tbuckley/cabot-search huggingface dataset:
A rational approach to the prevention ofthromboembolic complications in the surgical treatment of complicated forms ofcholelithiasis in patients with liver cirrhosis
Authors: S.D. Khimich, F.T. Muraviov
Journal: GASTROENTEROLOGY (2021)

Background. It is known from scientific sources that a significant proportion of complications of liver cirrhosis is associated with negative impact of this pathology on the coagulation system. According to many scientists, liver cirrhosis in most cases poses a risk of developing both thrombotic and hemorrhagic complications. Objective: to identify a rational approach to the prevention of thromboembolic complications in the surgical treatment of complicated forms of cholelithiasis in patients with cirrhosis. Materials and methods. We retrospectively analyzed the hospital records of 62 patients who were treated for complicated forms of cholelithiasis with verified liver cirrhosis for the period from 2005 to 2018. The distribution of patients by nosology was as follows: acute calculous cholecystitis— 48 patients, Mirizzi syndrome— 7, choledocholithiasis— 7. Results. Based on a comparative analysis of two groups, the risk of intraoperative bleeding in patients with preoperative prophylaxis was higher (3cases— 8.1 %), with a blood loss of more than 400 ml. Hematomas of postoperative wounds were observed in 5 cases in group 1 and in one case in group 2. In the group of preoperative prophylaxis, portal vein thrombosis (n = 1), thrombosis of small branches of the pulmonary artery (n = 1), and deep vein thrombosis of the leg (n = 1) developed. No such complications were observed in the group with postoperative prophylaxis. Conclusions. The decision on the prevention of thromboembolic complications in this category of patients should be balanced and include an assessment of the risks of developing both hemorrhagic disorders and complications associated with thrombosis.
Abstract LB224: The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients.
Authors: Amichay Meirovitz, Daniela Nahmias, Esther Hermano, Ofra Maimon, Tamar Peretz, Michael Elkin
Journal: Cancer Research (2021)

Abstract Obesity serves as a risk factor for estrogen-dependent postmenopausal breast cancer (BC). While the exact association occurring between these two disease states remains unknown, obesity-associated inflammation is thought to be the most likely contributing factor. In addition, obesity has been correlated to changes in gut microbiota composition and a subsequent chronic increase in bacterial endotoxin (lipopolysaccharide [LPS] - canonic ligand of toll-like receptor 4 [TLR4]) blood levels. It was recently shown that BC cells intrinsically express TLR4 and such expression has been associated with decreased patient survival as well as increased tumor growth. We hypothesized that obesity-associated endotoxemia may contribute to BC progression by utilizing TLR-dependent mechanisms and exerting cancer-promoting effects directly (on carcinoma cells) and indirectly (triggering abnormal activation of macrophages). Utilizing a chronic metabolic endotoxemia and breast cancer murine model as well as in vitro experimental systems, we found that continuous exposure to low concentrations of LPS not only promotes BC progression in vivo but stimulates BC cell growth in culture through the activation of key breast cancer-promoting signaling pathways (Stat3, Akt, ERK1/2). Obesity has reached epidemic proportions globally, where elucidation of the molecular mechanisms underlying breast tumor-promoting action of obesity has become of vital importance. Improving the understanding of such mechanisms has the potential to reveal improved efficacious therapy regimens and prevention strategies in a rapidly growing population of obese, breast cancer patients. Citation Format: Amichay Meirovitz, Daniela Nahmias, Esther Hermano, Ofra Maimon, Tamar Peretz, Michael Elkin. The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB224.
Molecular pathogenesis of the myeloproliferative neoplasms
Authors: Graeme Greenfield, Mary Frances McMullin, Ken Mills
Journal: Journal of Hematology & Oncology (2021)

The Philadelphia negative myeloproliferative neoplasms (MPN) compromise a heterogeneous group of clonal myeloid stem cell disorders comprising polycythaemia vera, essential thrombocythaemia and primary myelofibrosis. Despite distinct clinical entities, these disorders are linked by morphological similarities and propensity to thrombotic complications and leukaemic transformation. Current therapeutic options are limited in disease-modifying activity with a focus on the prevention of thrombus formation. Constitutive activation of the JAK/STAT signalling pathway is a hallmark of pathogenesis across the disease spectrum with driving mutations in JAK2, CALR and MPL identified in the majority of patients. Co-occurring somatic mutations in genes associated with epigenetic regulation, transcriptional control and splicing of RNA are variably but recurrently identified across the MPN disease spectrum, whilst epigenetic contributors to disease are increasingly recognised. The prognostic implications of one MPN diagnosis may significantly limit life expectancy, whilst another may have limited impact depending on the disease phenotype, genotype and other external factors. The genetic and clinical similarities and differences in these disorders have provided a unique opportunity to understand the relative contributions to MPN, myeloid and cancer biology generally from specific genetic and epigenetic changes. This review provides a comprehensive overview of the molecular pathophysiology of MPN exploring the role of driver mutations, co-occurring mutations, dysregulation of intrinsic cell signalling, epigenetic regulation and genetic predisposing factors highlighting important areas for future consideration.
Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration
Authors: Angelika Więckowska-Gacek, Anna Mietelska-Porowska, Małgorzata Wydrych, Urszula Wojda
Journal: Ageing Research Reviews (2021)

An excess of saturated fatty acids and simple sugars in the diet is a known environmental risk factor of Alzheimer's disease (AD) but the holistic view of the interacting processes through which such diet may contribute to AD pathogenesis is missing. We addressed this need through extensive analysis of published studies investigating the effects of western diet (WD) on AD development in humans and laboratory animals. We reviewed WD-induced systemic alterations comprising metabolic changes, induction of obesity and adipose tissue inflammation, gut microbiota dysbiosis and acceleration of systemic low-grade inflammation. Next we provide an overview of the evidence demonstrating that WD-associated systemic alterations drive impairment of the blood-brain barrier (BBB) and development of neuroinflammation paralleled by accumulation of toxic amyloid. Later these changes are followed by dysfunction of synaptic transmission, neurodegeneration and finally memory and cognitive impairment. We conclude that WD can trigger AD by acceleration of inflammaging, and that BBB impairment induced by metabolic and systemic inflammation play the central role in this process. Moreover, the concurrence of neuroinflammation and Aβ dyshomeostasis, which by reciprocal interactions drive the vicious cycle of neurodegeneration, contradicts Aβ as the primary trigger of AD. Given that in 2019 the World Health Organization recommended focusing on modifiable risk factors in AD prevention, this overview of the sequential, complex pathomechanisms initiated by WD, which can lead from peripheral disturbances to neurodegeneration, can support future prevention strategies.
Survivorship, Version 1.2021
Authors: Amye Tevaarwerk, Crystal S. Denlinger, Tara Sanft, Shannon M. Ansbaugh, Saro Armenian, K. Scott Baker, Gregory Broderick, Andrew Day, Wendy Demark-Wahnefried, Kristin Dickinson, Debra L. Friedman, Patricia Ganz, Mindy Goldman, Norah Lynn Henry, Christine Hill-Kayser, Melissa Hudson, Nazanin Khakpour, Divya Koura, Allison L. McDonough, Michelle Melisko, Kathi Mooney, Halle C.F. Moore, Natalie Moryl, Javid J. Moslehi, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Chirayu Patel, Lindsay Peterson, William Pirl, M. Alma Rodriguez, Kathryn J. Ruddy, Lidia Schapira, Lillie Shockney, Sophia Smith, Karen L. Syrjala, Phyllis Zee, Nicole R. McMillian, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2021)

The NCCN Guidelines for Survivorship are intended to help healthcare professionals working with cancer survivors to ensure that each survivor's complex and varied needs are addressed. The Guidelines provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment; recommendations to help promote healthful lifestyle behaviors, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes the recommendations regarding employment and return to work for cancer survivors that were added in the 2021 version of the NCCN Guidelines.
Cryo-self-assembled silk fibroin sponge as a biodegradable platform for enzyme-responsive delivery of exosomes
Authors: Muyang Sun, Qi Li, Huilei Yu, Jin Cheng, Nier Wu, Weili Shi, Fengyuan Zhao, Zhenxing Shao, Qingyang Meng, Haifeng Chen, Xiaoqing Hu, Yingfang Ao
Journal: Bioactive Materials (2021)

Although advances in protein assembly preparation have provided a new platform for drug delivery during tissue engineering, achieving long-term controlled exosome delivery remains a significant challenge. Diffusion-dominated exosome release using protein hydrogels results in burst release of exosomes. Here, a fibroin-based cryo-sponge was developed to provide controlled exosome release. Fibroin chains can self-assemble into silk I structures under ice-cold conditions when annealed above the glass transition temperature. Exosome release is enzyme-responsive, with rates primarily determined by enzymatic degradation of the scaffolds. In vivo experiments have demonstrated that exosomes remain in undigested sponge material for two months, superior to their retention in fibrin glue, a commonly used biomaterial in clinical practice. Fibroin cryo-sponges were implanted subcutaneously in nude mice. The exosome-containing sponge group exhibited better neovascularization and tissue ingrowth effects, demonstrating the efficacy of this exosome-encapsulating strategy by realizing sustained release and maintaining exosome bioactivity. These silk fibroin cryo-sponges containing exosomes provide a new platform for future studies of exosome therapy.
SOX11, CD70, and Treg cells configure the tumor immune microenvironment of aggressive mantle cell lymphoma
Authors: Patricia Balsas, Luis Veloza, Guillem Clot, Marta Sureda-Gómez, Marta-Leonor Rodríguez, Christos Masaoutis, Gerard Frigola, Alba Navarro, Silvia Beà, Ferran Nadeu, Eva Giné, Armando López-Guillermo, Antonio Martínez, Inmaculada Ribera-Cortada, Pablo Engel, Leticia Quintanilla-Martínez, Wolfram Klapper, Elias Campo, Virginia Amador
Journal: Blood (2021)
Lived Experiences of Family Members of Patients With Severe COVID-19 Who Died in Intensive Care Units in France
Authors: Nancy Kentish-Barnes, Zoé Cohen-Solal, Lucas Morin, Virginie Souppart, Frédéric Pochard, Elie Azoulay
Journal: JAMA Network Open (2021)

During the initial surge of the COVID-19 pandemic, family members were often separated from their loved ones admitted to intensive care units (ICUs), with a potential for negative experiences and psychological burden.To better understand the experiences of bereaved family members of patients who died in an ICU during the COVID-19 pandemic, from the time of hospital admission until after the patient's death.This qualitative study used semistructured, in-depth interviews to collect experiences from bereaved family members of patients who died from severe COVID-19 in 12 ICUs during the first wave of the pandemic in France. Purposeful sampling was used to ensure the diversity of study participants with respect to sex, age, relationship with the patient, and geographic location. All data were collected between June and September 2020, and data analysis was performed from August to November 2020.Interviews were conducted 3 to 4 months after the patient's death and were audio-recorded and analyzed using thematic analysis.Among 19 family members interviewed (median [range] age, 46 [23-75] years; 14 [74%] women), 3 major themes emerged from qualitative analysis. The first was the difficulty in building a relationship with the ICU clinicians and dealing with the experience of solitude: family members experienced difficulties in establishing rapport and bonding with the ICU team as well as understanding the medical information. Distance communication was not sufficient, and participants felt it increased the feeling of solitude. The second involved the patient in the ICU and the risks of separation: because of restricted access to the ICU, family members experienced discontinuity and interruptions in the relationship with their loved one, which were associated with feelings of powerlessness, abandonment, and unreality. The third was regarding disruptions in end-of-life rituals: family members described "stolen moments" after the patient's death, generating strong feelings of disbelief that may lead to complicated grief.This qualitative study found that during the initial wave of the COVID-19 pandemic in France, bereaved family members described a disturbed experience, both during the ICU stay and after the patient's death. Specific family-centered crisis guidelines are needed to improve experiences for patients, families, and clinicians experiences.
Abstract 224: LAMP-2 Deficiency Promotes Mitochondrial Damage in Danon Disease
Authors: Sherin Hashem, Emily Gault, Anne Murphy, Neil Chi, Eric Adler
Journal: Circulation Research (2016)

Danon disease is a familial cardiomyopathy associated with impaired autophagic flux due to mutations in the gene encoding lysosomal associated membrane protein type 2 (LAMP-2). The majority of patients die from progressive heart failure in their twenties, yet to date the mechanisms by which LAMP-2 deficiency leads to cardiomyocyte dysfunction and death are not fully understood. To study the underlying molecular pathogenesis, we created induced pluripotent stem cell-derived cardiomyocytes (hiPSC- CMs) from patients with different LAMP-2 mutations, and reported an increase in apoptosis and mitochondrial oxidative stress. In Danon hiPSC-CMs, undigested mitochondria within double-membrane autophagosomes were frequently observed suggesting impaired mitophagy. Danon hiPSC-CMs displayed increased translocation of PARKIN and p62 on mitochondria, suggesting increased mitochondrial damage. When mitochondrial bioenergetic profile was assessed, Danon hiPSC-CMs showed a severe impairment in mitochondrial respiratory capacity even when offered various oxidizable substrates, suggesting global mitochondrial damage. In addition, Danon hiPSC-CMs demonstrated excessive mitochondrial fragmentation and low mitochondrial membrane potential. Lamp-2 knockout (KO) mice recapitulated key pathological features observed in Danon patients and their hiPSC-CMs. Lamp-2 KO mouse hearts exhibited abnormal mitochondria, increased mitochondrial damage, and impaired mitophagy. Interestingly, altered mitochondrial respiration was observed in Lamp-2 KO mouse hearts before the onset of significant impairment in contractile function. In summary, we have modeled Danon disease using hiPSC-CMs from patients with LAMP-2 mutations as well as Lamp-2 KO mice, allowing us to gain mechanistic insight into the pathogenesis of this disease. We demonstrate that LAMP-2 deficiency leads to impairment in mitophagic flux, accumulation of damaged mitochondria, and deterioration of mitochondrial function. Understanding the mechanisms underlying cardiomyocyte dysfunction will have important implications for the treatment of Danon disease as well as a various cardiovascular disorders associated with impaired autophagy.
STK39 promotes breast cancer invasion and metastasis by increasing SNAI1 activity upon phosphorylation
Authors: Zhaoping Qiu, Bo Dong, Weijie Guo, Rychahou Piotr, Greg Longmore, Xiuwei Yang, Zhiyong Yu, Jiong Deng, B Mark Evers, Yadi Wu
Journal: Theranostics (2021)

SNAI1 is widely regarded as a master driver of epithelial-mesenchymal transition (EMT) and associated with breast cancer progression and metastasis. This pro-malignant role is strongly linked to posttranslational modification, especially phosphorylation, which controls its protein levels and subcellular localization. While multiple kinases are implicated in regulation of SNAI1 stability, the precise mechanism by which SNAI1 is stabilized in tumors remains to be fully elucidated. Methods: A series of in vitro and in vivo experiments were conducted to reveal the regulation of SNAI1 by Serine/Threonine Kinase 39 (STK39) and the role of STK39 in breast cancer metastasis. Results: We identified STK39, a member of Stem 20-like serine/threonine kinase family, as a novel posttranslational regulator that enhances the stability of SNAI1. Inhibition of STK39 via knockdown or use of a specific inhibitor resulted in SNAI1 destabilization. Mechanistically, STK39 interacted with and phosphorylated SNAI1 at T203, which is critical for its nuclear retention. Functionally, STK39 inhibition markedly impaired the EMT phenotype and decreased tumor cell migration, invasion, and metastasis both in vitro and in vivo. These effects were rescued by ectopic SNAI1 expression. In addition, depletion of STK39 dramatically enhanced sensitivity to chemotherapeutic agents. Conclusions: Our study demonstrated that STK39 is a key mediator of SNAI1 stability and is associated with the pro-metastatic cellular process, highlighting the STK39-SNAI1 signaling axis as promising therapeutic targets for treatments of metastatic breast cancer.
Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial
Authors: Frederik Persson, Peter Rossing, Priya Vart, Glenn M. Chertow, Fan Fan Hou, Niels Jongs, John J.V. McMurray, Ricardo Correa-Rotter, Harpreet S. Bajaj, Bergur V. Stefansson, Robert D. Toto, Anna Maria Langkilde, David C. Wheeler, Hiddo J.L. Heerspink
Journal: Diabetes Care (2021)

OBJECTIVE The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status. RESEARCH DESIGN AND METHODS We enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200–5,000 mg/g. The primary composite end point was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. RESULTS Of 4,304 participants, 738 had normoglycemia, 660 had prediabetes, and 2,906 had type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (P for interaction = 0.19) in normoglycemia (hazard ratio [HR] 0.62 [95% CI 0.39, 1.01]), prediabetes (HR 0.37 [0.21, 0.66]), and type 2 diabetes (HR 0.64 [0.52, 0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes. CONCLUSIONS Dapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status.
Magnetoelectric Nanoparticles Incorporated Biomimetic Matrix for Wireless Electrical Stimulation and Nerve Regeneration
Authors: Yusheng Zhang, Suping Chen, Zhanwen Xiao, Xiaoyin Liu, Chengheng Wu, Kai Wu, Amin Liu, Dan Wei, Jing Sun, Liangxue Zhou, Hongsong Fan
Journal: Advanced Healthcare Materials (2021)

Abstract Electrical stimulation is regarded pivotal to promote repair of nerve injuries, however, failed to get extensive application in vivo due to the challenges in noninvasive electrical loading accompanying with construction of biomimetic cell niche. Herein, a new concept of magneto responsive electric 3D matrix for remote and wireless electrical stimulation is demonstrated. By the preparation of magnetoelectric core/shell structured Fe 3 O 4 @BaTiO 3 NPs‐loaded hyaluronan/collagen hydrogels, which recapitulate considerable magneto‐electricity and vital features of native neural extracellular matrix, the enhancement of neurogenesis both in cellular level and spinal cord injury in vivo with external pulsed magnetic field applied is proved. The findings pave the way for a novel class of remote controlling and delivering electricity through extracellular niches‐mimicked hydrogel network, arising prospects not only in neurogenesis but also in human–computer interaction with higher resolution.
Matt Morgan: Whose leg is it anyway? Ownership and medicine
Authors: Matt Morgan
Journal: BMJ (2021)

Brain metastases (BM) are the most common intracranial neoplasm in adults. Initially considered as an essentially terminal stage of advanced cancer, BM are increasingly being recognized as an emerging area of clinical interest. Their epidemiological characteristics have changed significantly, including an increased incidence in tumors frequently associated with BM, such as lung and breast cancer or melanoma, but also a more frequent occurrence with other primary tumor entities such as renal, colorectal and ovarian cancer. BM are more commonly diagnosed in multiple intracerebral sites, but in the context of controlled extracranial disease. Accordingly, progress in the development of systemic treatments, together with the rationalized use of surgical resection, radiosurgery and whole-brain radiotherapy, have led to an increase in the number of long-term survivors and in median survival. The recent emergence of targeted therapies and growing knowledge regarding the specific biology of BM should allow further improvements in prognosis of this devastating disease.
Usefulness of Cardiovascular Magnetic Resonance to Predict Life Threatening Ventricular Arrhythmias in Patients with Dilated Cardiomyopathy
Authors: Chimura Misato, Okajima Katsunori, Shimane Akira, Kiuchi Kunihiko, Kanda Gaku, Yokoi Kiminobu, Teranishi Jin, Aoki Kosuke, Hayashi Takatoshi, Yasaka Yoshinori, Taniguchi Yasuyo, Yamada Shinichiro, Takaya Tomofumi, Miyoshi Naoki, Ohishi Shogo, Toba Takayoshi, Takahashi Hachidai, Miyata Taishi, Saita Ten, Kobayashi Seiichi, Yokoyama Mitsuhiro
Journal: Circulation (2013)
Dietary omega 3 fatty acids for migraine
Authors: Rebecca Burch
Journal: BMJ (2021)

Dietary omega 3 fatty acids for migraineAt last, grounds for optimism among those seeking a dietary option Rebecca Burch medical doctorMigraine is one of the most common neurological diseases and affects one billion people globally. 1 The past several years have seen the introduction of several new acute and preventive treatments for migraine, but patient and clinician interest in non-pharmacological treatments, including dietary changes, remains strong.
Abstract 10901: 4D Flow versus 2D Cardiac MRI for the Evaluation of Pulmonary Regurgitation and Ventricular Volume in Repaired Tetralogy of Fallot
Authors: Kimberley Jacobs, Frandics Chan, Joseph Y Cheng, Shreyas Vasanawala, Shiraz Maskatia
Journal: Circulation (2018)

Background: Limitations of traditional 2D cardiac MRI (2D CMR) are breath holding and long exam times. 3D time-resolved flow (4DF) MRI is a 5-10 minute, free-breathing, single-sequence exam that si...