tbuckley/cabot-search huggingface dataset:
Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): A multicentre, randomised, double-blinded, placebo-controlled trial
Authors: Anadeijda J. E. M. C. Landman, Marjon A. de Boer, Laura Visser, Tobias A. J. Nijman, Marieke A. C. Hemels, Christiana N. Naaktgeboren, Marijke C. van der Weide, Ben W. Mol, Judith O. E. H. van Laar, Dimitri N. M. Papatsonis, Mireille N. Bekker, Joris van Drongelen, Mariëlle G. van Pampus, Marieke Sueters, David P. van der Ham, J. Marko Sikkema, Joost J. Zwart, Anjoke J. M. Huisjes, Marloes E. van Huizen, Gunilla Kleiverda, Janine Boon, Maureen T. M. Franssen, Wietske Hermes, Harry Visser, Christianne J. M. de Groot, Martijn A. Oudijk
Journal: PLoS Medicine (2022)

Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth.
Minimum Standards for the Commercial Production of Randombred and Inbred Laboratory Rats&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;4&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1959)

Minimum Standards for the Commercial Production of Randombred and Inbred Laboratory Rats234 JNCI: Journal of the National Cancer Institute, Volume 22, Issue 4, April 1959, Pages 869–876, https://doi.org/10.1093/jnci/22.4.869 Published: 01 April 1959 Article history Received: 28 December 1958 Published: 01 April 1959
Pediatrics
Authors: Marilyn Heins
Journal: JAMA (1989)

Both the specialty of pediatrics and the children it serves have benefited from the recent advances in biomedical science and technology. Each year brings new triumphs—but regrettably also brings tragedies, which can be defined as a greater discrepancy between the gains for some children and the status quo (or worse) for others. First, the triumphs. Advances in molecular genetics are impacting on clinical pediatrics. The gene for cystic fibrosis has been located on chromosome 7 and antenatal diagnosis, using linked DNA probes of fetal DNA from chorionic villi sampling, is now possible in more than two thirds of parents with an affected child. Sickle cell anemia can also be diagnosed before birth; a new restrictive enzyme technique can make the diagnosis in a day.<sup>1</sup>Recent gene mapping studies have shown that the gene frequency of nonclassical adrenal hyperplasia is more common than cystic fibrosis in white populations.<sup>2</sup>Gene replacement
Placing Ancient DNA Sequences into Reference Phylogenies
Authors: Rui Martiniano, Bianca De Sanctis, Pille Hallast, Richard Durbin
Journal: Molecular Biology and Evolution (2022)

Joint phylogenetic analysis of ancient DNA (aDNA) with modern phylogenies is hampered by low sequence coverage and post-mortem deamination, often resulting in overconservative or incorrect assignment. We provide a new efficient likelihood-based workflow, pathPhynder, that takes advantage of all the polymorphic sites in the target sequence. This effectively evaluates the number of ancestral and derived alleles present on each branch and reports the most likely placement of an ancient sample in the phylogeny and a haplogroup assignment, together with alternatives and supporting evidence. To illustrate the application of pathPhynder, we show improved Y chromosome assignments for published aDNA sequences, using a newly compiled Y variation data set (120,908 markers from 2,014 samples) that significantly enhances Y haplogroup assignment for low coverage samples. We apply the method to all published male aDNA samples from Africa, giving new insights into ancient migrations and the relationships between ancient and modern populations. The same software can be used to place samples with large amounts of missing data into other large non-recombining phylogenies such as the mitochondrial tree.
Shape‐Anisotropic Microembolics Generated by Microfluidic Synthesis for Transarterial Embolization Treatment
Authors: Yucheng Luo, Yutao Ma, Zijian Chen, Yanan Gao, Yuping Zhou, Xiaoya Liu, Xuezhe Liu, Xu Gao, Zhihua Li, Chuang Liu, Hwa Liang Leo, Hanry Yu, Qiongyu Guo
Journal: Advanced Healthcare Materials (2022)

Abstract Particulate embolic agents with calibrated sizes, which employ interventional procedures to achieve endovascular embolization, have recently attracted tremendous interest in therapeutic embolotherapies for a wide plethora of diseases. However, the particulate shape effect, which may play a critical role in embolization performances, has been rarely investigated. Here, polyvinyl alcohol (PVA)‐based shape‐anisotropic microembolics are developed using a facile droplet‐based microfluidic fabrication method via heat‐accelerated PVA‐glutaraldehyde crosslinking reaction at a mild temperature of 38 ° C. Precise geometrical controls of the microembolics are achieved with a nearly capsule shape through regulating surfactant concentration and flow rate ratio between dispersed phase and continuous phase in the microfluidics. Two specific models are employed, i.e., in vitro decellularized rabbit liver embolization model and in vivo rabbit ear embolization model, to systematically evaluate the embolization behaviors of the nonspherical microembolics. Compared to microspheres of the same volume, the elongated microembolics demonstrated advantageous endovascular navigation capability, penetration depth and embolization stability due to their comparatively smaller radial diameter and their central cylindrical part providing larger contact area with distal vessels. Such nonspherical microembolics present a promising platform to apply shape anisotropy to achieve distinctive therapeutic effects for endovascular treatments.
Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification
Authors: Yiyang Hu, Chunli Gong, Zhibin Li, Jiao Liu, Yang Chen, Yu Huang, Qiang Luo, Sumin Wang, Yu Hou, Shiming Yang, Yufeng Xiao
Journal: Molecular Cancer (2022)

Abstract Background Gastric cancer (GC) is one of the most pernicious tumors that seriously harm human healthcare. GC metastasis is one of the prime cause of failed cancer treatment, but correlation between N6-methyladenosine (m6A) and GC metastasis was less reported. Methods Methylated RNA immunoprecipitation sequencing (MeRIP-seq) of GC tissues was conducted. Quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry (IHC) were taken to determine the expression of ALKBH5 in GC tissues and cell lines. RNA-seq together with MeRIP-qRT-PCR was used to screen the target gene of ALKBH5. RNA pulldown, mass spectrometry and RNA immunoprecipitation (RIP) were used to search the “reader” protein of target gene. The mechanism was also validated via a tail vein injection method for lung metastasis model. Results Decreased expression of ALKBH5 was detected in GC samples, and it was correlated with clinical tumor distal metastasis and lymph node metastasis. ALKBH5 interference promoted metastasis of GC cells and this effect was closely related to the demethylase activity of ALKBH5. PKMYT1, as a downstream target of ALKBH5, promoted invasion and migration in GC. Caused by ALKBH5 knockdown or its demethylase activity mutation, upregulated expression of PKMYT1 indicated that ALKBH5 modulates expression of PKMYT1 in an m6A-dependent manner. IGF2BP3 helped stabilize the mRNA stability of PKMYT1 via its m6A modification site. Conclusions This study established an ALKBH5-PKMYT1-IGF2BP3 regulation system in metastasis, representing a new therapeutic target for GC metastasis.
Tumor mutation burden for predicting immune checkpoint blockade response: the more, the better
Authors: Ming Zheng
Journal: Journal for ImmunoTherapy of Cancer (2022)

Recently, the US Food and Drug Administration (FDA) has approved immune checkpoint blockade (ICB) for treating cancer patients with tumor mutation burden (TMB) >10 mutations/megabase (mut/Mb). However, high TMB (TMB-H) defined by >10 mut/Mb fails to predict ICB response across different cancer types, which has raised serious concerns on the current FDA approval. Thus, to better implement TMB as a robust biomarker of ICB response, an optimal and generalizable TMB cut-off within and across cancer types must be addressed as soon as possible.Using Morris's and Kurzrock's cohorts (n=1662 and 102), we exhaustively tested all possible TMB cut-offs for predicting ICB treatment outcomes in 10 cancer types. The bootstrap method was applied to generate 10,000 randomly resampled cohorts using original cohorts to measure the reproducibility of TMB cut-off. ICB treatment outcomes were analyzed by overall survival, progression-free survival and objective response rate.No universally valid TMB cut-off was available for all cancer types. Only in cancer types with higher TMB (category I), such as melanoma, colorectal cancer, bladder cancer, and non-small cell lung cancer, the associations between TMB-H and ICB treatment outcomes were less affected by TMB cut-off selection. Moreover, high TMB (category I) cancer types shared a wide range of TMB cut-offs and a universally optimal TMB cut-off of 13 mut/Mb for predicting favorable ICB outcomes. In contrast, low TMB (category II) cancer types, for which the prognostic associations were sensitive to TMB cut-off selection, showed markedly limited and distinct ranges of significantly favorable TMB cut-offs. Equivalent results were obtained in the analyses of pooled tumors.Our finding-the correlation that TMB-H is more robustly associated with favorable ICB treatment outcomes in cancer types with higher TMBs-can be used to predict whether TMB could be a robust predictive biomarker in cancer types for which TMB data are available, but ICB treatment has not been investigated. This theory was tested in cancer of unknown primary successfully. Additionally, the universal TMB cut-off of 13 mut/Mb might reveal a general requirement to trigger the sequential cascade from somatic mutations to an effective antitumor immunity.
Fertility and Sterility, New York
Journal: JAMA (1964)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Type 2 Diabetes Partitioned Polygenic Scores Associate With Disease Outcomes in 454,193 Individuals Across 13 Cohorts
Authors: Daniel DiCorpo, Jessica LeClair, Joanne B. Cole, Chloé Sarnowski, Fariba Ahmadizar, Lawrence F. Bielak, Anneke Blokstra, Erwin P. Bottinger, Layal Chaker, Yii-Der I. Chen, Ye Chen, Paul S. de Vries, Tariq Faquih, Mohsen Ghanbari, Valborg Gudmundsdottir, Xiuqing Guo, Natalie R. Hasbani, Dorina Ibi, M. Arfan Ikram, Maryam Kavousi, Hampton L. Leonard, Aaron Leong, Josep M. Mercader, Alanna C. Morrison, Girish N. Nadkarni, Mike A. Nalls, Raymond Noordam, Michael Preuss, Jennifer A. Smith, Stella Trompet, Petra Vissink, Jie Yao, Wei Zhao, Eric Boerwinkle, Mark O. Goodarzi, Vilmundur Gudnason, J. Wouter Jukema, Sharon L.R. Kardia, Ruth J.F. Loos, Ching-Ti Liu, Alisa K. Manning, Dennis Mook-Kanamori, James S. Pankow, H. Susan J. Picavet, Naveed Sattar, Eleanor M. Simonsick, W.M. Monique Verschuren, Ko Willems van Dijk, Jose C. Florez, Jerome I. Rotter, James B. Meigs, Josée Dupuis, Miriam S. Udler
Journal: Diabetes Care (2022)

OBJECTIVE Type 2 diabetes (T2D) has heterogeneous patient clinical characteristics and outcomes. In previous work, we investigated the genetic basis of this heterogeneity by clustering 94 T2D genetic loci using their associations with 47 diabetes-related traits and identified five clusters, termed β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. The relationship between these clusters and individual-level metabolic disease outcomes has not been assessed. RESEARCH DESIGN AND METHODS Here we constructed individual-level partitioned polygenic scores (pPS) for these five clusters in 12 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (n = 454,193) and tested for cross-sectional association with T2D-related outcomes, including blood pressure, renal function, insulin use, age at T2D diagnosis, and coronary artery disease (CAD). RESULTS Despite all clusters containing T2D risk-increasing alleles, they had differential associations with metabolic outcomes. Increased obesity and lipodystrophy cluster pPS, which had opposite directions of association with measures of adiposity, were both significantly associated with increased blood pressure and hypertension. The lipodystrophy and liver/lipid cluster pPS were each associated with CAD, with increasing and decreasing effects, respectively. An increased liver/lipid cluster pPS was also significantly associated with reduced renal function. The liver/lipid cluster includes known loci linked to liver lipid metabolism (e.g., GCKR, PNPLA3, and TM6SF2), and these findings suggest that cardiovascular disease risk and renal function may be impacted by these loci through their shared disease pathway. CONCLUSIONS Our findings support that genetically driven pathways leading to T2D also predispose differentially to clinical outcomes.
Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer
Authors: Sibi Raj, Kavindra Kumar Kesari, Arun Kumar, Brijesh Rathi, Ashok Sharma, Piyush Kumar Gupta, Saurabh Kumar Jha, Niraj Kumar Jha, Petr Slama, Shubhadeep Roychoudhury, Dhruv Kumar
Journal: Molecular Cancer (2022)

Abstract Head and neck cancer is the sixth most common cancer across the globe. This is generally associated with tobacco and alcohol consumption. Cancer in the pharynx majorly arises through human papillomavirus (HPV) infection, thus classifying head and neck squamous cell carcinoma (HNSCC) into HPV-positive and HPV-negative HNSCCs. Aberrant, mesenchymal-epithelial transition factor (c-MET) signal transduction favors HNSCC progression by stimulating proliferation, motility, invasiveness, morphogenesis, and angiogenesis. c-MET upregulation can be found in the majority of head and neck squamous cell carcinomas. c-MET pathway acts on several downstream effectors including phospholipase C gamma (PLCγ), cellular Src kinase (c-Src), phosphotidylinsitol-3-OH kinase (PI3K), alpha serine/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK), and wingless-related integration site (Wnt) pathways. c-MET also establishes a crosstalk pathway with epidermal growth factor receptor (EGFR) and contributes towards chemoresistance in HNSCC. In recent years, the signaling communications of c-MET/HGF in metabolic dysregulation, tumor-microenvironment and immune modulation in HNSCC have emerged. Several clinical trials have been established against c-MET/ hepatocyte growth factor (HGF) signaling network to bring up targeted and effective therapeutic strategies against HNSCC. In this review, we discuss the molecular mechanism(s) and current understanding of c-MET/HGF signaling and its effect on HNSCC. Graphical abstract
S130: PROCESSING SPEED DECLINES OVER TIME IN 4--25-YEAR-OLDS WITH SICKLE CELL DISEASE
Authors: E Walker, A Hood, F Kirkham, A Hogan, K Watkins
Journal: HemaSphere (2022)

Background: Alongside physiological symptoms, young people with sickle cell disease (SCD) may also experience cognitive difficulties, including poorer processing speed. Processing speed develops rapidly from birth to around mid-childhood, with steady improvements thereafter into a person’s mid-twenties (Anderson, 2002). Nonetheless, little is known about the dynamic developmental trajectory of processing speed for young people with SCD. Aims: This study, we aimed to investigate if the change in processing speed index (PSI) over time is significantly different between younger participants (aged under 8.99 years at first assessment) and older participants (over 9 years at first assessment) with SCD. Methods: One hundred and five participants with SCD aged 4 – 18 (N < 8.99 = 47; N > 9 = 58) at recruitment consented to follow-up IQ assessments (WPPSI-R, WISC-III, WAIS-R or WAIS-III) and MRI scans over two timepoints between 1992 -2003. A repeated measures linear mixed-effects regression model determined longitudinal change in PSI, examining the interaction between age (i.e., under 8.99 years and over 9 years) and timepoint, and controlling for infarct status (i.e., no infarct on MRI, silent infarction, or stroke). Results: Both younger and older participants experienced a decline in PSI over time, and this decline was largest for younger participants with no infarct. We found a significant main effect of age, F(1, 53) = 4.46, p = .04 and timepoint, F(1, 27) = 7.86, p = .009, but no significant effect of infarct status. The interaction between time-point and age approached significance, F(1, 27) = 2.97, p = .09. Conclusion: Our findings demonstrated that young people with SCD experienced significant decline in processing speed over time, with a larger decline occurring in participants aged under 9 years, regardless of infarct status. These findings highlight the importance of researching and monitoring PSI longitudinally in young people with SCD, to better understand the impacts of SCD an individual’s cognition, identify potential treatment effects and to ensure appropriate support is put in place.Figure 1.: Processing speed index at timepoint 1 and timepoint 2 for participants under 9 (median age 6 years) and over 9 (median age 13 years) years by cerebral infarct statusNote: Mean processing speed index in a typically developing sample is 100. SCI = silent cerebral infarction; T1 = timepoint 1; T2 = timepoint 2. References 1. Anderson et al, Child Neuropsychology 2002; 8:2
Evaluation of a local anesthetic agent. Prilocaine hydrochloride (Citanest)
Journal: JAMA (1967)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Nano-trapping CXCL13 reduces regulatory B cells in tumor microenvironment and inhibits tumor growth
Authors: Limei Shen, Jingjing Li, Qi Liu, Manisit Das, Wantong Song, Xueqiong Zhang, Karthik Tiruthani, Oleksandra Dorosheva, Haiyang Hu, Samuel K. Lai, Rihe Liu, Leaf Huang
Journal: Journal of Controlled Release (2022)
Surgical and anatomic factors predict development of leptomeningeal disease in patients with melanoma brain metastases
Authors: Stephen R Lowe, Christopher P Wang, Amanda Brisco, Junmin Whiting, John Arrington, Kamran Ahmed, Michael Yu, Timothy Robinson, Daniel Oliver, Arnold Etame, Nam Tran, Andre Beer Furlan, Solmaz Sahebjam, Sepideh Mokhtari, Yolanda Piña, Robert Macaulay, Peter Forsyth, Michael A Vogelbaum, James K C Liu
Journal: Neuro-Oncology (2022)

Leptomeningeal disease (LMD) is a devastating complication of systemic malignancy, of which there is an unclear etiology. The aim of this study is to determine if surgical or anatomic factors can predict LMD in patients with metastatic melanoma.A retrospective chart review was performed of 1162 patients treated at single institution for melanoma brain metastases (MBM). Patients with fewer than 3 months follow-up or lacking appropriate imaging were excluded. Demographic information, surgical, and anatomic data were collected.Eight hundred and twenty-seven patients were included in the final review. On multivariate analysis for the entire cohort, female gender, dural-based and intraventricular metastasis, and tumor bordering CSF spaces were associated with increased risk of LMD. Surgical resection was not significant for risk of LMD. On multivariate analysis of patients who have undergone surgical resection of a metastatic tumor, dural-based and intraventricular metastasis, ventricular entry during surgery, and metastasis in the infratentorial space were associated with increased risk of LMD. On multivariate analysis of patients who did not undergo surgery, chemotherapy after initial diagnosis and metastasis bordering CSF spaces were associated with increased risk of LMD.In a single-institution cohort of MBM, we found that surgical resection alone did not result in an increased risk of LMD. Anatomical factors such as dural-based and intraventricular metastasis were significant for developing LMD, as well as entry into a CSF space during surgical resection. These data suggest a strong correlation between anatomic location and tumor cell seeding in relation to the development of LMD.