tbuckley/cabot-search huggingface dataset:
Synaptic input to brain tumors: clinical implications
Authors: Varun Venkataramani, Dimitar Ivanov Tanev, Thomas Kuner, Wolfgang Wick, Frank Winkler
Journal: Neuro-Oncology (2020)

Abstract The recent discovery of synaptic connections between neurons and brain tumor cells fundamentally challenges our understanding of gliomas and brain metastases and shows how these tumors can integrate into complex neuronal circuits. Here, we provide an overview of glutamatergic neuron-to-brain tumor synaptic communication (NBTSC) and explore novel therapeutic avenues. First, we summarize current concepts of direct synaptic interactions between presynaptic neurons and postsynaptic glioma cells, and indirect perisynaptic input to metastatic breast cancer cells. We explain how these novel structures drive brain tumor growth and invasion. Second, a vicious cycle of enhanced neuronal activity, including tumor-related epilepsy, and glioma progression is described. Finally, we discuss which future avenues to target NBTSC appear most promising. All in all, further characterization of NBTSC and the exploration of NBTSC-inhibiting therapies have the potential to reveal critical vulnerabilities of yet incurable brain tumors.
The deubiquitinase USP25 supports colonic inflammation and bacterial infection and promotes colorectal cancer
Authors: Xiao-Meng Wang, Ci Yang, Yin Zhao, Zhi-Gao Xu, Wei Yang, Peng Wang, Dandan Lin, Bin Xiong, Jing-Yuan Fang, Chen Dong, Bo Zhong
Journal: Nature Cancer (2020)
Association Between Changes in Timing of Spring Onset and Asthma Hospitalization in Maryland
Authors: Amir Sapkota, Yan Dong, Linze Li, Ghassem Asrar, Yuyu Zhou, Xuecao Li, Frances Coates, Adam J. Spanier, Jonathan Matz, Leonard Bielory, Allison G. Breitenother, Clifford Mitchell, Chengsheng Jiang
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Ongoing climate change is affecting the health of communities across the globe. While direct consequences, including morbidity and mortality tied to increases in the frequency of extreme weather events, have received significant attention, indirect health effects, particularly those associated with climate change–driven disruptions in ecosystems, are less understood. <h3>Objective</h3> To investigate how ongoing changes in the timing of spring onset related to climate change are associated with rates of asthma hospitalization in Maryland. <h3>Design, Setting, and Participants</h3> This cross-sectional study of 29 257 patients with asthma used general additive (quasi Poisson) and mixed-effect (negative binomial) models to investigate the association between changes in the timing of spring onset, detected using satellite observations, and the risk of asthma hospitalization in Maryland from 2001 to 2012. Data analysis was conducted from January 2016 to March 2019. <h3>Exposures</h3> Phenology data, derived from the National Aeronautics and Space Administration’s Moderate Resolution Imaging Spectroradiometer, were used to calculate location-specific median dates for start of season from 2001 to 2012. How the start of season for a given year and location deviated from the long-term average was calculated and categorized as very early, early, normal, or late. <h3>Main Outcomes and Measures</h3> Daily asthma hospitalization in Maryland during the spring season (ie, March to May). <h3>Results</h3> There were 108 358 total asthma hospitalizations during the study period, of which 29 257 (27.0%; 14 379 [49.1%] non-Hispanic black patients; 17 877 [61.1%] women) took place during springtime. In the unadjusted model, very early (incident rate ratio [IRR], 1.17; 95% CI, 1.07-1.28) and late (IRR, 1.07; 95% CI, 1.00-1.15) onset of spring were associated with increased risk of asthma hospitalization. When the analysis was adjusted for extreme heat events and concentrations of particulate matter with an aerodynamic diameter less than 2.5 μm, the risk remained significant for very early spring onset (IRR, 1.10; 95% CI, 1.02-1.20) but not for late spring onset (IRR, 1.03; 95% CI, 0.97-1.11). <h3>Conclusions and Relevance</h3> These results suggest that ongoing changes in the timing of spring onset, which are related to climate variability and change, are associated with asthma hospitalization. Given the high burden of allergic diseases and the number of individuals sensitized to tree pollen, these findings serve as a wake-up call to public health and medical communities regarding the need to anticipate and adapt to the ongoing changes in the timing and severity of the spring allergy season.
Covid-19: How does local lockdown work, and is it effective?
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: How does local lockdown work, and is it effective?England has announced its first local lockdown in response to covid-19, just as it begins to ease national restrictions.But will it work-and is this the first of many? Elisabeth MahaseLeicester, a city in England's East Midlands, has been placed under local lockdown after it was found to have three times more covid-19 cases than the next highest city. 1 The area accounted for around 10% of all positive cases in the country in the week leading up to the announcement on 29 June, with six to 10 hospital admissions a day, compared with around one at other NHS trusts.
Rationale and significance of patient selection in awake prone positioning for COVID-19 pneumonia
Authors: Ching-Feng Huang, Chee Kiang Tay, Ya-Fang Zhuang, Jiaxuan Liu, Duu Wen Sewa
Journal: European Respiratory Journal (2020)

<b>COVID-19 is increasingly recognised to manifest phenotypic diversity in clinical presentation, severity and trajectory. As such, treatment, e.g. awake prone positioning, should be personalised and guided by the primary pathophysiology and immunopathology.</b>https://bit.ly/2ZneHlF
Urgent Issues Facing Immigrant Physicians in the United States in the COVID-19 Era
Authors: Vivekanand Tiwari, Abhishek Bhardwaj, Bhavin Sonani, Atul C. Mehta
Journal: Annals of Internal Medicine (2020)

June 2020, the United States has endured more than 2.3 million cases of coronavirus disease 2019 (COVID-19) and 121 117 deaths (1).Available resources are stretched thin, and health care workers are overwhelmed.The COVID-19 pandemic has exposed vulnerabilities of the U.S. health care system beyond anyone's imagination.As we witness this disease ravage country after country, killing hundreds of thousands of people worldwide, doctors, nurses, and other health care professionals involved in taking care of COVID-19 patients directly place their own lives and the lives of their family members at risk.The most recent data from the Centers for Disease Control and Prevention show 84 557 cases and 469 deaths among health care professionals (1).Among health care workers in the United States, 1
Miltirone induces cell death in hepatocellular carcinoma cell through GSDME-dependent pyroptosis
Authors: Xiaowei Zhang, Ping Zhang, Lin An, Ningyuan Sun, Liying Peng, Weiwei Tang, Dingyuan Ma, Jun Chen
Journal: Acta Pharmaceutica Sinica B (2020)

Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root of Salvia miltiorrhiza Bunge, has been shown to possess anti-cancer activities. Here, we found that miltirone inhibited the cell viability of either HepG2 or Hepa1-6 cells, and induced the proteolytic cleavage of gasdermin E (GSDME) in each hepatocellular carcinoma (HCC) cell line, with concomitant cleavage of caspase 3. Knocking out GSDME switched miltirone-induced cell death from pyroptosis to apoptosis. Additionally, the induction effects of miltirone on GSDME-dependent pyroptosis were attenuated by siRNA-mediated caspase three silencing and the specific caspase three inhibitor Z-DEVD-FMK, respectively. Miltirone effectively elicited intracellular accumulation of reactive oxygen species (ROS), and suppressed phosphorylation of mitogen-activated and extracellular signal-regulated kinase (MEK) and extracellular regulated protein kinases 1/2 (ERK1/2) for pyroptosis induction. Moreover, miltirone significantly inhibited tumor growth and induced pyroptosis in the Hepa1-6 mouse HCC syngeneic model. These results provide a new insight that miltirone is a potential therapeutic agent for the treatment of HCC via GSDME-dependent pyroptosis.
Mutations in the iron-sulfur cluster biogenesis protein HSCB cause congenital sideroblastic anemia
Authors: Andrew Crispin, Chaoshe Guo, Caiyong Chen, Dean R. Campagna, Paul J. Schmidt, Daniel Lichtenstein, Chang Cao, Anoop K. Sendamarai, Gordon J. Hildick-Smith, Nicholas C. Huston, Jeanne Boudreaux, Sylvia S. Bottomley, Matthew M. Heeney, Barry H. Paw, Mark D. Fleming, Sarah Ducamp
Journal: Journal of Clinical Investigation (2020)

The congenital sideroblastic anemias (CSAs) can be caused by primary defects in mitochondrial iron-sulfur (Fe-S) cluster biogenesis. HSCB (heat shock cognate B), which encodes a mitochondrial cochaperone, also known as HSC20 (heat shock cognate protein 20), is the partner of mitochondrial heat shock protein A9 (HSPA9). Together with glutaredoxin 5 (GLRX5), HSCB and HSPA9 facilitate the transfer of nascent 2-iron, 2-sulfur clusters to recipient mitochondrial proteins. Mutations in both HSPA9 and GLRX5 have previously been associated with CSA. Therefore, we hypothesized that mutations in HSCB could also cause CSA. We screened patients with genetically undefined CSA and identified a frameshift mutation and a rare promoter variant in HSCB in a female patient with non-syndromic CSA. We found that HSCB expression was decreased in patient-derived fibroblasts and K562 erythroleukemia cells engineered to have the patient-specific promoter variant. Furthermore, gene knockdown and deletion experiments performed in K562 cells, zebrafish, and mice demonstrate that loss of HSCB results in impaired Fe-S cluster biogenesis, a defect in RBC hemoglobinization, and the development of siderocytes and more broadly perturbs hematopoiesis in vivo. These results further affirm the involvement of Fe-S cluster biogenesis in erythropoiesis and hematopoiesis and define HSCB as a CSA gene.
Asymptomatic SARS-CoV-2 infection in Belgian long-term care facilities
Authors: Ana Hoxha, Chloe Wyndham-Thomas, Sofieke Klamer, Dominique Dubourg, Melissa Vermeulen, Naima Hammami, Laura Cornelissen
Journal: The Lancet Infectious Diseases (2020)

asymptomatic carriers of the virus could represent an important driver of transmission.To limit the spread of SARS-CoV-2 in closed residential facilities, we iterate the importance of widely applying extensive infection prevention and control measures as long as the epidemic is ongoing.We declare no competing interests.
Nanotherapy delivery of c-myc inhibitor targets Protumor Macrophages and preserves Antitumor Macrophages in Breast Cancer
Authors: Alison K. Esser, Michael H. Ross, Francesca Fontana, Xinming Su, Ariel Gabay, Gregory C. Fox, Yalin Xu, Jingyu Xiang, Anne H. Schmieder, Xiaoxia Yang, Grace Cui, Michael Scott, Samuel Achilefu, Jay Chauhan, Steven Fletcher, Gregory M. Lanza, Katherine N. Weilbaecher
Journal: Theranostics (2020)

Tumor-associated macrophages (TAMs) enhance tumor growth in mice and are correlated with a worse prognosis for breast cancer patients. While early therapies sought to deplete all macrophages, current therapeutics aim to reprogram pro-tumor macrophages (M2) and preserve those necessary for anti-tumor immune responses (M1). Recent studies have shown that c-MYC (MYC) is induced in M2 macrophages in vitro and in vivo where it regulates the expression of tumor-promoting genes. In a myeloid lineage MYC KO mouse model, MYC had important roles in macrophage maturation and function leading to reduced tumor growth. We therefore hypothesized that targeted delivery of a MYC inhibitor to established M2 TAMs could reduce polarization toward an M2 phenotype in breast cancer models. Methods: In this study, we developed a MYC inhibitor prodrug (MI3-PD) for encapsulation within perfluorocarbon nanoparticles, which can deliver drugs directly to the cytosol of the target cell through a phagocytosis independent mechanism. We have previously shown that M2-like TAMs express significant levels of the vitronectin receptor, integrin β3, and in vivo targeting and therapeutic potential was evaluated using αvβ3 integrin targeted rhodamine-labeled nanoparticles (NP) or integrin αvβ3-MI3-PD nanoparticles. Results: We observed that rhodamine, delivered by αvβ3-rhodamine NP, was incorporated into M2 tumor promoting macrophages through both phagocytosis-independent and dependent mechanisms, while NP uptake in tumor suppressing M1 macrophages was almost exclusively through phagocytosis. In a mouse model of breast cancer (4T1-GFP-FL), M2-like TAMs were significantly reduced with αvβ3-MI3-PD NP treatment. To validate this effect was independent of drug delivery to tumor cells and was specific to the MYC inhibitor, mice with integrin β3 knock out tumors (PyMT-Bo1 β3KO) were treated with αvβ3-NP or αvβ3-MI3-PD NP. M2 macrophages were significantly reduced with αvβ3-MI3-PD nanoparticle therapy but not αvβ3-NP treatment. Conclusion: These data suggest αvβ3-NP-mediated drug delivery of a c-MYC inhibitor can reduce protumor M2-like macrophages while preserving antitumor M1-like macrophages in breast cancer.
Risk of Depression in the Adolescent and Adult Offspring of Mothers With Perinatal Depression
Authors: Vaishali Tirumalaraju, Robert Suchting, Jonathan Evans, Laura Goetzl, Jerrie Refuerzo, Alexander Neumann, Deepa Anand, Rekha Ravikumar, Charles E. Green, Philip J. Cowen, Sudhakar Selvaraj
Journal: JAMA Network Open (2020)

Maternal depression during pregnancy is associated with emotional and behavioral difficulties of offspring during childhood that can increase the risk of depression in adolescence and adulthood.To investigate the association between perinatal maternal depression and an increased long-term risk of depression in their adolescent and adult offspring.A systematic search of the electronic databases of PubMed and PsycINFO was conducted from May 2019 to June 2019.A total of 6309 articles were identified, of which 88 articles were extracted for full-text review by 2 reviewers. Only articles reporting data from prospective longitudinal studies that assessed maternal depression during antenatal and/or postnatal periods and resulting offspring 12 years or older with measures of established psychometric properties were included. Exclusion criteria consisted of all other study designs, mothers with other medical and psychiatric comorbidities, and offspring younger than 12 years.Data were extracted by 2 independent reviewers, and discrepancies were mediated by an expert third reviewer. Meta-analysis was performed using Bayesian statistical inference and reported using Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline. The association of depression timing with the sex of offspring was explored using metaregression.Offspring depression was evaluated using standardized depression scales or clinical interviews.Six studies with a total of 15 584 mother-child dyads were included in the meta-analysis, which found the offspring of mothers who experienced perinatal depression to have increased odds of depression (odds ratio [OR], 1.70; 95% credible interval [CrI], 1.60-2.65; posterior probability [PP] [OR >1], 98.6%). Although metaregression found no evidence for an overall association between perinatal depression timing and offspring depression (antenatal vs postnatal, PP [OR >1] = 53.8%), subgroup analyses showed slightly higher pooled odds for the antenatal studies (OR, 1.78; 95% CrI, 0.93-3.33; PP [OR >1] = 96.2%) than for the postnatal studies (OR, 1.66; 95% CrI, 0.65-3.84; PP [OR >1] = 88.0%). Female adolescent offspring recorded higher rates of depression in metaregression analyses, such that a 1% increase in the percentage of female (relative to male) offspring was associated with a 6% increase in the odds of offspring depression (OR, 1.06; 95% CrI, 0.99-1.14; τ2 = 0.31).In this study, maternal perinatal depression, especially antenatal depression, was associated with the risk of depression in adolescence and adulthood. More research into the mechanisms of depression risk transmission and assessments of postinterventional risk reduction could aid in the development of future strategies to tackle depressive disorders in pregnancy.
Unusual Case of an Exophytic Leiomyoma of Rectum Mimicking Malignancy on 18F-FDG PET/CT
Authors: Chongjiao Li, Yueli Tian, Ying Shen, Bing Wen, Yong He
Journal: Clinical Nuclear Medicine (2020)

Rectal leiomyoma is an exceedingly rare benign lesion. We here report a case with extraluminal leiomyoma of the middle and lower parts of the rectum showing aberrant hypermetabolism on F-FDG PET/CT in a 54-year-old man.
Gambling: Academics call for statutory levy to reduce harm
Authors: Jacqui Wise
Journal: BMJ (2020)

More than 50 academic scientists have called for a statutory levy on gambling firms to bring about reductions in gambling harms, warning that the current voluntary system gives the industry too much influence on how the money is spent.

On 17 June the five largest members of the UK gambling industry’s representative organisation the Betting and Gaming Council announced that they will give £100m (€110m; $125m) to the charity GambleAware to improve treatment services for people with gambling problems.1

This funding was first promised on 2 August 2019 and was due to be given to the charity Action Against Gambling Harms, founded by the Conservative peer Peter Gummer. But in an open letter to the culture minister, Oliver Dowden, and the health secretary …
NCCN Guidelines Insights: Rectal Cancer, Version 6.2020
Authors: Al B. Benson, Alan P. Venook, Mahmoud M. Al-Hawary, Mustafa A. Arain, Yi-Jen Chen, Kristen K. Ciombor, Stacey Cohen, Harry S. Cooper, Dustin Deming, Ignacio Garrido-Laguna, Jean L. Grem, Andrew Gunn, Sarah Hoffe, Joleen Hubbard, Steven Hunt, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Michael J. Overman, Aparna Parikh, Hitendra Patel, Katrina Pedersen, Leonard Saltz, Charles Schneider, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Alyse Johnson-Chilla, Lisa A. Gurski
Journal: Journal of the National Comprehensive Cancer Network (2020)

The NCCN Guidelines for Rectal Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with rectal cancer. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines. These updates include clarifying the definition of rectum and differentiating the rectum from the sigmoid colon; the total neoadjuvant therapy approach for localized rectal cancer; and biomarker-targeted therapy for metastatic colorectal cancer, with a focus on new treatment options for patients with BRAF V600E- or HER2 amplification-positive disease.
Apgar Score and Risk of Neonatal Death among Preterm Infants
Authors: Sven Cnattingius, Stefan Johansson, Neda Razaz
Journal: New England Journal of Medicine (2020)

Gestational age is the major determinant of neonatal death (death within the first 28 days of life) in preterm infants. The joint effect of gestational age and Apgar score on the risk of neonatal death is unknown.
Engineering Circulating Tumor Cells as Novel Cancer Theranostics
Authors: Katie M Parkins, Veronica P Dubois, John J Kelly, Yuanxin Chen, Natasha N Knier, Paula J Foster, John A Ronald
Journal: Theranostics (2020)

New ways to target and treat metastatic disease are urgently needed.Tumor "self-homing" describes the recruitment of circulating tumor cells (CTCs) back to a previously excised primary tumor location, contributing to tumor recurrence, as well as their migration to established metastatic lesions.Recently, self-homing CTCs have been exploited as delivery vehicles for anti-cancer therapeutics in preclinical primary tumor models.However, the ability of CTCs to self-home and treat metastatic disease is largely unknown.Methods: Here, we used bioluminescence imaging (BLI) to explore whether systemically administered CTCs home to metastatic lesions and if CTCs armed with both a reporter gene and a cytotoxic prodrug gene therapy can be used to visualize and treat metastatic disease.Results: BLI performed over time revealed a remarkable ability of CTCs to home to and treat tumors throughout the body.Excitingly, metastatic tumor burden in mice that received therapeutic CTCs was lower compared to mice receiving control CTCs. Conclusion:This study demonstrates the noteworthy ability of experimental CTCs to home to disseminated breast cancer lesions.Moreover, by incorporating a prodrug gene therapy system into our self-homing CTCs, we show exciting progress towards effective and targeted delivery of gene-based therapeutics to treat both primary and metastatic lesions.
Non-Hodgkin Lymphoma With an Atypical Presentation
Authors: Guohua Shen, Anren Kuang
Journal: Clinical Nuclear Medicine (2020)

Abstract An 81-year-old woman was admitted with chest tightness and shortness of breath. Chest CT revealed massive pleural effusion on the right side as well as a right paravertebral soft tissue mass at the T8 to T10 level, showing intense enhancement. Her symptoms were successfully relieved by thoracentesis catheter drainage. On PET/CT, the paravertebral lesion demonstrated increased FDG uptake with an SUV max of 7.5, indicating a suspected diagnosis of malignancy. Eventually, a CT-guided needle biopsy was performed, which confirmed the diagnosis of non-Hodgkin lymphoma.