tbuckley/cabot-search huggingface dataset:
Association Between Diabetes and Gray Matter Atrophy Patterns in a General Older Japanese Population: The Hisayama Study
Authors: Naoki Hirabayashi, Jun Hata, Yoshihiko Furuta, Tomoyuki Ohara, Mao Shibata, Yoichiro Hirakawa, Fumio Yamashita, Kazufumi Yoshihara, Takanari Kitazono, Nobuyuki Sudo, Toshiharu Ninomiya
Journal: Diabetes Care (2022)

OBJECTIVE To examine the association between diabetes and gray matter atrophy patterns in a general older Japanese population. RESEARCH DESIGN AND METHODS In 2012, a total of 1,189 community-dwelling Japanese aged ≥65 years underwent brain MRI scans. Regional gray matter volumes (GMV) and intracranial volume (ICV) were measured by applying voxel-based morphometry (VBM) methods. The associations of diabetes and related parameters with the regional GMV/ICV were examined using an ANCOVA. The regional gray matter atrophy patterns in the subjects with diabetes or elevated fasting plasma glucose (FPG) or 2-h postload glucose (2hPG) levels were investigated using VBM. RESULTS Subjects with diabetes had significantly lower mean values of GMV/ICV in the frontal lobe, temporal lobe, insula, deep gray matter structures, and cerebellum than subjects without diabetes after adjusting for potential confounders. A longer duration of diabetes was also significantly associated with lower mean values of GMV/ICV in these brain regions. The multivariable-adjusted mean values of the temporal, insular, and deep GMV/ICV decreased significantly with elevating 2hPG levels, whereas higher FPG levels were not significantly associated with GMV/ICV of any brain regions. In the VBM analysis, diabetes was associated with gray matter atrophy in the bilateral superior temporal gyri, right middle temporal gyrus, left inferior temporal gyrus, right middle frontal gyrus, bilateral thalami, right caudate, and right cerebellum. CONCLUSIONS The current study suggests that a longer duration of diabetes and elevated 2hPG levels are significant risk factors for gray matter atrophy in various brain regions.
Glutaminase inhibition impairs CD8 T cell activation in STK11-/Lkb1-deficient lung cancer
Authors: Sarah A. Best, Patrick M. Gubser, Shalini Sethumadhavan, Ariena Kersbergen, Yashira L. Negrón Abril, Joshua Goldford, Katherine Sellers, Waruni Abeysekera, Alexandra L. Garnham, Jackson A. McDonald, Clare E. Weeden, Dovile Anderson, David Pirman, Thomas P. Roddy, Darren J. Creek, Axel Kallies, Gillian Kingsbury, Kate D. Sutherland
Journal: Cell Metabolism (2022)

The tumor microenvironment (TME) contains a rich source of nutrients that sustains cell growth and facilitate tumor development. Glucose and glutamine in the TME are essential for the development and activation of effector T cells that exert antitumor function. Immunotherapy unleashes T cell antitumor function, and although many solid tumors respond well, a significant proportion of patients do not benefit. In patients with KRAS-mutant lung adenocarcinoma, KEAP1 and STK11/Lkb1 co-mutations are associated with impaired response to immunotherapy. To investigate the metabolic and immune microenvironment of KRAS-mutant lung adenocarcinoma, we generated murine models that reflect the KEAP1 and STK11/Lkb1 mutational landscape in these patients. Here, we show increased glutamate abundance in the Lkb1-deficient TME associated with CD8 T cell activation in response to anti-PD1. Combination treatment with the glutaminase inhibitor CB-839 inhibited clonal expansion and activation of CD8 T cells. Thus, glutaminase inhibition negatively impacts CD8 T cells activated by anti-PD1 immunotherapy.
A T cell resilience model associated with response to immunotherapy in multiple tumor types
Authors: Yu Zhang, Trang Vu, Douglas C. Palmer, Rigel J. Kishton, Lanqi Gong, Jiao Huang, Thanh Nguyen, Zuojia Chen, Cari Smith, Ferenc Livák, Rohit Paul, Chi-Ping Day, Chuan Wu, Glenn Merlino, Kenneth Aldape, Xin-yuan Guan, Peng Jiang
Journal: Nature Medicine (2022)
Incidence of Sudden Cardiac Death in the European Union
Authors: Jean-Philippe Empana, Ivan Lerner, Eugenie Valentin, Fredrik Folke, Bernd Böttiger, Gunnar Gislason, Martin Jonsson, Mattias Ringh, Frankie Beganton, Wulfran Bougouin, Eloi Marijon, Marieke Blom, Hanno Tan, Xavier Jouven
Journal: Journal of the American College of Cardiology (2022)

Although sudden cardiac death (SCD) is recognized as a high-priority public health topic, reliable estimates of the incidence of SCD or, more broadly, out-of-hospital cardiac arrest (OHCA), in the population are scarce, especially in the European Union.The study objective was to determine the incidence of SCD and OHCA in the European Union.The study examined 4 large (ie, >2 million inhabitants) European population-based prospective registries collecting emergency medical services (EMS)-attended (ie, with attempted resuscitation) OHCA and SCD (OHCA without obvious extracardiac causes) for >5 consecutive years from January 2012 to December 2017 in the Paris region (France), the North Holland region (the Netherlands), the Stockholm region (Sweden), and in all of Denmark.The average annual incidence of SCD in the 4 registries ranged from 36.8 per 100,000 (95% CI: 23.5-50.1 per 100,000) to 39.7 per 100,000 (95% CI: 32.6-46.8 per 100,000). When extrapolating to each European country and accounting for age and sex, this yields to 249,538 SCD cases per year (95% CI: 155,377-343,719 SCD cases per year). The average annual incidence of OHCA in the 4 registries ranged from 47.8 per 100,000 (95% CI: 21.2-74.4 per 100,000) to 57.9 per 100,000 (95% CI: 19.6-96.3 per 100,000), corresponding to 343,496 OHCA cases per year (95% CI: 216,472-464,922 OHCA cases per year) in the European Union. Incidence rates of SCD and OHCA increased with age and were systematically higher in men compared with women.By combining data from 4 large, population-based registries with at least 5 years of data collection, this study provided an estimate of the incidence of SCD and OHCA in the European Union.
Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis
Authors: Elizabeth Costello, Sarah Rock, Nikos Stratakis, Sandrah P. Eckel, Douglas I. Walker, Damaskini Valvi, Dora Cserbik, Todd Jenkins, Stavra A. Xanthakos, Rohit Kohli, Stephanie Sisley, Vasilis Vasiliou, Michele A. La Merrill, Hugo Rosen, David V. Conti, Rob McConnell, Leda Chatzi
Journal: Environmental Health Perspectives (2022)

Background: Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry and consumer products and bioaccumulate in food webs and human tissues, such as the liver. Objective: The objective of this study was to conduct a systematic review of the literature and meta-analysis evaluating PFAS exposure and evidence of liver injury from rodent and epidemiological studies. Methods: PubMed and Embase were searched for all studies from earliest available indexing year through 1 December 2021 using keywords corresponding to PFAS exposure and liver injury. For data synthesis, results were limited to studies in humans and rodents assessing the following indicators of liver injury: serum alanine aminotransferase (ALT), nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, or steatosis. For human studies, at least three observational studies per PFAS were used to conduct a weighted z-score meta-analysis to determine the direction and significance of associations. For rodent studies, data were synthesized to qualitatively summarize the direction and significance of effect. Results: Our search yielded 85 rodent studies and 24 epidemiological studies, primarily of people from the United States. Studies focused primarily on legacy PFAS: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid. Meta-analyses of human studies revealed that higher ALT levels were associated with exposure to PFOA (z-score= 6.20, p<0.001), PFOS (z-score= 3.55, p<0.001), and PFNA (z-score= 2.27, p=0.023). PFOA exposure was also associated with higher aspartate aminotransferase and gamma-glutamyl transferase levels in humans. In rodents, PFAS exposures consistently resulted in higher ALT levels and steatosis. Conclusion: There is consistent evidence for PFAS hepatotoxicity from rodent studies, supported by associations of PFAS and markers of liver function in observational human studies. This review identifies a need for additional research evaluating next-generation PFAS, mixtures, and early life exposures. https://doi.org/10.1289/EHP10092
Revisiting the Threshold for Cancer Genetics Referral in Patients With Wilms Tumor
Authors: Joyce T. Turner, D. Ashley Hill, Jeffrey S. Dome
Journal: Journal of Clinical Oncology (2022)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology , to patients seen in their own clinical practice.
In vitro and in vivo investigation of a zonal microstructured scaffold for osteochondral defect repair
Authors: Joseph A.M. Steele, Axel C. Moore, Jean-Philippe St-Pierre, Seth D. McCullen, Adam J. Gormley, Conor C. Horgan, Cameron RM. Black, Christoph Meinert, Travis Klein, Siamak Saifzadeh, Roland Steck, Jiongyu Ren, Maria A. Woodruff, Molly M. Stevens
Journal: Biomaterials (2022)

Articular cartilage is comprised of zones that vary in architecture, extracellular matrix composition, and mechanical properties. Here, we designed and engineered a porous zonal microstructured scaffold from a single biocompatible polymer (poly [ϵ-caprolactone]) using multiple fabrication strategies: electrospinning, spherical porogen leaching, directional freezing, and melt electrowriting. With this approach we mimicked the zonal structure of articular cartilage and produced a stiffness gradient through the scaffold which aligns with the mechanics of the native tissue. Chondrocyte-seeded scaffolds accumulated extracellular matrix including glycosaminoglycans and collagen II over four weeks in vitro. This prompted us to further study the repair efficacy in a skeletally mature porcine model. Two osteochondral lesions were produced in the trochlear groove of 12 animals and repaired using four treatment conditions: (1) microstructured scaffold, (2) chondrocyte seeded microstructured scaffold, (3) MaioRegen™, and (4) empty defect. After 6 months the defect sites were harvested and analyzed using histology, micro computed tomography, and Raman microspectroscopy mapping. Overall, the scaffolds were retained in the defect space, repair quality was repeatable, and there was clear evidence of osteointegration. The repair quality of the microstructured scaffolds was not superior to the control based on histological scoring; however, the lower score was biased by the lack of histological staining due to the limited degradation of the implant at 6 months. Longer follow up studies (e.g., 1 yr) will be required to fully evaluate the efficacy of the microstructured scaffold. In conclusion, we found consistent scaffold retention, osteointegration, and prolonged degradation of the microstructured scaffold, which we propose may have beneficial effects for the long-term repair of osteochondral defects.
Autopsies in COVID-related deaths: The need for following the model of German COVID-19 autopsy registry
Authors: Cristoforo Pomara, Monica Salerno, Alessandro Miani, Prisco Piscitelli
Journal: The Lancet Regional Health - Europe (2022)

Autopsies are an important tool in medicine, dissecting disease pathophysiology and causes of death, thus representing a valuable practice to improve our knowledge for public health purposes, also about COVID-19.As shown by von Stillfried et al., the experience of the German COVID-19 Autopsy Registry (DeRegCOVID), launched in 2020, revealed the effects of SARS-COV2 on pulmonary micro-vessels, as well as the involvement of the nervous system in the frame of systemic viral spread. 1 There is radiological evidence that some COVID-19 patients affected from pneumonia can develop severe respiratory distress, and frequently coagulopathy, thus generating acute pulmonary embolism caused by in-situ thrombosis due to interstitial COVID-19 injury. 2
Opsonized nanoparticles target and regulate macrophage polarization for osteoarthritis therapy: A trapping strategy
Authors: Longfa Kou, Huirong Huang, Yingying Tang, Meng Sun, Yingtao Li, Jianing Wu, Shimin Zheng, Xinyu Zhao, Daosen Chen, Zucheng Luo, Xiaolei Zhang, Qing Yao, Ruijie Chen
Journal: Journal of Controlled Release (2022)
In This Issue
Journal: Cancer Discovery (2022)

Neuregulin 1 (NRG1) fusion proteins, which occur in many tumor types, bind HER3 and induce its dimerization with other HER/ERBB kinases, thereby promoting downstream oncogenic signaling and tumorigenesis.Because targeting HER2 and/or HER3 has been shown to be effective in NRG1-rearranged tumor models, Schram, Odintsov, and colleagues investigated zenocutuzumab, a HER2xHER3 bispecific antibody, in NRG1rearranged tumors.In preclinical models of lung, breast, pancreas, and ovarian NRG1-rearranged tumors, zenocutuzumab reduced cell growth and HER3 and AKT phosphorylation and induced apoptosis.Three patients with NRG1 fusion-positive metastatic cancers were treated with zenocutuzumab and had a partial response, supporting its ongoing clinical evaluation in NRG1 fusion-positive cancers.
Genomic variations and epigenomic landscape of the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel
Authors: Adrien Leger, Ian Brettell, Jack Monahan, Carl Barton, Nadeshda Wolf, Natalja Kusminski, Cathrin Herder, Narendar Aadepu, Clara Becker, Jakob Gierten, Omar T. Hammouda, Eva Hasel, Colin Lischik, Katharina Lust, Natalia Sokolova, Risa Suzuki, Tinatini Tavhelidse, Thomas Thumberger, Erika Tsingos, Philip Watson, Bettina Welz, Kiyoshi Naruse, Felix Loosli, Joachim Wittbrodt, Ewan Birney, Tomas Fitzgerald
Journal: Genome biology (2022)

Abstract Background The teleost medaka ( Oryzias latipes ) is a well-established vertebrate model system, with a long history of genetic research, and multiple high-quality reference genomes available for several inbred strains. Medaka has a high tolerance to inbreeding from the wild, thus allowing one to establish inbred lines from wild founder individuals. Results We exploit this feature to create an inbred panel resource: the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel. This panel of 80 near-isogenic inbred lines contains a large amount of genetic variation inherited from the original wild population. We use Oxford Nanopore Technologies (ONT) long read data to further investigate the genomic and epigenomic landscapes of a subset of the MIKK panel. Nanopore sequencing allows us to identify a large variety of high-quality structural variants, and we present results and methods using a pan-genome graph representation of 12 individual medaka lines. This graph-based reference MIKK panel genome reveals novel differences between the MIKK panel lines and standard linear reference genomes. We find additional MIKK panel-specific genomic content that would be missing from linear reference alignment approaches. We are also able to identify and quantify the presence of repeat elements in each of the lines. Finally, we investigate line-specific CpG methylation and performed differential DNA methylation analysis across these 12 lines. Conclusions We present a detailed analysis of the MIKK panel genomes using long and short read sequence technologies, creating a MIKK panel-specific pan genome reference dataset allowing for investigation of novel variation types that would be elusive using standard approaches.
Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden
Authors: Bronner P Gonçalves, Simon R Procter, Proma Paul, Jaya Chandna, Alexandra Lewin, Farah Seedat, Artemis Koukounari, Ziyaad Dangor, Shannon Leahy, Sridhar Santhanam, Hima B John, Justina Bramugy, Azucena Bardají, Amina Abubakar, Carophine Nasambu, Romina Libster, Clara Sánchez Yanotti, Erzsébet Horváth-Puhó, Henrik T Sørensen, Diederik van de Beek, Merijn W Bijlsma, William M Gardner, Nicholas Kassebaum, Caroline Trotter, Quique Bassat, Shabir A Madhi, Philipp Lambach, Mark Jit, Joy E Lawn, Kirstine K. Søgaard, Merel N. van Kassel, Linde Snoek, Brechje de Gier, Arie van der Ende, Susan J M Hahné, Lois M. Harden, Azra Ghoor, Sibongile Mbatha, Sarah Lowick, Barbara Laughton, Tamara Jaye, Sanjay G Lala, Pamela Sithole, Jacqueline Msayi, Ntombifuthi Kumalo, Tshepiso Nompumelelo Msibi, Asha Arumugam, Nandhini Murugesan, Nandhini Rajendraprasad, Mohana Priya, Adam Mabrouk, Patrick Vidzo Katana, Eva Mwangome, Charles R. Newton, Humberto Mucasse, Celine Aerts, Sergio Massora, Valeria Medina, Andrea Rojas, Daniel Amado, Conrado J. Llapur, A. K. M. Tanvir Hossain, Qazi Sadeq-ur Rahman, Margaret Ip, Anna Seale, Paul T. Heath, Kirsty Le Doare, Asma Khalil, Stephanie J. Schrag, Ajoke Sobanjo-ter Meulen, Elizabeth Mason, Dianna M Blau, Shams El Arifeen, Nega Assefa, Dickens Onyango, Samba O. Sow, Inacio Mandomando, Ikechukwu Ogbuanu, Karen L. Kotloff, J. Anthony G. Scott, Emily S. Gurley, Beth A. Tippet Barr, Sana Mahtab
Journal: The Lancet Global Health (2022)

Group B streptococcus (GBS) colonisation during pregnancy can lead to invasive GBS disease (iGBS) in infants, including meningitis or sepsis, with a high mortality risk. Other outcomes include stillbirths, maternal infections, and prematurity. There are data gaps, notably regarding neurodevelopmental impairment (NDI), especially after iGBS sepsis, which have limited previous global estimates. In this study, we aimed to address this gap using newly available multicountry datasets.
Regional vs General Anesthesia and Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery—Reply
Authors: Ting Li, Chenchen Jiang, Fang Gao Smith
Journal: JAMA (2022)

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
<i>cfTrack</i>: A Method of Exome-Wide Mutation Analysis of Cell-free DNA to Simultaneously Monitor the Full Spectrum of Cancer Treatment Outcomes Including MRD, Recurrence, and Evolution
Authors: Shuo Li, Weihua Zeng, Xiaohui Ni, Yonggang Zhou, Mary L. Stackpole, Zorawar S. Noor, Zuyang Yuan, Adam Neal, Sanaz Memarzadeh, Edward B. Garon, Steven M. Dubinett, Wenyuan Li, Xianghong Jasmine Zhou
Journal: Clinical Cancer Research (2022)

Cell-free DNA (cfDNA) offers a noninvasive approach to monitor cancer. Here we develop a method using whole-exome sequencing (WES) of cfDNA for simultaneously monitoring the full spectrum of cancer treatment outcomes, including minimal residual disease (MRD), recurrence, evolution, and second primary cancers.Three simulation datasets were generated from 26 patients with cancer to benchmark the detection performance of MRD/recurrence and second primary cancers. For further validation, cfDNA samples (n = 76) from patients with cancer (n = 35) with six different cancer types were used for performance validation during various treatments.We present a cfDNA-based cancer monitoring method, named cfTrack. Taking advantage of the broad genome coverage of WES data, cfTrack can sensitively detect MRD and cancer recurrence by integrating signals across known clonal tumor mutations of a patient. In addition, cfTrack detects tumor evolution and second primary cancers by de novo identifying emerging tumor mutations. A series of machine learning and statistical denoising techniques are applied to enhance the detection power. On the simulation data, cfTrack achieved an average AUC of 99% on the validation dataset and 100% on the independent dataset in detecting recurrence in samples with tumor fractions ≥0.05%. In addition, cfTrack yielded an average AUC of 88% in detecting second primary cancers in samples with tumor fractions ≥0.2%. On real data, cfTrack accurately monitors tumor evolution during treatment, which cannot be accomplished by previous methods.Our results demonstrated that cfTrack can sensitively and specifically monitor the full spectrum of cancer treatment outcomes using exome-wide mutation analysis of cfDNA.
Missed Signs of Acute Pulmonary Embolism in Electrocardiogram Findings
Authors: Ting-Ting Li, Xiaohong Chen
Journal: JAMA Internal Medicine (2022)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Internal Medicine journal