tbuckley/cabot-search huggingface dataset:
Predicting sudden death … and other research
Authors: Ann Robinson
Journal: BMJ (2024)

Predicting sudden deathMy dad died of a sudden cardiac arrest when he was 48 years old.His death, like many similar cases, was never really explained.One recently discovered cause of sudden death is a genetic arrhythmia syndrome called calcium release deficiency syndrome (CRDS).Could a new test identify CRDS before it presents as a sudden death?
Low smoking exposure and development and prognosis of COPD over four decades: a population-based cohort study
Authors: Yunus Çolak, Anders Løkke, Jacob L. Marott, Peter Lange, Jørgen Vestbo, Børge G. Nordestgaard, Shoaib Afzal
Journal: European Respiratory Journal (2024)

Background A diagnosis of COPD is mainly considered in individuals with &gt;10 pack-years of smoking. We tested the hypothesis that low smoking exposure, below the critical threshold of 10 pack-years, increases risk of COPD and leads to poor prognosis. Methods We followed non-obstructed adult smokers from the Copenhagen City Heart Study for COPD, defined as a forced expiratory volume in 1 s (FEV 1 )/forced vital capacity &lt;0.70 and FEV 1 &lt;80% predicted, and for related clinical outcomes. First, we followed individuals for 5 years according to baseline smoking for risk of developing COPD, and thereafter for up to four decades for severe exacerbations and death. Results In 6098 non-obstructed smokers, 1781 (29%) developed COPD after 5 years of follow-up: 23% of individuals with &lt;10 pack-years of smoking at baseline, 26% of those with 10–19.9 pack-years, 30% of those with 20–39.9 pack-years and 39% of those with ≥40 pack-years. During four decades of follow-up, we recorded 620 exacerbations and 5573 deaths. Compared to individuals without COPD with &lt;10 pack‑years of smoking, multivariable adjusted hazard ratios (HRs) for exacerbations were 1.94 (95% CI 1.36–2.76) in those without COPD and ≥10 pack-years, 2.83 (95% CI 1.72–4.66) in those with COPD and &lt;10 pack-years, 4.34 (95% CI 2.93–6.43) in those with COPD and 10–19.9 pack-years, 4.39 (95% CI 2.98–6.46) in those with COPD and 20–39.9 pack-years and 4.98 (95% CI 3.11–7.97) in those with COPD and ≥40 pack-years. Corresponding HRs for all-cause mortality were 1.20 (95% CI 1.10–1.32), 1.31 (95% CI 1.13–1.53), 1.59 (95% CI 1.40–1.79), 1.81 (95% CI 1.62–2.03) and 1.81 (95% CI 1.55–2.10). Conclusion Low smoking exposure below the critical threshold of 10 pack-years increases risk of COPD in middle-aged adults within 5 years, and these individuals have increased risk of severe exacerbation and early death over four decades.
Treatment for Opioid Use Disorder: Population Estimates — United States, 2022
Authors: Deborah Dowell, Samantha Brown, Shiromani Gyawali, Jennifer Hoenig, Jean Ko, Christina Mikosz, Emily Ussery, Grant Baldwin, Christopher M. Jones, Yngvild Olsen, Naomi Tomoyasu, Beth Han, Wilson M. Compton, Nora D. Volkow
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

In 2022, 81,806 opioid-involved overdose deaths were reported in the United States, more than in any previous year.Medications for opioid use disorder (OUD), particularly buprenorphine and methadone, substantially reduce overdoserelated and overall mortality.However, only a small proportion of persons with OUD receive these medications.Data from the 2022 National Survey on Drug Use and Health were applied to a cascade of care framework to estimate and characterize U.S. adult populations who need OUD treatment, receive any OUD treatment, and receive medications for OUD.In 2022, 3.7% of U.S. adults aged ≥18 years needed OUD treatment.Among these, only 25.1% received medications for OUD.Most adults who needed OUD treatment either did not perceive that they needed it (42.7%)or received OUD treatment without medications for OUD (30.0%).Compared with non-Hispanic Black or African American and Hispanic or Latino adults, higher percentages of non-Hispanic White adults received any OUD treatment.Higher percentages of men and adults aged 35-49 years received medications for OUD than did women and younger or older adults.Expanded communication about the effectiveness of medications for OUD is needed.Increased efforts to engage persons with OUD in treatment that includes medications are essential.Clinicians and other treatment providers should offer or arrange evidence-based treatment, including medications, for patients with OUD.Pharmacists and payors can work to make these medications available without delays.
Persistent Transmission of Circulating Vaccine-Derived Poliovirus — Somalia, January 2017–March 2024
Authors: Amalia Mendes, Gedi Abdi Mohamed, Mohamed Derow, Tasha Stehling-Ariza, Abdinoor Mohamed, Kumlachew Mengistu, Kelley Bullard, Irfan Elahi Akbar, Hemant Shukla, Mohammad Al Safadi, Maureen Martinez
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Since the launch of the Global Polio Eradication Initiative in 1988, substantial progress has been made in the interruption of wild poliovirus (WPV) transmission worldwide: global eradication of WPV types 2 and 3 were certified in 2015 and 2019, respectively, and endemic transmission of WPV type 1 continues only in Afghanistan and Pakistan.After the synchronized global withdrawal of all serotype 2 oral poliovirus vaccines (OPVs) in 2016, widespread outbreaks of circulating vaccinederived poliovirus type 2 (cVDPV2) have occurred, which are linked to areas with low population immunity to poliovirus.Officials in Somalia have detected ongoing cVDPV2 transmission since 2017.Polio vaccination coverage and surveillance data for Somalia were reviewed to assess this persistent transmission.During January 2017-March 2024, officials in Somalia detected 39 cVDPV2 cases in 14 of 20 regions, and transmission has spread to neighboring Ethiopia and Kenya.Since January 2021, 28 supplementary immunization activities (SIAs) targeting cVDPV2 were conducted in Somalia.Some parts of the country are security-compromised and inaccessible for vaccination campaigns.Among 1,921 children with nonpolio acute flaccid paralysis, 231 (12%) had not received OPV doses through routine immunization or SIAs, 95% of whom were from the South-Central region, and 60% of whom lived in inaccessible districts.Enhancing humanitarian negotiation measures in Somalia to enable vaccination of children in security-compromised areas and strengthening campaign quality in accessible areas will help interrupt cVDPV2 transmission.
An electrocardiogram-based AI algorithm for early detection of pulmonary hypertension
Authors: Hilary M. DuBrock, Tyler E. Wagner, Katherine Carlson, Corinne L. Carpenter, Samir Awasthi, Zachi I. Attia, Robert P. Frantz, Paul A. Friedman, Suraj Kapa, Jeffrey Annis, Evan L. Brittain, Anna R. Hemnes, Samuel J. Asirvatham, Melwin Babu, Ashim Prasad, Unice Yoo, Rakesh Barve, Mona Selej, Peter Agron, Emily Kogan, Deborah Quinn, Preston Dunnmon, Najat Khan, Venky Soundararajan
Journal: European Respiratory Journal (2024)

Early diagnosis of pulmonary hypertension (PH) is critical for effective treatment and management. We aimed to develop and externally validate an artificial intelligence algorithm that could serve as a PH screening tool, based on analysis of a standard 12-lead ECG.
Optimisation of detecting chronic thromboembolic pulmonary hypertension in acute pulmonary embolism survivors: the InShape IV study
Authors: Dieuwke Luijten, Luca Valerio, Gudula J.A.M. Boon, Stefano Barco, Harm Jan Bogaard, Marion Delcroix, Yvonne Ende-Verhaar, Menno V. Huisman, Luis Jara-Palomares, Karl-Friedrich Kreitner, Lucia J.M. Kroft, Albert T.A. Mairuhu, Anna C. Mavromanoli, Lilian J. Meijboom, Thijs E. van Mens, Maarten K. Ninaber, Esther J. Nossent, Piotr Pruszczyk, Stephan Rosenkranz, Hubert Vliegen, Anton Vonk Noordegraaf, Stavros V. Konstantinides, Frederikus A. Klok
Journal: European Respiratory Journal (2024)

Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed late in acute pulmonary embolism survivors: more efficient testing to expedite diagnosis may considerably improve patient outcomes. The InShape II algorithm safely rules out CTEPH (failure rate 0.29%) while requiring echocardiography in only 19% of patients but may be improved by adding detailed reading of the computed tomography pulmonary angiography diagnosing the index pulmonary embolism.
The 2022 ERS/ATS z-score classification to grade airflow obstruction: relationship with exercise outcomes across the spectrum of COPD severity
Authors: Lamyaa Al Sa'idi, Danilo C. Berton, J. Alberto Neder
Journal: European Respiratory Journal (2024)

<h3>Shareable abstract</h3> <b>The ERS/ATS z-score classification of dysfunction discriminates COPD patients in progressively higher levels of mechanical–ventilatory impairment, activity-related dyspnoea and exercise intolerance</b>https://bit.ly/45wHANB
Monitoring melanoma patients on treatment reveals a distinct macrophage population driving targeted therapy resistance
Authors: Jelena Vasilevska, Phil Fang Cheng, Julia Lehmann, Egle Ramelyte, Julia Martínez Gómez, Florentia Dimitriou, Federica Sella, Daria Ferretti, Adrian Salas-Bastos, Whitney Shannon Jordaan, Mitchell Paul Levesque, Reinhard Dummer, Lukas Sommer
Journal: Cell Reports Medicine (2024)

Resistance to targeted therapy remains a major clinical challenge in melanoma. To uncover resistance mechanisms, we perform single-cell RNA sequencing on fine-needle aspirates from resistant and responding tumors of patients undergoing BRAFi/MEKi treatment. Among the genes most prominently expressed in resistant tumors is POSTN, predicted to signal to a macrophage population associated with targeted therapy resistance (TTR). Accordingly, tumors from patients with fast disease progression after therapy exhibit high POSTN expression levels and high numbers of TTR macrophages. POSTN polarizes human macrophages toward a TTR phenotype and promotes resistance to targeted therapy in a melanoma mouse model, which is associated with a phenotype change in intratumoral macrophages. Finally, polarized TTR macrophages directly protect human melanoma cells from MEKi-induced killing via CD44 receptor expression on melanoma cells. Thus, interfering with the protective activity of TTR macrophages may offer a strategy to overcome resistance to targeted therapy in melanoma.
Extreme overall mushroom genome expansion in Mycena s.s. irrespective of plant hosts or substrate specializations
Authors: Christoffer Bugge Harder, Shingo Miyauchi, Máté Virágh, Alan Kuo, Ella Thoen, Bill Andreopoulos, Dabao Lu, Inger Skrede, Elodie Drula, Bernard Henrissat, Emmanuelle Morin, Annegret Kohler, Kerrie Barry, Kurt LaButti, Asaf Salamov, Anna Lipzen, Zsolt Merényi, Botond Hegedüs, Petr Baldrian, Martina Stursova, Hedda Weitz, Andy Taylor, Maxim Koriabine, Emily Savage, Igor V. Grigoriev, László G. Nagy, Francis Martin, Håvard Kauserud
Journal: Cell Genomics (2024)

Mycena s.s. is a ubiquitous mushroom genus whose members degrade multiple dead plant substrates and opportunistically invade living plant roots. Having sequenced the nuclear genomes of 24 Mycena species, we find them to defy the expected patterns for fungi based on both their traditionally perceived saprotrophic ecology and substrate specializations. Mycena displayed massive genome expansions overall affecting all gene families, driven by novel gene family emergence, gene duplications, enlarged secretomes encoding polysaccharide degradation enzymes, transposable element (TE) proliferation, and horizontal gene transfers. Mainly due to TE proliferation, Arctic Mycena species display genomes of up to 502 Mbp (2-8× the temperate Mycena), the largest among mushroom-forming Agaricomycetes, indicating a possible evolutionary convergence to genomic expansions sometimes seen in Arctic plants. Overall, Mycena show highly unusual, varied mosaic-like genomic structures adaptable to multiple lifestyles, providing genomic illustration for the growing realization that fungal niche adaptations can be far more fluid than traditionally believed.
Evolutionary and biomedical implications of sex differences in the primate brain transcriptome
Authors: Alex R. DeCasien, Kenneth L. Chiou, Camille Testard, Arianne Mercer, Josué E. Negrón-Del Valle, Samuel E. Bauman Surratt, Olga González, Michala K. Stock, Angelina V. Ruiz-Lambides, Melween I. Martínez, Susan C. Antón, Christopher S. Walker, Jérôme Sallet, Melissa A. Wilson, Lauren J.N. Brent, Michael J. Montague, Chet C. Sherwood, Michael L. Platt, James P. Higham, Noah Snyder-Mackler
Journal: Cell Genomics (2024)

Humans exhibit sex differences in the prevalence of many neurodevelopmental disorders and neurodegenerative diseases. Here, we generated one of the largest multi-brain-region bulk transcriptional datasets for the rhesus macaque and characterized sex-biased gene expression patterns to investigate the translatability of this species for sex-biased neurological conditions. We identify patterns similar to those in humans, which are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and support the rhesus macaque model for the translational study of these conditions.
Advancing presurgical non-invasive molecular subgroup prediction in medulloblastoma using artificial intelligence and MRI signatures
Authors: Yan-Ran Joyce Wang, Pengcheng Wang, Zihan Yan, Quan Zhou, Fatma Gunturkun, Peng Li, Yanshen Hu, Wei Emma Wu, Kankan Zhao, Michael Zhang, Haoyi Lv, Lehao Fu, Jiajie Jin, Qing Du, Haoyu Wang, Kun Chen, Liangqiong Qu, Keldon Lin, Michael Iv, Hao Wang, Xiaoyan Sun, Hannes Vogel, Summer Han, Lu Tian, Feng Wu, Jian Gong
Journal: Cancer Cell (2024)
Proteobacteria impair anti-tumor immunity in the omentum by consuming arginine
Authors: Selene Meza-Perez, Mingyong Liu, Aaron Silva-Sanchez, Casey D. Morrow, Peter G. Eipers, Elliot J. Lefkowitz, Travis Ptacek, Christopher D. Scharer, Alexander F. Rosenberg, Dave D. Hill, Rebecca C. Arend, Michael J. Gray, Troy D. Randall
Journal: Cell Host & Microbe (2024)
Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer
Authors: Caicun Zhou, Chongyang Li, Libo Luo, Xin Li, Keyi Jia, Ning He, Shiqi Mao, Wanying Wang, Chuchu Shao, Xinyu Liu, Kan Huang, Yaxin Yu, Xinlei Cai, Yingxue Chen, Zican Dai, Wei Li, Jia Yu, Jiayu Li, Feng Shen, Zaiyong Wang, Feng He, Xing Sun, Rongfu Mao, Wei Shi, Jun Zhang, Tao Jiang, Zhe Zhang, Fei Li, Shengxiang Ren
Journal: Cancer Cell (2024)
Enhanced microbiota profiling in patients with quiescent Crohn’s disease through comparison with paired healthy first-degree relatives
Authors: Wanning Chen, Yichen Li, Wenxia Wang, Sheng Gao, Jun Hu, Bingjie Xiang, Dingfeng Wu, Na Jiao, Tao Xu, Min Zhi, Lixin Zhu, Ruixin Zhu
Journal: Cell Reports Medicine (2024)

Prior studies indicate no correlation between the gut microbes of healthy first-degree relatives (HFDRs) of patients with Crohn's disease (CD) and the development of CD. Here, we utilize HFDRs as controls to examine the microbiota and metabolome in individuals with active (CD-A) and quiescent (CD-R) CD, thereby minimizing the influence of genetic and environmental factors. When compared to non-relative controls, the use of HFDR controls identifies fewer differential taxa. Faecalibacterium, Dorea, and Fusicatenibacter are decreased in CD-R, independent of inflammation, and correlated with fecal short-chain fatty acids (SCFAs). Validation with a large multi-center cohort confirms decreased Faecalibacterium and other SCFA-producing genera in CD-R. Classification models based on these genera distinguish CD from healthy individuals and demonstrate superior diagnostic power than models constructed with markers identified using unrelated controls. Furthermore, these markers exhibited limited discriminatory capabilities for other diseases. Finally, our results are validated across multiple cohorts, underscoring their robustness and potential for diagnostic and therapeutic applications.
Heteroplasmy Is Rare in Plant Mitochondria Compared with Plastids despite Similar Mutation Rates
Authors: Marina Khachaturyan, Mario Santer, Thorsten B H Reusch, Tal Dagan
Journal: Molecular Biology and Evolution (2024)

Abstract Plant cells harbor two membrane-bound organelles containing their own genetic material—plastids and mitochondria. Although the two organelles coexist and coevolve within the same plant cells, they differ in genome copy number, intracellular organization, and mode of segregation. How these attributes affect the time to fixation or, conversely, loss of neutral alleles is currently unresolved. Here, we show that mitochondria and plastids share the same mutation rate, yet plastid alleles remain in a heteroplasmic state significantly longer compared with mitochondrial alleles. By analyzing genetic variants across populations of the marine flowering plant Zostera marina and simulating organelle allele dynamics, we examine the determinants of allele segregation and allele fixation. Our results suggest that the bottlenecks on the cell population, e.g. during branching or seeding, and stratification of the meristematic tissue are important determinants of mitochondrial allele dynamics. Furthermore, we suggest that the prolonged plastid allele dynamics are due to a yet unknown active plastid partition mechanism. The dissimilarity between plastid and mitochondrial novel allele fixation at different levels of organization may manifest in differences in adaptation processes. Our study uncovers fundamental principles of organelle population genetics that are essential for further investigations of long-term evolution and molecular dating of divergence events.
CMAPLE: efficient phylogenetic inference in the pandemic era
Authors: Nhan Ly-Trong, Chris Bielow, Nicola De Maio, Bui Quang Minh
Journal: Molecular Biology and Evolution (2024)

Abstract We have recently introduced MAPLE (MAximum Parsimonious Likelihood Estimation), a new pandemic-scale phylogenetic inference method exclusively designed for genomic epidemiology. In response to the need for enhancing MAPLE's performance and scalability, here we present two key components: (i) CMAPLE software, a highly optimized C++ reimplementation of MAPLE with many new features and advancements, and (ii) CMAPLE library, a suite of application programming interfaces to facilitate the integration of the CMAPLE algorithm into existing phylogenetic inference packages. Notably, we have successfully integrated CMAPLE into the widely used IQ-TREE 2 software, enabling its rapid adoption in the scientific community. These advancements serve as a vital step toward better preparedness for future pandemics, offering researchers powerful tools for large-scale pathogen genomic analysis.
An open‐label study of belumosudil, a selective ROCK2 inhibitor, as second or subsequent line of therapy for steroid‐dependent/steroid‐resistant chronic GVHD
Authors: Yoshihiro Inamoto, Koji Kato, Toshiro Kawakita, Yasushi Onishi, Ken‐ichi Matsuoka, Soichi Shiratori, Kazuhiro Ikegame, Nobuhiro Hiramoto, Masako Toyosaki, Yuta Katayama, Shun Murayama, Yuji Sasagawa, Yoshinobu Maeda, Kiyohiko Hatake, Takanori Teshima
Journal: American Journal of Hematology (2024)

Abstract Belumosudil mesylate is a selective Rho‐associated coiled‐coil kinase 2 inhibitor with immunomodulatory and antifibrosis effects. This multicenter, open‐label, single‐arm study evaluated belumosudil 200 mg once daily as second or subsequent line of therapy (LOT) in 21 Japanese patients ≥12 years of age with steroid‐dependent/steroid‐resistant chronic graft‐versus‐host disease (cGVHD). The primary endpoint of best overall response rate (ORR) at 24 weeks after enrollment of the last patient was 85.7% (95% confidence interval [CI]: 63.7–97.0), and the lower limit of the 95% CI exceeded the pre‐defined threshold of 25%. The Kaplan–Meier estimate of duration of response rate at 24 weeks was 75% (95% CI: 46–90); 13/18 responders (72.2%) had a sustained response for ≥20 weeks. The median time to response was 4.1 weeks (range 3.90–8.10); ORR was 47.6% at 4 weeks and 75.0% at 24 weeks; best ORR was 80% for joints/fascia, 66.7% for the mouth, and 54.5% for skin. Overall, 57.1% of patients had clinically meaningful symptom improvement at least once; the median duration of symptom improvement was 22.2 weeks (range 4.0–51.3). Corticosteroid dose reductions were recorded for 57.1% of patients. Median failure‐free and overall survival were not reached. Treatment‐emergent adverse events occurred in 85.7% of patients (most commonly diarrhea, 19.0%), of which 38.1% were drug‐related. There were no drug‐related discontinuations or deaths. In summary, belumosudil 200 mg once daily as second or subsequent LOT in Japanese patients with steroid‐dependent/steroid‐resistant cGVHD was effective, with no new safety concerns.
Maturation of germinal center B cells after influenza virus vaccination in humans
Authors: Katherine M. McIntire, Hailong Meng, Ting-Hui Lin, Wooseob Kim, Nina E. Moore, Julianna Han, Meagan McMahon, Meng Wang, Sameer Kumar Malladi, Bassem M. Mohammed, Julian Q. Zhou, Aaron J. Schmitz, Kenneth B. Hoehn, Juan Manuel Carreño, Temima Yellin, Teresa Suessen, William D. Middleton, Sharlene A. Teefey, Rachel M. Presti, Florian Krammer, Jackson S. Turner, Andrew B. Ward, Ian A. Wilson, Steven H. Kleinstein, Ali H. Ellebedy
Journal: The Journal of Experimental Medicine (2024)

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity and breadth to influenza hemagglutinin (HA) antigens compared with related GC clonotypes isolated earlier in the response. Structural studies of early and late GC-derived mAbs from one clonal lineage in complex with H1 and H5 HAs revealed an altered binding footprint. Our study shows that inducing sustained GC reactions after influenza vaccination in humans supports the maturation of responding B cells.
Proteasome inhibition for glioblastoma: Lessons learned and new opportunities
Authors: S John Liu, David R Raleigh, John F de Groot
Journal: Neuro-Oncology (2024)

Journal Article Accepted manuscript Proteasome inhibition for glioblastoma: lessons learned and new opportunities Get access S John Liu, S John Liu Department of Radiation Oncology and Neurosurgery, University of California, San Francisco Search for other works by this author on: Oxford Academic PubMed Google Scholar David R Raleigh, David R Raleigh Department of Radiation Oncology, Neurosurgery, and Pathology, University of California, San Francisco Search for other works by this author on: Oxford Academic PubMed Google Scholar John F de Groot John F de Groot Department of Neurosurgery, 400 Parnassus Ave, 8th Floor, University of California, San Francisco, San Francisco, CA Corresponding author: John F. de Groot, Department of Neurosurgery, 400 Parnassus Ave, 8th Floor, University of California, San Francisco , San Francisco, CA 94143, john.degroot@ucsf.edu, 415-353-2966 https://orcid.org/0000-0003-1454-6461 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae118, https://doi.org/10.1093/neuonc/noae118 Published: 27 June 2024 Article history Received: 13 June 2024 Published: 27 June 2024