tbuckley/cabot-search huggingface dataset:
The Role of Perfusion Computed Tomography as a Predictor of Pancreatic Necrosis in Acute Pancreatitis
Authors: N. V. Klimova, V. V. Darvin, I. V. Bazhukhina, A. A. Gaus
Journal: Radiology - Practice (2021)

The presented article analyzes the data obtained as a result of the applied imaging methods of the study of 38 patients admitted to the surgical department of the Surgut Regional Clinical Hospital with suspicion of acute pancreatitis. The main criterion for inclusion in the study was the period from the onset of the initial symptoms of the disease, which did not exceed three days. In the hospital, all patients underwent perfusion computed tomography (PCT) in the first 3 days and subsequently, in accordance with national recommendations, multislice computed tomography (MSCT) with bolus intravenous contrast enhancement for 3–5 days. In 31,5 % of cases (12 out of 38 patients), a violation of the perfusion characteristics of the pancreatic parenchyma corresponding to ischemic tissue damage was diagnosed. MSCT with bolus intravenous contrast enhancement confirmed the presence of a formed zone of necrosis of the pancreatic tissue in 21 % of patients. In 10,5 % of cases, progression of ischemic damage to the pancreatic tissue was not revealed by MSCT, which was confirmed by further observation of this group of patients. Based on the study, conclusions were drawn about the ability of perfusion CT to serve as an effective predictor of pancreatic necrosis, which makes it possible to choose the optimal surgical tactics at the early stages of treatment of such patients.
Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study
Authors: Emmy Okello, Emma Ndagire, Babu Muhamed, Rachel Sarnacki, Meghna Murali, Jafesi Pulle, Jenifer Atala, Asha C Bowen, Marc P DiFazio, M G Nakitto, Nada S Harik, Rosemary Kansiime, Chris T Longenecker, Peter Lwabi, Collins Agaba, Scott A Norton, Isaac Otim Omara, Linda Mary Oyella, Tom Parks, Joselyn Rwebembera, Christopher F Spurney, Elizabeth Stein, Laura Tochen, David Watkins, Meghan Zimmerman, Jonathan R Carapetis, Craig A Sable, Andrea Beaton
Journal: The Lancet Global Health (2021)

BackgroundAcute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda.MethodsFor our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3–17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5–14 years and characterised clinical features of definite and possible acute rheumatic fever cases.FindingsData were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5–14 years as 25 cases (95% CI 13·7–30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1–21·0) per 100 000 person-years in Mbarara district (west).InterpretationTo the best of our knowledge, this is the first population-based study to estimate the incidence of acute rheumatic fever in sub-Saharan Africa. Given the known rheumatic heart disease burden, it is likely that only a proportion of children with acute rheumatic fever were diagnosed. These data dispel the long-held hypothesis that the condition does not exist in sub-Saharan Africa and compel investment in improving prevention, recognition, and diagnosis of acute rheumatic fever.FundingAmerican Heart Association Children's Strategically Focused Research Network Grant, THRiVE-2, General Electric, and Cincinnati Children's Heart Institute Research Core.
Pancreatic Cancer Progression in a Patient With Lynch Syndrome Receiving Immunotherapy: A Cautionary Tale
Authors: Yifan Wang, Adeline Cuggia, Alain Pacis, Jean-Christian Boileau, Victoria A. Marcus, Zu-Hua Gao, George Chong, William D. Foulkes, George Zogopoulos
Journal: Journal of the National Comprehensive Cancer Network (2021)

Pancreatic ductal adenocarcinomas (PDACs) with DNA mismatch repair deficiency (MMRd) respond preferentially to immune checkpoint inhibitors (ICIs). However, a subset of MMRd PDACs does not respond to these agents. This report describes a patient with PDAC who experienced rapid disease progression suggestive of hyperprogressive disease. The case involved a 63-year-old man carrying a pathogenic germline PMS2 mutation who developed metastatic PDAC. His tumor showed isolated loss of PMS2 expression by immunohistochemistry (IHC). He was treated with pembrolizumab, but his disease rapidly progressed. Whole-genome and transcriptome sequencing of a liver metastasis biopsy, acquired at disease progression, showed a retained wild-type PMS2 allele and hallmarks of microsatellite stability, including low tumor mutational burden and low MSIsensor score. PCR-based microsatellite instability (MSI) testing of the treatment-naïve tumor showed microsatellite stability. The ICI-treated tumor had a lower density of CD8+ T-cell infiltration than the treatment-naïve tumor, which is contrary to the expected evolution with ICI responsiveness. Through this case and a review of the literature, we highlight the low penetrance of PMS2 germline mutations in PDAC and discuss pitfalls in ascertaining MMRd and MSI based on IHC testing alone. An orthogonal confirmatory assay is warranted in the presence of uncommon immunophenotypes, such as isolated PMS2 loss, to optimize selection of patients with PDAC for immunotherapy.
SEM Switzerland: making sport safer and breaking down silos
Authors: Boris Gojanovic
Journal: British Journal of Sports Medicine (2021)

The past year has been a repetitive tale of challenges and adaptations, as each new wave of the pandemic spread across the world. One striking feature has been each country or region’s race for ‘safe ground’, including border closures and idiosyncratic rules and regulations. When the going gets tough, everyone seems to revert to strategies of the past, usually involving silos and fences. Sometimes, this happens in medicine too. As problems become more complex, specialised care and specialists become more isolated from one another, meaning they cannot see the forest for the trees.

SEM clinicians have a strong culture of transversal collaboration, necessary because of the complex multistakeholder environment and the extreme pressure we have to navigate. As challenging as it is, the pandemic has added a new layer by erasing most in-person …
26916 Effectiveness of guselkumab among patients with moderate-to-severe plaque psoriasis in the Corrona Psoriasis Registry
Authors: April W. Armstrong, Kristina Callis-Duffin, Timothy Fitzgerald, Amanda Teeple, Jonathan Uy, Mobolaji Olurinde, Katelyn Rowland, Robert R. McLean, Lin Guo, Ying Shan, Abby S. Van Voorhees
Journal: Journal of the American Academy of Dermatology (2021)
26433 Interventions for skin wellbeing clinics in for health care staff during the SARS-CoV2 outbreak: A perspective from London (UK)
Authors: Nav Paul, Monika Saha, Marie-Louise Daly, Luigi Citarella, Antonia D’Cruz, Athina Fonia, Rachel Healy, Ljubomir Novakovic, Alison Shanks, Kavitha Sundararaj
Journal: Journal of the American Academy of Dermatology (2021)

Introduction: An acute increase of dermatologic conditions occurred in National Healthcare System (NHS) health care workers (HCW) during the SARS-CoV2 outbreak. Novel "skin wellbeing" clinics were established to support colleagues. Methods: HCW self-referred to dermatologists during an 8-week period in spring 2020. Clinics were supported by clinical nurse specialists in tandem to a publication of a departmental advice leaflet. Attendees were provided with samples of emollients, dressings, prescriptions and consultations free of charge. Results: A total of 90 electronic medical records were analyzed retrospectively. Parameters included age, sex, ethnicity, diagnosis, previous history, interventions, and investigations. Of 80 new attendances, the commonest complaint was hand dermatitis (57; 71%) followed by (PPE) related skin conditions (33; 41.3%) and flares of pre-existing skin disease (15; 18.8%). A total of 197 separate prescription items were issued. Topical corticosteroid prescriptions were comprised of mild (9), moderate (23), potent (27) and very potent (14) preparations, 4 combined with calcipotriol monohydrate, fusidic acid 2%, miconazole nitrate 2% and clotrimazole 1.0%. Other topical preparations included ketoconazole 2% (1), tacrolimus 0.1% (3), ivermectin 1% (1), azelaic acid 15% (1), adapalene 0.1% (1), adapalene with benzoyl peroxide (1), and combined clindamycin 1% with benzoyl peroxide 5% (8). Oral prescription medications included lymecycline (1) and doxycycline (1). Remaining items included emollients, soap substitutes, cleansing solutions and barrier creams. Discussion: Our study demonstrates a significant burden of occupational dermatologic disease in HCWs as a direct consequence of the pandemic. We discuss measures implemented locally to aid staff recovery and share our experience.
Vaccines should not be the preserve of rich countries
Authors: Fiona Godlee
Journal: BMJ (2021)

Since their 18th century beginnings vaccines have been one of humanity’s most profound public health interventions, preventing illness and death on a massive scale, eradicating the global scourge of smallpox, and potentially soon doing the same for polio. But while some parts of the world bask in the success of their covid vaccination programmes others are struggling to gain even a foothold. Such gross inequities are causing much preventable suffering, needlessly prolonging the pandemic, and leaving us all at risk of vaccine resistant variants.

Fatima Hassan and colleagues are in no doubt of the causes of this “vaccine apartheid” (doi:10.1136/bmj.n2027).1 It is not a lack of manufacturing capacity: it is possible to make …
A functional BCI model by the IEEE P2731 working group: data storage and sharing
Authors: Luigi Bianchi, Alberto Antonietti, Garima Bajwa, Raffaele Ferrante, Mufti Mahmud, Pradeep Balachandran
Journal: Brain-Computer Interfaces (2021)

The IEEE P2731 working group is in the process of developing a functional model so that virtually any BCI system could be described according to it. In this paper, we want to stimulate the discussion for the definition and selection of the information that should be stored in a file for effectively allowing the sharing of BCI data and tools amongst researchers. Establishing these requirements and procedures will accelerate BCI development and lay the foundation for accessible and scalable BCI technology as well as provide the foundations for the definition of a standard file format.
Effect of <scp>JAK</scp> Inhibition on the Induction of Proinflammatory <scp>HLA</scp>–<scp>DR</scp>+<scp>CD90</scp>+ Rheumatoid Arthritis Synovial Fibroblasts by Interferon‐γ
Authors: Shuyang Zhao, Ricardo Grieshaber‐Bouyer, Deepak A. Rao, Philipp Kolb, Haizhang Chen, Ivana Andreeva, Theresa Tretter, Hanns‐Martin Lorenz, Carsten Watzl, Guido Wabnitz, Lars‐Oliver Tykocinski, Wolfgang Merkt
Journal: Arthritis & Rheumatology (2021)

Objective Findings from recent transcriptome analyses of the synovium of patients with rheumatoid arthritis (RA) have revealed that 15‐fold expanded HLA–DR+CD90+ synovial fibroblasts potentially act as key mediators of inflammation. The reasons for the expansion of HLA–DR+CD90+ synovial fibroblasts are unclear, but genetic signatures indicate that interferon‐γ (IFNγ) plays a central role in the generation of this fibroblast subset. The present study was undertaken to investigate the generation, function and therapeutically intended blockage of HLA–DR+CD90+ synovial fibroblasts. Methods We combined functional assays using primary human materials and focused bioinformatic analyses of mass cytometry and transcriptomics patient data sets. Results We detected enriched and activated Fcγ receptor type IIIa–positive (CD16+) NK cells in the synovial tissue from patients with active RA. Soluble immune complexes were recognized by CD16 in a newly described reporter cell model, a mechanism that could be contributing to the activation of natural killer (NK) cells in RA. In vitro, NK cell–derived IFNγ induced HLA–DR on CD90+ synovial fibroblasts, leading to an inflammatory, cytokine‐secreting HLA–DR+CD90+ phenotype. HLA–DR+CD90+ synovial fibroblasts consecutively activated CD4+ T cells upon receptor crosslinking via superantigens. HLA–DR+CD90+ synovial fibroblasts also activated CD4+ T cells in the absence of superantigens, an effect that was initiated by NK cell–derived IFNγ and that was 4 times stronger in patients with RA compared to patients with osteoarthritis. Finally, JAK inhibition in synovial fibroblasts prevented HLA–DR induction and blocked proinflammatory signals to T cells. Conclusion The HLA–DR+CD90+ phenotype represents an activation state of synovial fibroblasts during the process of inflammation in RA that can be induced by IFNγ, likely generated from infiltrating leukocytes such as activated NK cells. The induction of these proinflammatory, interleukin‐6–producing, and likely antigen‐presenting synovial fibroblasts can be targeted by JAK inhibition.
Overexpression of tissue factor in cancer cells inhibits chemotherapy-induced apoptosis by activating Bcl-2 expression through the JAK/STAT5 pathway
Authors: Jun Fang, Lubing Gu, Hao Tang, Ningxi Zhu, Carlos Alvarado, Harry Findley, Muxiang Zhou
Journal: Cancer Research (2007)

3633  Tissue factor (TF) is a transmembrane protein that acts as a receptor for activated coagulation factor VII (FVIIa), initiating the coagulation cascade. Recent studies demonstrate that expression of tumor-derived TF also mediates intracellular signaling relevant to tumor growth and metastasis. Our present study reports that overexpression of TF in cancer cells acts to upregulate Bcl-2 expression via the JAK/STAT5 pathway, resulting in enhanced cell survival and resistance to chemotherapeutic drug-induced apoptosis. Inhibition of endogenous TF expression in TF-overexpressing cancer cells using siRNA resulted in decreased cell growth and sensitization to doxorubicin-induced apoptosis. In contrast, enforced expression of TF in TF-negative cancer cells in the presence of FVIIa was found to induce upregulation of Bcl-2, leading to resistance to doxorubicin. Additionally, cancer cells expressing high levels of either endogenous or transfected TF treated with FVIIa readily activated STAT5 and Akt. Using selective pharmacologic inhibitors, we demonstrated that JAK inhibitor I, but not the PI3K inhibitor LY294002, blocked the TF/FVIIa-induced upregulation of Bcl-2. These results suggest that overexpression of TF by tumor cells ligated with FVIIa upregulate Bcl-2 expression through the JAK/STAT5 signaling pathway, resulting in resistance to apoptosis. This activity may contribute, at least in part, to tumor development and progression.
25602 Improvements and response achievement in PASI subscale domains for head scaling and erythema in apremilast-treated patients with moderate to severe plaque psoriasis of the scalp: Results from the STYLE study
Authors: Kim Papp, Abby Van Voorhees, Linda Stein Gold, Mark Lebwohl, Bruce Strober, Zuoshun Zhang, Yao Wang
Journal: Journal of the American Academy of Dermatology (2021)
Phage Therapy for Antibiotic-Resistant Bacterial Infections
Authors: Graham F. Hatfull, Rebekah M. Dedrick, Robert T. Schooley
Journal: Annual Review of Medicine (2021)

Antibiotic resistance in bacterial pathogens presents a substantial threat to the control of infectious diseases. Development of new classes of antibiotics has slowed in recent years due to pressures of cost and market profitability, and there is a strong need for new antimicrobial therapies. The therapeutic use of bacteriophages has long been considered, with numerous anecdotal reports of success. Interest in phage therapy has been renewed by recent clinical successes in case studies with personalized phage cocktails, and several clinical trials are in progress. We discuss recent progress in the therapeutic use of phages and contemplate the key factors influencing the opportunities and challenges. With strong safety profiles, the main challenges of phage therapeutics involve strain variation among clinical isolates of many pathogens, battling phage resistance, and the potential limitations of host immune responses. However, the opportunities are considerable, with the potential to enhance current antibiotic efficacy, protect newly developed antibiotics, and provide a last resort in response to complete antibiotic failure.
Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancer
Authors: Apostolia-Maria Tsimberidou, Jamie V. Shaw, Dejan Juric, Claire Verschraegen, Amy M. Weise, John Sarantopoulos, Gilberto Lopes, John Nemunaitis, Monica Mita, Haeseong Park, Barbara Ellers-Lenz, Hui Tian, Wenyuan Xiong, Remigiusz Kaleta, Razelle Kurzrock
Journal: Journal of Hematology & Oncology (2021)

The PI3K/AKT/mTOR (PAM) pathway is a key regulator of tumor therapy resistance. We investigated M2698, an oral p70S6K/AKT dual inhibitor, in patients with advanced cancer who failed standard therapies.M2698 was administered as monotherapy (escalation, 15-380 mg daily; food effect cohort, 240-320 mg daily) and combined with trastuzumab or tamoxifen.Overall, 101 patients were treated (M2698, n = 62; M2698/trastuzumab, n = 13; M2698/tamoxifen, n = 26). Patients were predominantly aged < 65 years, were female, had performance status 1 and were heavily pretreated. There was a dose- and concentration-dependent inhibition of pS6 levels in peripheral blood mononuclear cells and tumor tissue. M2698 was well tolerated; the most common treatment-emergent adverse events were gastrointestinal, abnormal dreams and fatigue (serious, attributed to M2698: monotherapy, 8.1%; M2698/trastuzumab, 7.7%; M2698/tamoxifen, 11.5% of patients). The recommended phase 2 doses of M2698 were 240 mg QD (monotherapy), 160 mg QD (M2698/trastuzumab) and 160 mg QD/240 mg intermittent regimen (M2698/tamoxifen). In the monotherapy cohort, 27.4% of patients had stable disease at 12 weeks; no objective response was noted. The median progression-free survival (PFS) durations in patients with PAM pathway alterations with and without confounding markers (KRAS, EGFR, AKT2) were 1.4 months and 2.8 months, respectively. Two patients with breast cancer (M2698/trastuzumab, n = 1; M2698/tamoxifen, n = 1) had partial response; their PFS durations were 31 months and 2.7 months, respectively.M2698 was well tolerated. Combined with trastuzumab or tamoxifen, M2698 demonstrated antitumor activity in patients with advanced breast cancer resistant to multiple standard therapies, suggesting that it could overcome treatment resistance. Trial registration ClinicalTrials.gov, NCT01971515. Registered October 23, 2013.
27582 Abrocitinib improves work productivity through improvement in pruritus and sleep: Results from the JADE MONO-2 study in patients with moderate-to-severe atopic dermatitis (AD)
Authors: Gil Yosipovitch, Mette Deleuran, John Su, Luz Fonacier, Andrew G. Bushmakin, Joseph C. Cappelleri, Claire Feeney, Andrew Thorpe, Ricardo Rojo, Hernan Valdez, Daniela E. Myers
Journal: Journal of the American Academy of Dermatology (2021)
Apples to apples? Comparative analyses of national CF registries
Authors: Lucy Mary Perrem, Paul McNally, Felix Ratjen
Journal: Thorax (2021)

National registries play a crucial role in understanding the natural history of cystic fibrosis (CF) and the impact of care delivery and interventions on outcomes. Data on more than 90 000 individuals are captured in CF registries around the world.1 Detailed examination of clinical characteristics, interventions and outcomes, benchmarking CF centres within jurisdictions and international comparisons across healthcare systems can stimulate quality improvement initiatives and drive effective changes in practice.

In a 2015 cross-sectional comparison of the US and the UK national CF registries, children in the US had better lung function than their UK counterparts2; these differences persisted into early adulthood. However, both cohort effects and survivor bias could have affected the data interpretation as outlined in an accompanying editorial.3 In this issue of the Journal , addressing some of these confounders, Schluter and colleagues4 once again compared US and UK registry data, but this time focused on longitudinal trajectories of parallel cohorts limiting the study population to children between 6 and 18 years and those homozygous for the F508del mutation. The mean difference in per cent-predicted FEV1 (ppFEV1) between the US and UK populations at ages 6, 12 and 17 years was approximately 4%, 5% and 6%, respectively. The data suggested that children in the US may also have a slower rate of lung function decline, but the evidence for this was less convincing and dependent on …
27615 Impact of body mass index (BMI) on efficacy of three topical acne treatments in patients with moderate-to-severe acne
Authors: Fran Cook-Bolden, Fran E. Cook-Bolden, Lawrence Green, Jonette Keri, Leon Kircik, Hilary Baldwin, William P. Wershchler, Eric Guenin, Varsha Bhatt, Radhakrishnan Pillai
Journal: Journal of the American Academy of Dermatology (2021)