tbuckley/cabot-search huggingface dataset:
Rapid Changes in Serum Testosterone in Men With Newly Diagnosed Type 2 Diabetes With Intensive Insulin and Metformin
Authors: Yun Hu, Bo Ding, Yun Shen, Reng-Na Yan, Feng-Fei Li, Rui Sun, Ting Jing, Kok-Onn Lee, Jian-Hua Ma
Journal: Diabetes Care (2021)

To investigate the effect of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM).
The Triple Aim Applied to Correctional Health Systems
Authors: Donald M. Berwick, Adam L. Beckman, Suhas Gondi
Journal: JAMA (2021)

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In adults hospitalized with COVID-19, the quick COVID-19 Severity Index predicted 24-h respiratory decompensation
Authors: Cody Dunne, Eddy Lang
Journal: Annals of Internal Medicine (2021)

Source CitationHaimovich AD, Ravindra NG, Stoytchev S, et al. Development and validation of the quick COVID-19 Severity Index: a prognostic tool for early clinical decompensation. Ann Emerg Med. 2020;76:442-53. https://pubmed.ncbi.nlm.nih.gov/33012378/AbstractClinical Impact RatingsEmergency Med: Hospitalists: Infectious Disease: Pulmonology:
Efficacy and Safety of Deferasirox in Chelation Naïve HbEβ Thalassemia Patients: Initial Experience from a Tertiary Centre of Eastern India
Authors: Debmalya Bhattacharyya, Ranadip Chowdhury, Soumita Choudhuri, Pramit Ghosh, Maitreyee Bhattacharyya
Journal: Blood (2017)
Elucidating cancer-vascular paracrine signaling using a human organotypic breast cancer cell extravasation model
Authors: Mouhita Humayun, Jose M. Ayuso, Raven A. Brenneke, María Virumbrales-Muñoz, Karina Lugo-Cintrón, Sheena Kerr, Suzanne M. Ponik, David J. Beebe
Journal: Biomaterials (2021)
COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses
Authors: Agnes Bonifacius, Sabine Tischer-Zimmermann, Anna C. Dragon, Daniel Gussarow, Alexander Vogel, Ulrike Krettek, Nina Gödecke, Mustafa Yilmaz, Anke R.M. Kraft, Marius M. Hoeper, Isabell Pink, Julius J. Schmidt, Yang Li, Tobias Welte, Britta Maecker-Kolhoff, Jörg Martens, Marc Moritz Berger, Corinna Lobenwein, Metodi V. Stankov, Markus Cornberg, Sascha David, Georg M.N. Behrens, Oliver Witzke, Rainer Blasczyk, Britta Eiz-Vesper
Journal: Immunity (2021)
Tocilizumab Prevents Progression of Early Systemic Sclerosis–Associated Interstitial Lung Disease
Authors: David Roofeh, Celia J. F. Lin, Jonathan Goldin, Grace Hyun Kim, Daniel E. Furst, Christopher P. Denton, Suiyuan Huang, Dinesh Khanna
Journal: Arthritis & Rheumatology (2021)

Tocilizumab (TCZ) has demonstrated lung function preservation in 2 randomized controlled trials in early systemic sclerosis (SSc). This effect has yet to be characterized in terms of radiographically evident quantitative lung involvement. We undertook this study to assess the impact of TCZ on lung function preservation in a post hoc analysis, stratifying treatment arms according to the degree of lung involvement.
Abstract 13154: Modulation of Stem Cell Niche and Stem Cell Migration Promotes Functional Angiogenesis by Enhancing Stem Cell Homing in Ischemic Rat Myocardium: A Novel Concept of Cell-free Regeneration Therapy
Authors: Nagako Sougawa, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Shigeo Masuda, Akima Harada, Yukiko Imanishi, Ryoko Sato-Nishiuchi, Kiyotoshi Sekiguchi, Yoshiki Sawa
Journal: Circulation (2015)

Background: The microenvironments composed of extracellular matrix (ECM) components and cytokines are considered to be involved in the decision of the stem cell fate and behavior. In addition, some cytokines induced by ONO1301 has been reported to enhance cell migration contributing to myocardial regeneration. In this study, we hypothesized that combined administration of cardiac specific ECM such as laminins and ONO1301 may enhance regeneration process by modulation of stem cell activity and homing. Methods and Results: In vitro study revealed that MSCs showed strong adhesion to laminin (LM) 511. ONO1301 promoted the production of several cytokines in smooth muscle cells, and it enhanced MSCs migration in vitro assay. To examine the therapeutic effect of ONO1301 combined with LM511, we transplanted ONO1301 or ONO1301 with LM511 (n=5-12) in a rat acute myocardial infarction model. Four weeks later, the number of PDGFRα- and CD90-positive cells tended to be higher in the combination (ONO1301 with LM511) group than in the ONO1301 alone group. Furthermore the gene expression of Sca-1 and c-kit was higher in the combination group than the control group (Sca-1, ONO1301 with LM511: 2.16- (p&lt;0.05), ONO1301 alone: 2.01-fold to the control, c-kit, ONO1301 with LM511: 2.75- (p&lt;0.05), ONO1301 alone: 1.45-fold to the control). Histological examination revealed that the number of ILB4 (endothelial cell marker) positive cells was significantly higher in the combination group than in the ONO1301 group (ONO1301 with LM511: 521±68 cells/mm 2 , ONO1301 alone: 281±10 cells/mm 2 , control: 195±29 cells/mm 2 ; p&lt;0.05). Moreover, the number of CD31 (endothelial cell marker) and SMA (smooth muscle cell marker) double positive cell was significantly higher in the combination group compared with the control group (ONO1301 with LM511: 616±44 cells/mm 2 , control: 226±60 cells/mm 2 ; p&lt;0.05). Real time PCR analysis revealed that SDF-1, PGF, FGF2 and HGF were higher in the combination group. Moreover, infarct size tended to be smaller in the combination group than in the ONO1301 group. Conclusion: The cell free regeneration therapy using both ONO1301 and LM511 may contribute to enhanced stem cell homing to implanted site, leading to improve functional angiogenesis in rat ischemic heart.
A wrist injury
Authors: Kashif Ahmad, Girish Vashista
Journal: BMJ (2021)

A man in his 20s presented with deformity and severe pain in his left shoulder and wrist after a mid-air collision with a motocross bike. The patient’s torso had collided with another rider’s bike, causing him to land on his left upper chest and arm. After Advanced Trauma Life Support (ATLS) assessment the patient was found to be stable and resuscitation was not needed. Two isolated injuries were identified: a closed displaced fracture of the left clavicle and a deformed left wrist with no distal neurovascular compromise. Orthogonal radiography (anteroposterior and lateral views) of the left wrist was performed (figs 1 and 2).



Fig 1 
Anteroposterior radiograph of left wrist





Fig 2 
Lateral radiograph of left wrist



The patient was …
Long COVID: tackling a multifaceted condition requires a multidisciplinary approach
Authors: Alice Norton, Piero Olliaro, Louise Sigfrid, Gail Carson, Giuseppe Paparella, Claire Hastie, Charu Kaushic, Geneviève Boily-Larouche, Jake C Suett, Margaret O'Hara
Journal: The Lancet Infectious Diseases (2021)

In their Comment,1 Dana Yelin and colleagues highlight the persistent, heterogeneous, and recurring symptoms of long COVID. A Lancet Editorial2 asks for better research and care to avoid years of struggle for individuals with long COVID. We write following an international, multi-stakeholder forum, in which peoples' voices were central, to expand the call to action and to identify how we can prevent long COVID from becoming the long-lasting legacy of COVID-19.
The S100 calcium-binding protein A11 promotes hepatic steatosis through RAGE-mediated AKT-mTOR signaling
Authors: Fei Teng, Jingjing Jiang, Jinhua Zhang, Youwen Yuan, Kangli Li, Bing Zhou, Xuan Zhou, Wenhui Liu, Peizhen Zhang, Deying Liu, Minghua Zheng, Yan Lu, Huijie Zhang
Journal: Metabolism (2021)
TGFβ drives NK cell metabolic dysfunction in human metastatic breast cancer
Authors: Karen Slattery, Elena Woods, Vanessa Zaiatz-Bittencourt, Sam Marks, Sonya Chew, Michael Conroy, Caitriona Goggin, Colm MacEochagain, John Kennedy, Sophie Lucas, David K Finlay, Clair M Gardiner
Journal: Journal for ImmunoTherapy of Cancer (2021)

Natural killer (NK) cells provide important immune protection from cancer and are a key requirement for particular immunotherapies. There is accumulating evidence that NK cells become dysfunctional during cancer. Overcoming NK cell exhaustion would be an important step to allow them to function optimally in a range of NK cell therapies, including those that depend on autologos circulating NK cells. We have previously demonstrated that NK cells undergo a normal metabolic reprogramming in response to cytokine activation and that this is required for optimal function. The objective of this work was to investigate if cellular metabolism of circulating NK cells is dysregulated in patients with metastatic breast cancer and if so, to gain insights into potential mechanisms underpinning this. Such discoveries would provide important insights into how to unleash the full activity of NK cells for maximum immunotherapy output.Single-cell analysis, metabolic flux and confocal analysis of NK cells from patients with metastatic breast cancer and healthy controls RESULTS: In addition to reduced interferon-γ production and cytotoxicity, peripheral blood NK cells from patients had clear metabolic deficits including reduced glycolysis and oxidative phosphorylation. There were also distinct morphologically alterations in the mitochondria with increased mitochondrial fragmentation observed. Transforminggrowth factor-β (TGFβ) was identified as a key driver of this phenotype as blocking its activity reversed many metabolic and functional readouts. Expression of glycoprotein-A repetitions predominant (GARP) and latency associated peptide (LAP), which are involved with a novel TGFβ processing pathway, was increased on NK cells from some patients. Blocking the GARP-TGFβ axis recapitulated the effects of TGFβ neutralization, highlighting GARP as a novel NK cell immunotherapy target for the first time.TGFβ contributes to metabolic dysfunction of circulating NK cells in patients with metastatic breast cancer. Blocking TGFβ and/or GARP can restore NK cell metabolism and function and is an important target for improving NK cell-based immunotherapies.
PINK1-Mediated Inhibition of EGFR Dimerization and Activation Impedes EGFR-Driven Lung Tumorigenesis
Authors: Emily Pei-Ying Lin, Bo-Tsang Huang, Wei-Yun Lai, Yi-Ting Tseng, Shuenn-Chen Yang, Hao-Cheng Kuo, Pan-Chyr Yang
Journal: Cancer Research (2021)

EGFR is established as a driver of lung cancer, yet the regulatory machinery underlying its oncogenic activity is not fully understood. PTEN-induced kinase 1 (PINK1) kinase is a key player in mitochondrial quality control, although its role in lung cancer and EGFR regulation is unclear. In this study, we show that PINK1 physically directly interacts with EGFR via the PINK1 C-terminal domain (PINK1-CTD) and the EGFR tyrosine kinase domain. This interaction constituted an endogenous steric hindrance to receptor dimerization and inhibited EGFR-mediated lung carcinogenesis. Depletion of PINK1 from lung cancer cells promoted EGFR dimerization, receptor activation, EGFR downstream signaling, and tumor growth. In contrast, overexpression of PINK1 or PINK1-CTD suppressed EGFR dimerization, activation, downstream signaling, and tumor growth. These findings identify key elements in the EGFR regulatory cascade and illustrate a new direction for the development of anti-EGFR therapeutics, suggesting translational potential of the PINK1-CTD in lung cancer. SIGNIFICANCE: This study identifies PINK1 as a critical tumor suppressor that impedes EGFR dimerization and highlights PINK1-CTD as a potential therapeutic agent in EGFR-driven lung cancer.
Tumor Mutational Burden and Mismatch Repair Deficiency Discordance as a Mechanism of Immunotherapy Resistance
Authors: Agata A. Bielska, Walid K. Chatila, Henry Walch, Nikolaus Schultz, Zsofia K. Stadler, Jinru Shia, Diane Reidy-Lagunes, Rona Yaeger
Journal: Journal of the National Comprehensive Cancer Network (2021)

Lynch syndrome is a heritable cancer syndrome caused by a heterozygous germline mutation in DNA mismatch repair (MMR) genes. MMR-deficient (dMMR) tumors are particularly sensitive to immune checkpoint inhibitors, an effect attributed to the higher mutation rate in these cancers. However, approximately 15% to 30% of patients with dMMR cancers do not respond to immunotherapy. This report describes 3 patients with Lynch syndrome who each had 2 primary malignancies: 1 with dMMR and a high tumor mutational burden (TMB), and 1 with dMMR but, unexpectedly, a low TMB. Two of these patients received immunotherapy for their TMB-low tumors but experienced no response. We have found that not all Lynch-associated dMMR tumors have a high TMB and propose that tumors with dMMR and TMB discordance may be resistant to immunotherapy. The possibility of dMMR/TMB discordance should be considered, particularly in less-typical Lynch cancers, in which TMB evaluation could guide the use of immune checkpoint inhibitors.
Caution advised regarding lung recruitment before surfactant – Authors’ reply
Authors: Giovanni Vento, M L Ventura, R Pastorino, A H van Kaam, V Carnielli, F Cools, C Dani, F Mosca, G Polglase, P Tagliabue, L Boni, F Cota, M Tana, C Tirone, C Aurilia, A Lio, S Cost, V D'Andrea, M Lucente, G Nigro, L Giordano, V Roma, P Villani, F P Fusco, V Fasolato, M R Colnaghi, P G Matassa, V Vendettuoli, C Poggi, A Del Vecchi, F Petrillo, P Betta, C Mattia, G Garani, A Solinas, E Gitto, V Salvo, G Gargano, E Balestri, F Sandri, G Mescoli, S Martinelli, L Ilardi, E Ciarmoli, S Di Fabio, E Maranella, C Grassia, G Ausanio, V Rossi, A Motta, L G Tina, K Maiolo, S Nobile, H Messner, A Staffler, F Ferrero, I Stasi, L Pieragostini, I Mondello, C Haass, C Consigli, S Vedovato, A Grison, G Maffei, G Presta, R Perniola, M Vitaliti, M P Re, M De Curtis, V Cardilli, P Lago, F Tormena, L Orfeo, C Gizzi, L Massenzi, D Gazzolo, M C M Strozzi, R Bottino, F Pontiggia, A Berardi, I Guidotti, C Cacace, V Meli, L Quartulli, A Scorrano, A Casati, L Grappone, J J Pillow
Journal: The Lancet Respiratory Medicine (2021)
Moving towards a better identification and management of frailty in ICU survivors
Authors: Zafeiris Louvaris, Daniel Langer
Journal: Thorax (2021)

Frailty is a geriatric syndrome that is defined as ‘a physiologic state of increased vulnerability to stressors due to decreased physiologic reserves, and dysregulation, of multiple physiologic systems’.1 Frailty syndrome partly overlaps with sarcopenia, the latter encompass states of loss of muscle mass and function related to ageing alone.2 Frail patients present with an increased burden of symptoms including muscle weakness, excessive muscle fatigue during daily activities and reduced tolerance to medical and surgical interventions.3 

Along these lines, studies have demonstrated that frailty is a common phenomenon observed in approximately 30% of adult intensive care unit (ICU) admissions.4 Patients with pre-ICU frailty have a higher prevalence of in-hospital mortality, long-term morbidity and mortality and poorer quality of life after hospital discharge compared with non-frail ICU patients.4 Nevertheless, limited knowledge exists as to whether post-ICU frailty impacts on long-term mortality and recovery to activities of daily living after hospital discharge.

In this issue of Thorax , Baldwin et al 5 examined 185 elderly (>65 years old), acute respiratory failure (ARF) survivors to identify distinct frailty subtypes. Authors applied a novel statistical approach (ie, latent class analysis ) for assessing whether different frailty phenotype domains5 (ie, grip strength, gait-speed, feelings of exhaustion, weight loss and physical activity) and differences in cognitive …
Gut <i>Bacteroides</i> species in health and disease
Authors: Hassan Zafar, Milton H. Saier
Journal: Gut Microbes (2021)

The functional diversity of the mammalian intestinal microbiome far exceeds that of the host organism, and microbial genes contribute substantially to the well-being of the host. However, beneficial gut organisms can also be pathogenic when present in the gut or other locations in the body. Among dominant beneficial bacteria are several species of
Therapeutic Targeting of Nemo-like Kinase in Primary and Acquired Endocrine-resistant Breast Cancer
Authors: Xian Wang, Jamunarani Veeraraghavan, Chia-Chia Liu, Xixi Cao, Lanfang Qin, Jin-Ah Kim, Ying Tan, Suet Kee Loo, Yiheng Hu, Ling Lin, Sanghoon Lee, Martin J. Shea, Tamika Mitchell, Shunqiang Li, Matthew J. Ellis, Susan G. Hilsenbeck, Rachel Schiff, Xiao-Song Wang
Journal: Clinical Cancer Research (2021)

Endocrine resistance remains a major clinical challenge in estrogen receptor (ER)-positive breast cancer. Despite the encouraging results from clinical trials for the drugs targeting known survival signaling, relapse is still inevitable. There is an unmet need to discover new drug targets in the unknown escape pathways. Here, we report Nemo-like kinase (NLK) as a new actionable kinase target that endows previously uncharacterized survival signaling in endocrine-resistant breast cancer.The effects of NLK inhibition on the viability of endocrine-resistant breast cancer cell lines were examined by MTS assay. The effect of VX-702 on NLK activity was verified by kinase assay. The modulation of ER and its coactivator, SRC-3, by NLK was examined by immunoprecipitation, kinase assay, luciferase assay, and RNA sequencing. The therapeutic effects of VX-702 and everolimus were tested on cell line- and patient-derived xenograft (PDX) tumor models.NLK overexpression endows reduced endocrine responsiveness and is associated with worse outcome of patients treated with tamoxifen. Mechanistically, NLK may function, at least in part, via enhancing the phosphorylation of ERα and its key coactivator, SRC-3, to modulate ERα transcriptional activity. Through interrogation of a kinase profiling database, we uncovered and verified a highly selective dual p38/NLK inhibitor, VX-702. Coadministration of VX-702 with the mTOR inhibitor, everolimus, demonstrated a significant therapeutic effect in cell line-derived xenograft and PDX tumor models of acquired or de novo endocrine resistance.Together, this study reveals the potential of therapeutic modulation of NLK for the management of the endocrine-resistant breast cancers with active NLK signaling.
Corticosteroids in COVID-19: one size does not fit all
Authors: Athena Gogali, Chris Kyriakopoulos, Konstantinos Kostikas
Journal: European Respiratory Journal (2021)

<b>Organising pneumonia and acute fibrinous and organising pneumonia have been reported as the predominant patterns in pathological samples from COVID-19 patients. Critically ill COVID-19 patients may benefit even more from higher corticosteroid doses.</b>https://bit.ly/3timqPM
A Survey of Respiratory Symptoms Reported in Patients Following Hospitalization with COVID-19 Infection
Authors: Eevar B. Rossavik, Zain Iftikhar, Iftikhar Hussain
Journal: Journal of Allergy and Clinical Immunology (2021)

The coronavirus disease 2019 (COVID-19) pandemic has led to a global health emergency. It is an airborne, respiratory infection with multi-systemic involvement, notably in the upper and lower airways. Clinical manifestations range from asymptomatic to respiratory failure requiring advanced airway with mechanical ventilation - and even death. There is limited information about respiratory symptoms after treatment for the disease after hospital discharge. An Institutional Review Board (IRB) approved phone survey was conducted for patients hospitalized and discharged with COVID-19 from a local tertiary center. A list was generated of COVID-19 patients diagnosed by RT-PCR at the same facility March to August 2020. Phone numbers were obtained from patient demographics. Of a list of 232 individuals, 42 patients responded. Average age at diagnosis was 59.2 years (ranging 7 to 87 years). Patients or their caretakers were asked if additional therapy/treatment was needed in addition to a list of symptoms that were caused/worsened by COVID-19 infection within 6 months post-discharge. 38.1% of patients required some form of additional therapy after discharge. Patients reported: fatigue (52.4%), changes in activities of daily living (52.4%), shortness of breath (47.6%), decreased smell/taste (42.9%), increased mucus production (38.1%), nasal congestion (28.6%), rhinorrhea (28.6%), cough (26.2%), chest tightness (23.8%), sneezing (19.0%), wheezing (16.7%), and sinus pain/pressure (11.9%). In the 6 months following hospital discharge for a subset of patients with COVID-19 infection, residual shortness of breath and decreased smell/taste, in addition to fatigue and changes in activities of daily living, were more often reported than other respiratory symptoms.
Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses
Authors: Ying Kai Chan, Sean K. Wang, Colin J. Chu, David A. Copland, Alexander J. Letizia, Helena Costa Verdera, Jessica J. Chiang, Meher Sethi, May K. Wang, William J. Neidermyer, Yingleong Chan, Elaine T. Lim, Amanda R. Graveline, Melinda Sanchez, Ryan F. Boyd, Thomas S. Vihtelic, Rolando Gian Carlo O. Inciong, Jared M. Slain, Priscilla J. Alphonse, Yunlu Xue, Lindsey R. Robinson-McCarthy, Jenny M. Tam, Maha H. Jabbar, Bhubanananda Sahu, Janelle F. Adeniran, Manish Muhuri, Phillip W. L. Tai, Jun Xie, Tyler B. Krause, Andyna Vernet, Matthew Pezone, Ru Xiao, Tina Liu, Wei Wang, Henry J. Kaplan, Guangping Gao, Andrew D. Dick, Federico Mingozzi, Maureen A. McCall, Constance L. Cepko, George M. Church
Journal: Science Translational Medicine (2021)

Incorporating TLR9-inhibitory sequences in the AAV vector genome inhibits immunogenicity and enhances transgene expression in multiple animal models.