tbuckley/cabot-search huggingface dataset:
Locoregional nodal extension does not impair prognosis of primary cutaneous anaplastic lymphomas
Authors: M. D’Incan, S. Ingen‐Housz‐Oro, M. Beylot‐Barry, P. Joly, F. Grange, G. Quereux, I. Templier, C. Ram‐Wolff, H. Adamski, C. Lambert, C. Descours
Journal: British Journal of Dermatology (2020)
Advanced protein adsorption properties of a novel silicate-based bioceramic: A proteomic analysis
Authors: Fanyan Deng, Wanyin Zhai, Yue Yin, Chao Peng, Congqin Ning
Journal: Bioactive Materials (2020)

Silicate bioceramics have been shown to possess excellent cytocompatibility and osteogenic activity, but the exact mechanism is still unclear. Protein adsorption is the first event taking place at the biomaterial-tissue interface, which is vital to the subsequent cellular behavior and further influence the biomaterial-tissue interaction. In this work, the protein adsorption behavior of a novel CPS bioceramic was evaluated using the proteomics technology. The results showed that CPS adsorbed more amount and types of serum proteins than HA. FN1 and IGF1 proteins selected from proteomics results were validated by Western-blot experiment. Pathway analysis also revealed mechanistic insights how these absorbed proteins by CPS help mediate cell adhesion and promotes osteogenic activity. Firstly, the dramatically enhanced adsorption of FN1 could greatly promote cell adhesion and growth. Secondly, IGF1 was uniquely adsorbed on CPS bioceramic and IGF1 could activate Rap1 signaling pathway to promote cell adhesion. Thirdly, the increased adsorption of FN1, IGF1 and COL1A2 proteins on CPS explains its better ability on bone regeneration than HA. Fourthly, the increased adsorption of IGF1, CHAD, COL2A1 and THBS4 proteins on CPS explains its ability on cartilage formation. Lastly, the increased adsorption of immunological related proteins on CPS may also play a positive role in bone regeneration. In addition, CPS had a much better cell adhesion ability than HA, proving that more adsorbed proteins really had a positive effect on cell behavior. The more adsorbed proteins on CPS than HA might indicated a better bone regeneration rate at early stage of implantation.
Novel platform leveraging electronic medical record (EMR) to triage patients admitted with high-grade immune-related adverse events (irAEs) to the immune-toxicity (ITOX) service
Authors: Osama Abu-Shawer, Prabhsimranjot Singh, Eric Yenulevich, Amanda Brito, Jian Ni, Raja-Elie E Abdulnour, Shilpa Grover, Michael Manos, Peter Bowling, Nicole R LeBoeuf, Patrick Ott, F Stephen Hodi, Joseph Jacobson, Osama Rahma
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The incidence of high-grade immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) is increasing due to the rapid expansion of indications for their use. There is an urgent need for a feasible approach of identifying patients with high-grade irAEs to ensure early detection and proper management of this unique set of toxicities. Methods We established one of the first inpatient services that are specifically devoted to mitigating irAEs. The service uses a multidisciplinary approach with consulting service from experts in managing irAEs. We are leveraging the electronic medical record (EMR) to triage patients who are admitted to the hospital and have received or are currently receiving ICIs. A list of patients with ICI exposure is generated daily by EMR and then curated manually to identify patients with potential irAEs. Results A total of 129 patients with high-grade irAEs were admitted between June 2018 and June 2019. The most common irAEs were colitis (32%), pneumonitis (30%), and hepatitis (14%). Eighty five per cent of the patients had grade 3 irAEs and 15% had grade 4–5. About half of the patients had received ICI monotherapy; 30% had received combination of ICIs and non-ICIs; and 19% had received a combination of ICIs. Only 9% of patients had steroid-refractory irAEs requiring other immunosuppressive agents. The average length of stay for irAE-related admission was 11 days with a readmission rate due to recurrent irAEs of 26% within a year. Conclusion We demonstrated the feasibility of using the EMR to accurately triage patients with suspected irAEs to a dedicated immune-toxicity service. Our model is adaptable in major academic centers and could have a major impact on quality of care and future clinical research addressing irAEs.
PRDM12: New Opportunity in Pain Research
Authors: Sophie Imhof, Tomislav Kokotović, Vanja Nagy
Journal: Trends in Molecular Medicine (2020)

PRDM12 is a newly identified causative gene for a type of congenital insensitivity to pain disorder, which is characterized by the inability to perceive pain. Here, we discuss the (patho)physiology of PRDM12 function and the opportunities and challenges those data provide for novel therapeutic approaches in various pain disorders.
The Promise of Clinical Decision Support Systems Targetting Low-Resource Settings
Authors: Dani Kiyasseh, Tingting Zhu, David Clifton
Journal: IEEE Reviews in Biomedical Engineering (2020)

Low-resource clinical settings are plagued by low physician-to-patient ratios and a shortage of high-quality medical expertise and infrastructure. Together, these phenomena lead to over-burdened healthcare systems that under-serve the needs of the community. Alleviating this burden can be undertaken by the introduction of clinical decision support systems (CDSSs); systems that support stakeholders (ranging from physicians to patients) within the clinical setting in their day-to-day activities. Such systems, which have proven to be effective in the developed world, remain to be under-explored in low-resource settings. This review attempts to summarize the research focused on clinical decision support systems that either target stakeholders within low-resource clinical settings or diseases commonly found in such environments. When categorizing our findings according to disease applications, we find that CDSSs are predominantly focused on dealing with bacterial infections and maternal care, do not leverage deep learning, and have not been evaluated prospectively. Together, these highlight the need for increased research in this domain in order to impact a diverse set of medical conditions and ultimately improve patient outcomes.
Behavioral Counseling Interventions to Prevent Sexually Transmitted Infections
Authors: Alex H. Krist, Karina W. Davidson, Carol M. Mangione, Michael J. Barry, Michael Cabana, Aaron B. Caughey, Katrina Donahue, Chyke A. Doubeni, John W. Epling, Martha Kubik, Gbenga Ogedegbe, Lori Pbert, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2020)

<h3>Importance</h3> Approximately 20 million new cases of bacterial or viral sexually transmitted infections (STIs) occur each year in the US, and about one-half of these cases occur in persons aged 15 to 24 years. Rates of chlamydial, gonococcal, and syphilis infection continue to increase in all regions. Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others. Serious consequences of STIs include pelvic inflammatory disease, infertility, cancer, and AIDS. <h3>Objective</h3> To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the benefits and harms of behavioral counseling interventions for preventing STI acquisition. <h3>Population</h3> This recommendation statement applies to all sexually active adolescents and to adults at increased risk for STIs. <h3>Evidence Assessment</h3> The USPSTF concludes with moderate certainty that behavioral counseling interventions reduce the likelihood of acquiring STIs in sexually active adolescents and in adults at increased risk, including for example, those who have a current STI, do not use condoms, or have multiple partners, resulting in a moderate net benefit. <h3>Recommendation</h3> The USPSTF recommends behavioral counseling for all sexually active adolescents and for adults at increased risk for STIs. (B recommendation)
E-patients hold key to the future of healthcare
Authors: Sara Riggare
Journal: British Journal of Sports Medicine (2020)

Today, patients are using the internet and other technologies as well as fellow patients to diagnose their own problems, find the best treatment, continually optimise their treatments, and even fund and conduct research.1 They are doing this not thanks to, but despite, healthcare.

The impression is that many clinicians would rather patients didn’t use Google for healthcare, and patients are keen not to annoy the people whose help we need. Of course, patients with chronic or long term conditions can become experts in their illness, but patients who show clinical knowledge sometimes experience disbelief or even active opposition from professionals. Work by The BMJ ’s former patient editor Rosamund Snow showed how people with type 1 diabetes and high health literacy were hindered by healthcare professionals who were not experts in the specialty.2 

What should the new healthcare look like? We don’t know for sure, but 17 years ago, Tom Ferguson, a health informatics professor, argued that physicians and other healthcare professionals should embrace the efforts of active patients.3 He said that granting patients’ wishes for more online communication with their doctors could reduce consultation times. He coined the term ‘e-patients’ to mean patients (or their friends or relatives) who seek health related information online,4 which results in ‘better health information and services, and different (but not always better) relationships with their doctors.’5 

### How I became an e-patient

I was 32 when I had Parkinson’s disease diagnosed in June 2003, but I had known that something was wrong for almost 18 years. I experienced the first symptoms in my teens, and a few years later was diagnosed as having generalised dystonia.

I researched this diagnosis for hours in the library in the suburb of Stockholm where I grew …
Three-Year Outcomes of Bariatric Surgery in Patients With Obesity and Hypertension
Authors: Carlos A. Schiavon, Deepak L. Bhatt, Dimas Ikeoka, Eliana V. Santucci, Renato Nakagawa Santos, Lucas P. Damiani, Juliana D. Oliveira, Rachel Helena V. Machado, Helio Halpern, Frederico L.J. Monteiro, Patricia M. Noujaim, Ricardo V. Cohen, Marcio G. de Souza, Celso Amodeo, Luiz A. Bortolotto, Otavio Berwanger, Alexandre B. Cavalcanti, Luciano F. Drager
Journal: Annals of Internal Medicine (2020)

Background: Midterm effects of bariatric surgery on patients with obesity and hypertension remain uncertain. Objective: To determine the 3-year effects of Roux-en-Y gastric bypass (RYGB) on blood pressure (BP) compared with medical therapy (MT) alone. Design: Randomized clinical trial. (ClinicalTrials.gov: NCT01784848) Setting: Investigator-initiated study at Heart Hospital (HCor), São Paulo, Brazil. Participants: Patients with hypertension receiving at least 2 medications at maximum doses or more than 2 medications at moderate doses and with a body mass index (BMI) between 30.0 and 39.9 kg/m2 were randomly assigned (1:1 ratio). Intervention: RYGB plus MT or MT alone. Measurements: The primary outcome was at least a 30% reduction in total number of antihypertensive medications while maintaining BP less than 140/90 mm Hg. Key secondary outcomes were number of antihypertensive medications, hypertension remission, and BP control according to current guidelines (<130/80 mm Hg). Results: Among 100 patients (76% female; mean BMI, 36.9 kg/m2 [SD, 2.7]), 88% from the RYGB group and 80% from the MT group completed follow-up. At 3 years, the primary outcome occurred in 73% of patients from the RYGB group compared with 11% of patients from the MT group (relative risk, 6.52 [95% CI, 2.50 to 17.03]; P < 0.001). Of the randomly assigned participants, 35% and 31% from the RYGB group and 2% and 0% from the MT group achieved BP less than 140/90 mm Hg and less than 130/80 mm Hg without medications, respectively. Median (interquartile range) number of medications in the RYGB and MT groups at 3 years was 1 (0 to 2) and 3 (2.8 to 4), respectively (P < 0.001). Total weight loss was 27.8% and −0.1% in the RYGB and MT groups, respectively. In the RYGB group, 13 patients developed hypovitaminosis B12 and 2 patients required reoperation. Limitation: Single-center, nonblinded trial. Conclusion: RYGB is an effective strategy for midterm BP control and hypertension remission, with fewer medications required in patients with hypertension and obesity. Primary Funding Source: Ethicon, represented in Brazil by Johnson & Johnson do Brasil.
Inguinal Canal Deposit—An Uncommon Site of Metastases in Carcinoma Prostate Detected on 68Ga–Prostate-Specific Membrane Antigen PET/CT
Authors: Saurabh Arora, Sanjay Kumar, Chandan Jyoti Das, Deepali Jain, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2020)

Metastatic deposit in the inguinal canal is an uncommon finding. Few tumors such as pancreatic cancer, rectal cancer, and ovarian cancer have been described previously with metastatic inguinal canal deposit. We present here a case of prostate cancer with an uncommon inguinal canal deposit that was detected on Ga-prostate-specific membrane antigen PET/CT.
Reverse Trigger Phenotypes in Acute Respiratory Distress Syndrome
Authors: Elias Baedorf Kassis, Henry K. Su, Alexander R. Graham, Victor Novack, Stephen H. Loring, Daniel S. Talmor
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Reverse triggering is an underexplored form of dyssynchrony with important clinical implications in patients with acute respiratory distress syndrome.Objectives: This retrospective study identified reverse trigger phenotypes and characterized their impacts on Vt and transpulmonary pressure.Methods: Fifty-five patients with acute respiratory distress syndrome on pressure-regulated ventilator modes were included. Four phenotypes of reverse triggering with and without breath stacking and their impact on lung inflation and deflation were investigated.Measurements and Main Results: Inflation volumes, respiratory muscle pressure generation, and transpulmonary pressures were determined and phenotypes differentiated using Campbell diagrams of respiratory activity. Reverse triggering was detected in 25 patients, 15 with associated breath stacking, and 13 with stable reverse triggering consistent with respiratory entrainment. Phenotypes were associated with variable levels of inspiratory effort (mean 4–10 cm H2O per phenotype). Early reverse triggering with early expiratory relaxation increased Vts (88 [64–113] ml) and inspiratory transpulmonary pressures (3 [2–3] cm H2O) compared with passive breaths. Early reverse triggering with delayed expiratory relaxation increased Vts (128 [86–170] ml) and increased inspiratory and mean-expiratory transpulmonary pressure (7 [5–9] cm H2O and 5 [4–6] cm H2O). Mid-cycle reverse triggering (initiation during inflation and maximal effort during deflation) increased Vt (51 [38–64] ml), increased inspiratory and mean-expiratory transpulmonary pressure (3 [2–4] cm H2O and 3 [2–3] cm H2O), and caused incomplete exhalation. Late reverse triggering (occurring exclusively during exhalation) increased mean expiratory transpulmonary pressure (2 [1–2] cm H2O) and caused incomplete exhalation. Breath stacking resulted in large delivered volumes (176 [155–197] ml).Conclusions: Reverse triggering causes variable physiological effects, depending on the phenotype. Differentiation of phenotype effects may be important to understand the clinical impacts of these events.
Impact of Early Revascularization on Major Adverse Cardiovascular Events in Relation to Automatically Quantified Ischemia
Authors: Peyman N Azadani, Robert J H Miller, Tali Sharir, Marcio A Diniz, Lien-Hsin Hu, Yuka Otaki, Heidi Gransar, Joanna X Liang, Evann Eisenberg, Andrew J Einstein, Mathews B Fish, Terrence D Ruddy, Philipp A Kaufmann, Albert J Sinusas, Edward J Miller, Timothy M Bateman, Sharmila Dorbala, Marcelo Di Carli, Balaji K Tamarappoo, Damini Dey, Daniel S Berman, Piotr J Slomka
Journal: JACC. Cardiovascular imaging (2020)
Prolonged Molecular and Clinical Remissions in Follicular Lymphoma Patients Treated with HDT/ASCT and Combination Immunotherapy with Rituximab and Interferon α
Authors: Liam Smyth, Rena Buckstein, Pennell Nancy, Rashmi Weerasinghe, Matthew Cheung, Eugenia Piliotis, Kevin Imrie, David Spaner, Marciano D. Reis, Lisa Chodirker, Zeina Ghorab, Milliken, Violet ruth,nancy, Angela Boudreau, Neil Berinstein
Journal: Blood (2017)
Structural, functional, and mechanistic insights uncover the fundamental role of orphan connexin-62 in platelets
Authors: Khaled A. Sahli, Gagan D. Flora, Parvathy Sasikumar, Ali H. Maghrabi, Lisa-Marie Holbrook, Sarah K. AlOuda, Amro Elgheznawy, Tanya Sage, Alexander R. Stainer, Recep Adiyaman, Mohammad AboHassan, Marilena Crescente, Neline Kriek, Sakthivel Vaiyapuri, Alexander P. Bye, Amanda J. Unsworth, Chris I. Jones, Liam J. McGuffin, Jonathan M. Gibbins
Journal: Blood (2020)
Modulating immunosuppression in liver transplant patients with COVID-19
Authors: Manuel Rodriguez-Peralvarez, Magdalena Salcedo, Jordi Colmenero, Jose Antonio Pons
Journal: Gut (2020)

We read with great interest the COVID-LT study by C Becchetti et al ,1 which included 57 liver transplant (LT) patients from 12 European institutions who were diagnosed with coronavirus disease 2019 (COVID-19). Simultaneously, the Spanish Society of Liver Transplantation (SETH) has conducted a nationwide prospective study including 22 transplant institutions and 111 LT patients with COVID-19.2 Since there were only nine overlapped cases, both cohorts add up to 159 LT patients and taken together their close analysis (table 1) may derive in practical conclusions.

View this table:

Table 1 
Clinical characteristics and outcomes of LT patients included in the European COVID-LT cohort and in the nationwide study from the Spanish Society of Liver Transplantation (SETH)



The crude incidence of COVID-19 was increased in the SETH study as compared with the COVID-LT study (0.84% vs 0.48%), even with a shorter recruitment period. This could be explained because the SETH study was performed during the outbreak period in Spain, one of the toughest in Europe.3 The SETH study allowed …
A fully defined 3D matrix for ex vivo expansion of human colonic organoids from biopsy tissue
Authors: Fredrik Bergenheim, Giulia Fregni, Cara Field Buchanan, Lene Buhl Riis, Mathieu Heulot, Jeremy Touati, Jakob Benedict Seidelin, Simone Carlo Rizzi, Ole Haagen Nielsen
Journal: Biomaterials (2020)

Intestinal organoids have widespread research and biomedical applications, such as disease modeling, drug testing and regenerative medicine. However, the transition towards clinical use has in part been hampered by the dependency on animal tumor-derived basement membrane extracts (BMEs), which are poorly defined and ill-suited for regulatory approval due to their origin and batch-to-batch variability. In order to overcome these limitations, and to enable clinical translation, we tested the use of a fully defined hydrogel matrix, QGel CN99, to establish and expand intestinal organoids directly from human colonic biopsies. We achieved efficient de novo establishment, expansion and organoid maintenance, while also demonstrating sustained genetic stability. Additionally, we were able to preserve stemness and differentiation capacity, with transcriptomic profiles resembling normal colonic epithelium. All data proved comparable to organoids cultured in the BME-benchmark Matrigel. The application of a fully defined hydrogel, completely bypassing the use of BMEs, will drastically improve the reproducibility and scalability of organoid studies, but also advance translational applications in personalized medicine and stem cell-based regenerative therapies.
IGF-I stimulates the migratory behavior of prostate cancer cells: possible mechanism of action
Authors: Patrizia Limonta, Roberta M. Moretti, Marina Montagnani Marelli
Journal: Cancer Research (2005)

5647  Prostate cancer (CaP), which is usually androgen-dependent in its early stages, very often progresses to a condition of insensitivity to testicular steroids. Androgen-independent CaP is characterized by a high proliferation rate and by a strong ability of cancer cells to invade surrounding tissues and to give rise to metastases. The molecular mechanisms underlying the metastatic behavior of CaP cells are still unclear. IGF-I plays a crucial role in the control of CaP growth. The experiments here to be described have been performed to clarify whether IGF-I might also be involved in the control of the metastatic behavior of androgen-independent (DU 145) CaP cells, expressing the IGF-I receptor. We have shown that IGF-I stimulates the motility of DU 145 cells towards fibronectin, as evaluated by means of a haptotactic assay in a Boyden’s chamber. The effect was found to be specific since it was completely abrogated by the simultaneous treatment of the cells with an antibody directed against the IGF-I receptor. The pro-migratory activity of IGF-I was significantly counteracted by a simultaneous treatment of the cells with the PI3K inhibitor LY294002, indicating that the phosphorylation of the Akt kinase plays a crucial role in the action of the growth factor. Upon IGF-I treatment, DU 145 cells underwent morphological changes assuming a flattened contour with filopodia formation, accompanied by a rearrangement of the actin cytoskeleton. We have finally demonstrated that the alphavbeta3 integrin dimer is deeply involved in the migratory behavior of DU 145 cells. The treatment of DU 145 cells with IGF-I resulted in a significant increase of alphavbeta3 integrin expression, as investigated by Western blot analysis and by immunocytochemistry. Moreover, the pro-migratory activity of IGF-I on DU 145 cells was completely abrogated in the presence of an antibody against alphavbeta3. These data indicate that: 1) IGF-I significantly increases the motility of androgen-independent prostate cancer cells, possibly through the PI3K/Akt pathway; 2) the growth factor exerts its pro-metastatic activity by increasing the expression of the integrin alphavbeta3.
Imaging of Clinically Unrecognized Myocardial Fibrosis in Patients With Suspected Coronary Artery Disease
Authors: Panagiotis Antiochos, Yin Ge, Kevin Steel, Scott Bingham, Shuaib Abdullah, J. Ronald Mikolich, Andrew E. Arai, W. Patricia Bandettini, Amit R. Patel, Afshin Farzaneh-Far, John F. Heitner, Chetan Shenoy, Steve W. Leung, Jorge A. Gonzalez, Dipan J. Shah, Subha V. Raman, Victor A. Ferrari, Jeanette Schulz-Menger, Matthias Stuber, Orlando P. Simonetti, Raymond Y. Kwong
Journal: Journal of the American College of Cardiology (2020)
PRC2 insufficiency causes p53-dependent dyserythropoiesis in myelodysplastic syndrome
Authors: Kazumasa Aoyama, Daisuke Shinoda, Emi Suzuki, Yaeko Nakajima-Takagi, Motohiko Oshima, Shuhei Koide, Ola Rizq, Sha Si, Shiro Tara, Goro Sashida, Atsushi Iwama
Journal: Leukemia (2020)