analysis is typically insufficiently sensitive. We here review the latest technologies to detect allergen‐specific B and T cells, as well as new developments in utilizing these tools for diagnostics and therapy monitoring to advance precision medicine for allergic diseases.
Plasmonically Enhanced CRISPR/Cas13a‐Based Bioassay for Amplification‐Free Detection of Cancer‐Associated RNA
Authors: Lin Liu, Zheyu Wang, Yixuan Wang, Jingyi Luan, Jeremiah J. Morrissey, Rajesh R. Naik, Srikanth Singamaneni
Journal: Advanced Healthcare Materials (2021)

Novel methods that enable sensitive, accurate and rapid detection of RNA would not only benefit fundamental biological studies but also serve as diagnostic tools for various pathological conditions, including bacterial and viral infections and cancer. Although highly sensitive, existing methods for RNA detection involve long turn-around time and extensive capital equipment. Here, an ultrasensitive and amplification-free RNA quantification method is demonstrated by integrating CRISPR-Cas13a system with an ultrabright fluorescent nanolabel, plasmonic fluor. This plasmonically enhanced CRISPR-powered assay exhibits nearly 1000-fold lower limit-of-detection compared to conventional assay relying on enzymatic reporters. Using a xenograft tumor mouse model, it is demonstrated that this novel bioassay can be used for ultrasensitive and quantitative monitoring of cancer biomarker (lncRNA H19). The novel biodetection approach described here provides a rapid, ultrasensitive, and amplification-free strategy that can be broadly employed for detection of various RNA biomarkers, even in resource-limited settings.
Risk-benefit assessment of onlay and retrorectus mesh augmentation for incisional hernia prophylaxis: A secondary analysis from network meta-analysis
Authors: Amarit Tansawet, Pawin Numthavaj, Suphakarn Techapongsatorn, Gareth McKay, John Attia, Oraluck Pattanaprateep, Ammarin Thakkinstian
Journal: International Journal of Surgery (2021)
エキソヌクレアーゼ1によるMLH1欠損誘発DNA過剰切断はcGAS経路を活性化する【JST・京大機械翻訳】
Authors: Guan Junhong, Lu Changzheng, Jin Qihuang, Lu Huiming, Chen Xiang, Tian Lei, Zhang Yanbin, Ortega Janice, Zhang Junqiu, Siteni Silvia, Chen Mingyi, Gu Liya, W Shay Jerry, J Davis Anthony, J Chen Zhijian, Fu Yang-Xin, Li Guo-Min
Journal: Cancer Cell (2021)
Screening for Gestational Diabetes
Authors: Jill Jin
Journal: JAMA (2021)

US Preventive Services Task Force; Karina W. Davidson, PhD, MASc; Michael J. Barry, MD; Carol M. Mangione, MD, MSPH; Michael Cabana, MD, MA, MPH; Aaron B. Caughey, MD, PhD; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; Chyke A. Doubeni, MD, MPH; Martha Kubik, PhD, RN; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Lori Pbert, PhD; Michael Silverstein, MD, MPH; James Stevermer, MD, MSPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
Kinobead Profiling Reveals Reprogramming of BCR Signaling in Response to Therapy within Primary CLL Cells
Authors: Adam J. Linley, Laura I. Karydis, Anil K. Mondru, Annalisa D'Avola, Humood Al Shmrany, Silvia Cicconi, Rebecca Griffin, Francesco Forconi, Andrew R. Pettitt, Nagesh Kalakonda, Andrew C. Rawstron, Peter Hillmen, Andrew J. Steele, David J. MacEwan, Graham Packham, Ian A. Prior, Joseph R. Slupsky
Journal: Clinical Cancer Research (2021)

Abstract Purpose: B-cell receptor (BCR) signaling is critical for the pathogenesis of chronic lymphocytic leukemia (CLL), promoting both malignant cell survival and disease progression. Although vital, understanding of the wider signaling network associated with malignant BCR stimulation is poor. This is relevant with respect to potential changes in response to therapy, particularly involving kinase inhibitors. In the current study, we describe a novel high-resolution approach to investigate BCR signaling in primary CLL cells and track the influence of therapy on signaling response. Experimental Design: A kinobead/mass spectrometry–based protocol was used to study BCR signaling in primary CLL cells. Longitudinal analysis of samples donated by clinical trial patients was used to investigate the impact of chemoimmunotherapy and ibrutinib on signaling following surface IgM engagement. Complementary Nanostring and immunoblotting analysis was used to verify our findings. Results: Our protocol isolated a unique, patient-specific signature of over 30 kinases from BCR-stimulated CLL cells. This signature was associated with 13 distinct Kyoto Encyclopedia of Genes and Genomes pathways and showed significant change in cells from treatment-naïve patients compared with those from patients who had previously undergone therapy. This change was validated by longitudinal analysis of clinical trials samples where BCR-induced kinome responses in CLL cells altered between baseline and disease progression in patients failing chemoimmunotherapy and between baseline and treatment in patients taking ibrutinib. Conclusions: These data comprise the first comprehensive proteomic investigation of the BCR signaling response within CLL cells and reveal unique evidence that these cells undergo adaptive reprogramming of this signaling in response to therapy.
SO-4 Progression-free survival in patients with cholangiocarcinoma with FGFR2 fusions or rearrangements: A FIGHT-202 post-hoc analysis of prior systemic therapy response
Authors: G. Abou-Alfa, V. Sahai, A. Hollebecque, G. Vaccaro, D. Melisi, R. Al-Rajabi, A. Paulson, M. Borad, D. Gallinson, A. Murphy, D. Oh, E. Dotan, D. Catenacci, E. Van Cutsem, C. Lihou, H. Ren, K. Bibeau, L. Feliz, A. Vogel
Journal: Annals of Oncology (2021)
MicroRNA-27b-3p down-regulates <i>FGF1</i> and aggravates pathological cardiac remodelling
Authors: Guoqi Li, Yihui Shao, Hong Chang Guo, Ying Zhi, Bokang Qiao, Ke Ma, Jie Du, Yong Qiang Lai, Yulin Li
Journal: Cardiovascular Research (2021)

Abstract Aims The heart undergoes pathological remodelling under increased stress and neuronal imbalance. MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remodelling remain to be studied. This study aimed to explore the function of endogenous microRNA-27b-3p (miR-27b-3p) in pathological cardiac remodelling. Methods and results miR-27b-3p expression was elevated in the heart of a transverse aortic constriction (TAC)-induced cardiac hypertrophy mouse model. miR-27b-knockout mice showed significantly attenuated cardiac hypertrophy, fibrosis, and inflammation induced by two independent pathological cardiac hypertrophy models, TAC and Angiotensin II (Ang II) perfusion. Transcriptome sequencing analysis revealed that miR-27b deletion significantly down-regulated TAC-induced cardiac hypertrophy, fibrosis, and inflammatory genes. We identified fibroblast growth factor 1 (FGF1) as a miR-27b-3p target gene in the heart which was up-regulated in miR-27b-null mice. We found that both recombinant FGF1 (rFGF1) and inhibition of miR-27b-3p enhanced mitochondrial oxidative phosphorylation (OXPHOS) and inhibited cardiomyocyte hypertrophy. Importantly, rFGF1 administration inhibited cardiac hypertrophy and fibrosis in TAC- or Ang II-induced models and enhanced OXPHOS by activating PGC1α/β. Conclusions Our study demonstrated that miR-27b-3p induces pathological cardiac remodelling and suggests that inhibition of endogenous miR-27b-3p or administration of FGF1 might have the potential to suppress cardiac remodelling in a clinical setting.
Human-Mediated Admixture and Selection Shape the Diversity on the Modern Swine (<i>Sus scrofa</i>) Y Chromosomes
Authors: Huashui Ai, Mingpeng Zhang, Bin Yang, Amy Goldberg, Wanbo Li, Junwu Ma, Debora Brandt, Zhiyan Zhang, Rasmus Nielsen, Lusheng Huang
Journal: Molecular Biology and Evolution (2021)

Abstract Throughout its distribution across Eurasia, domestic pig (Sus scrofa) populations have acquired differences through natural and artificial selection, and have often interbred. We resequenced 80 Eurasian pigs from nine different Asian and European breeds; we identify 42,288 reliable SNPs on the Y chromosome in a panel of 103 males, among which 96.1% are newly detected. Based on these new data, we elucidate the evolutionary history of pigs through the lens of the Y chromosome. We identify two highly divergent haplogroups: one present only in Asia and one fixed in Europe but present in some Asian populations. Analyzing the European haplotypes present in Asian populations, we find evidence of three independent waves of introgression from Europe to Asia in last 200 years, agreeing well with the literature and historical records. The diverse European lineages were brought in China by humans and left significant imprints not only on the autosomes but also on the Y chromosome of geographically and genetically distinct Chinese pig breeds. We also find a general excess of European ancestry on Y chromosomes relative to autosomes in Chinese pigs, an observation that cannot be explained solely by sex-biased migration and genetic drift. The European Y haplotype is associated with leaner meat production, and we hypothesize that the European Y chromosome increased in frequency in Chinese populations due to artificial selection. We find evidence of Y chromosomal gene flow between Sumatran wild boar and Chinese pigs. Our results demonstrate how human-mediated admixture and selection shaped the distribution of modern swine Y chromosomes.