tbuckley/cabot-search huggingface dataset:
A Higher Foci Density of Interstitial Fibrosis and Tubular Atrophy Predicts Progressive CKD after a Radical Nephrectomy for Tumor
Authors: Luisa Ricaurte Archila, Aleksandar Denic, Aidan F. Mullan, Ramya Narasimhan, Marija Bogojevic, R. Houston Thompson, Bradley C. Leibovich, S. Jeson Sangaralingham, Maxwell L. Smith, Mariam P. Alexander, Andrew D. Rule
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement A higher percentage of the kidney cortex area that exhibits interstitial fibrosis/tubular atrophy (IF/TA) is a feature of poor prognosis on biopsy. This study describes IF/TA density (the number of IF/TA foci per area of cortex) and shows it predicts progressive CKD, independent of both percentage IF/TA and clinical characteristics among patients who have undergone nephrectomy. Other patterns of IF/TA and inflammation were not predictive for progressive CKD and mortality beyond percentage IF/TA and clinical characteristics. At the same percentage IF/TA, a higher IF/TA density suggests more scattered and widespread damage to the nephrons, with a worse kidney prognosis. This information may be helpful for accurate interpretation of the severity of “chronic changes” observed on a kidney biopsy. Background Chronic tubulointerstitial injury on kidney biopsy is usually quantified by the percentage of cortex with interstitial fibrosis/tubular atrophy (IF/TA). Whether other patterns of IF/TA or inflammation in the tubulointerstitium have prognostic importance beyond percentage IF/TA is unclear. Methods We obtained, stained, and digitally scanned full cortical thickness wedge sections of renal parenchyma from patients who underwent a radical nephrectomy for a tumor over 2000–2015, and morphometrically analyzed the tubulointerstitium of the cortex for percentage IF/TA, IF/TA density (foci per mm 2 cortex), percentage subcapsular IF/TA, striped IF/TA, percentage inflammation (both within and outside IF/TA regions), and percentage subcapsular inflammation. Patients were followed with visits every 6–12 months. Progressive CKD was defined as dialysis, kidney transplantation, or 40% decline from the postnephrectomy eGFR. Cox models assessed the risk of CKD or noncancer mortality with morphometric measures of tubulointerstitial injury after adjustment for the percentage IF/TA and clinical characteristics. Results Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73m 2 ), 117 progressive CKD events and 183 noncancer deaths occurred over a median 6.4 years. Higher IF/TA density predicted both progressive CKD and noncancer mortality after adjustment for percentage IF/TA and predicted progressive CKD after further adjustment for clinical characteristics. Independent of percentage IF/TA, age, and sex, higher IF/TA density correlated with lower eGFR, smaller nonsclerosed glomeruli, more global glomerulosclerosis, and smaller total cortical volume. Conclusions Higher density of IF/TA foci (a more scattered pattern with more and smaller foci) predicts higher risk of progressive CKD after radical nephrectomy compared with the same percentage of IF/TA but with fewer and larger foci.
Tolerance development in cow’s milk–allergic infants receiving amino acid–based formula: A randomized controlled trial
Authors: Pantipa Chatchatee, Anna Nowak-Wegrzyn, Lars Lange, Suwat Benjaponpitak, Kok Wee Chong, Pasuree Sangsupawanich, Marleen T.J. van Ampting, Manon M. Oude Nijhuis, Lucien F. Harthoorn, Jane E. Langford, Jan Knol, Karen Knipping, Johan Garssen, Valerie Trendelenburg, Robert Pesek, Carla M. Davis, Antonella Muraro, Mich Erlewyn-Lajeunesse, Adam T. Fox, Louise J. Michaelis, Kirsten Beyer, Lee Noimark, Gary Stiefel, Uwe Schauer, None Hamelman, Diego Peroni, None Boner
Journal: Journal of Allergy and Clinical Immunology (2021)
Doctors’ early retirement has trebled since 2008
Authors: Tom Moberly
Journal: BMJ (2021)

The number of doctors taking early retirement from the NHS has more than trebled over the past 13 years, official figures show. In 2020-21 1358 GPs and hospital doctors in England and Wales took voluntary early retirement or retired because of ill health, up from 401 in 2007-08 (fig 1).



Fig 1 
Doctors taking early retirement from NHS in England and Wales



Overall, the total number of doctors retiring rose by 21% over this period, from 2431 in 2007-08 to 2952 in 2020-21. The total number of doctors employed by the NHS in England and Wales rose by 25% over this period, from 141 000 to 176 000.

The figures were provided to The BMJ by the NHS Business Services Authority in response to a freedom of information …
Abstract 465: Medical Device Materials and Blood Pressure Alterations in Mice
Authors: Rafael Jaimes, Meredith Sherman, Adam Swiercz, Narine Muselimyan, Paul Marvar, Nikki Posnack
Journal: Circulation Research (2016)

Di-2-ethylhexyl phthalate (DEHP) is a plasticizer that is used to impart flexibility to polyvinyl chloride products. Patients have an increased exposure to phthalates through contact with DEHP-containing medical devices, including: storage bags containing blood, plasma, intravenous fluids, total parenteral nutrition, tubing associated with their administration, nasogastric tubes, enteral feeding tubes, catheters, extracorporeal membrane oxygenation (ECMO) circuits, hemodialysis tubing, respiratory masks and endotracheal tubes. Human health concerns pertaining to DEHP exposure are linked to its endocrine-disrupting properties. Accordingly, increased exposure has been associated with cancer, metabolic disturbances, reproductive and neurological disorders, and cardiovascular disease. As an example, epidemiological studies have shown a link between DEHP exposure and elevated systolic blood pressure in adolescents. Despite bans and restrictions on the use of DEHP-containing medical devices in other countries, there is currently no mandate from the Food &amp; Drug Administration for the use of DEHP-free devices and storage containers. The objective of this study was to quantify the impact of in vivo DEHP exposure on cardiovascular function; thereby, providing additional information for regulatory decisions by the scientific, medical and regulatory community. Healthy C57BL/6 male mice were implanted with radiotelemetry transmitters; briefly, the transmitter catheter was placed in the carotid artery and biopotential leads were routed subcutaneously to collect electrocardiogram (ECG) signals. After surgical recovery, pre-exposure data was collected, and thereafter, animals were exposed to 0.2 mg/g DEHP or control diet. We observed a significant increase in systolic pressure in DEHP-treated (145 + 3 mmHg) vs control animals (136 + 1 mmHg). We also detected an increase in diastolic and mean arterial pressure in DEHP-treated (119 + 5 and 132 + 3 mmHg, respectively) vs control animals (107 + 2 and 121 + 2 mmHg). Our previous reports have shown that DEHP diminishes cardiac contractility, which suggests that these effects on blood pressure are likely attributed to alterations in sympathetic tone and/or an increase in vascular resistance.
HIV-1細胞拡散の確立と崩壊を支配する原理【JST・京大機械翻訳】
Authors: M Hataye Jason, P Casazza Joseph, Best Katharine, Liang C. Jason, T Immonen Taina, R Ambrozak David, Darko Samuel, R Henry Amy, Laboune Farida, Maldarelli Frank, C Douek Daniel, W Hengartner Nicolas, Yamamoto Takuya, F Keele Brandon, S Perelson Alan, A Koup Richard
Journal: Cell Host & Microbe (2019)
心不全患者におけるN末端B型ナトリウム排利尿ペプチド前駆体の予後値の性差-韓国心不全登録(KorHF)の報告-
Authors: Kim Hack-Lyoung, Kim Myung-A, Choi Dong-Ju, Han Seongwoo, Jeon Eun-Seok, Cho Myeong-Chan, Kim Jae-Joong, Yoo Byung-Su, Shin Mi-Seung, Seong In-Whan, Ahn Youngkeun, Kang Seok-Min, Kim Young-Jo, Kim Hyung Seop, Chae Shung Chull, Oh Byung-Hee, Lee Myoung-Mook, Ryu Kyu-Hyung
Journal: Circulation (2017)
老視(Prosper)を持つインドの地方の茶労働者における生産性に対する近ガラスの提供の影響:無作為化試験【JST・京大機械翻訳】
Authors: Reddy Priya Adhisesha, Congdon Nathan, MacKenzie Graeme, Gogate Parikshit, Wen Qing, Jan Catherine, Clarke Mike, Kassalow Jordan, Gudwin Ella, O’Neill Ciaran, Jin Ling, Tang Jianjun, Bassett Ken, Cherwek David H, Ali Rahul
Journal: The Lancet Global Health (2018)
COVID-19 and indirect health implications in Africa: Impact, mitigation measures, and lessons learned for improved disease control
Authors: Seth C. Inzaule, Pascale Ondoa, Marguerite Massinga Loembe, Yenew Kebede Tebeje, Ahmed E Ogwell Ouma, John N. Nkengasong
Journal: PLoS Medicine (2021)

Coronavirus Disease 2019 (COVID-19) and the mitigation measures taken to limit its spread have significantly disrupted other essential health services in Africa.This disruption has threatened the control of major high-burden diseases such as HIV, tuberculosis (TB), and malaria as well as the prevention of maternal and child mortality.• While the 2020 WHO global reports for HIV, TB, and malaria show progress in control of these diseases in African countries, there are still significant gaps in meeting the global targets.Similarly, modeling studies predict that most African countries are unlikely to meet the Sustainable Development Goals (SDGs) 2030 targets for reductions in maternal and child mortality under the current rate of progress.• Prediction models and emerging empirical data indicate that the implemented mitigation measures against COVID-19 such as travel restrictions and lockdowns as well as the repurposing of health resources and suspension of prevention programs such as immunizations will lead to an increase in new infections and deaths, significantly reversing the gains achieved in the control of these health challenges.• A more comprehensive COVID-19 response that minimizes indirect deaths is therefore warranted in Africa.These include implementing WHO recommendations that limit contact with the clinic where possible, such as multimonths drug dispensing, self-testing, virtual platforms for case management, community-and home-based prevention, and care services such as home distribution of test kits, vaccines, treatment, and mosquito nets.• This is in addition to ensuring effective implementation of COVID-19 infection prevention and control measures in healthcare facilities including providing healthcare workers with personal protective equipment and prioritizing them for COVID-19 immunization.• There is also a need to incorporate aggressive recovery plans to reverse the lost gains in disease control efforts and put African countries back on course toward achieving the global targets.This includes leveraging on the wider COVID-19 response enablements such as the increased political will and global solidarity funding efforts to support a more comprehensive response that accounts for the indirect public health effects of the pandemic.
Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic
Authors: Mayte Sánchez van Kammen, Mirjam R. Heldner, Justine Brodard, Adrian Scutelnic, Suzanne Silvis, Verena Schroeder, Johanna A. Kremer Hovinga, Saskia Middeldorp, Marcel Levi, Sini Hiltunen, Erik Lindgren, Maryam Mansour, Antonio Arauz, Miguel A. Barboza, Susanna M. Zuurbier, Diana Aguiar de Sousa, Jose M. Ferro, Urs Fischer, Thalia S. Field, Katarina Jood, Turgut Tatlisumak, Jukka Putaala, Marcel Arnold, Jonathan M. Coutinho
Journal: JAMA (2021)

Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism.
Comparisons of Bleeding and Thromboembolic Events with Warfarin and New Oral Anticoagulants in Japanese Atrial Fibrillation Patients Receiving Antiplatelet Therapy
Authors: Ozawa Takanobu, Kuboyama Osamu, Yoshitake Takakatsu, Nomoto Hidetsugu, Hattori Eijiro, Tokunaga Takeshi, Isobe Mitsuaki
Journal: Circulation (2015)
重症下肢虚血(CLI)に対するアンギオソームに基づく膝下(BK)血管内治療(EVT)は創傷の治癒期間に影響を与える
Authors: Yamauchi Yasutaka, Miyamoto Akira, Hakamata Naohiro, Fukuda Masahiro, Akita Takako, Kuhara Ryoji, Tezuka Shingo, Shiigai Masaru
Journal: Circulation (2014)
Magnetic lipid nanovehicles synergize the controlled thermal release of chemotherapeutics with magnetic ablation while enabling non-invasive monitoring by MRI for melanoma theranostics
Authors: Lorena García-Hevia, Íñigo Casafont, Jessica Oliveira, Nuria Terán, Mónica L. Fanarraga, Juan Gallo, Manuel Bañobre-López
Journal: Bioactive Materials (2021)

Nowadays, a number of promising strategies are being developed that aim at combining diagnostic and therapeutic capabilities into clinically effective formulations. Thus, the combination of a modified release provided by an organic encapsulation and the intrinsic physico-chemical properties from an inorganic counterpart opens new perspectives in biomedical applications. Herein, a biocompatible magnetic lipid nanocomposite vehicle was developed through an efficient, green and simple method to simultaneously incorporate magnetic nanoparticles and an anticancer drug (doxorubicin) into a natural nano-matrix. The theranostic performance of the final magnetic formulation was validated in vitro and in vivo, in melanoma tumors. The systemic administration of the proposed magnetic hybrid nanocomposite carrier enhanced anti-tumoral activity through a synergistic combination of magnetic hyperthermia effects and antimitotic therapy, together with MRI reporting capability. The application of an alternating magnetic field was found to play a dual role, (i) acting as an extra layer of control (remote, on-demand) over the chemotherapy release and (ii) inducing a local thermal ablation of tumor cells. This combination of chemotherapy with thermotherapy establishes a synergistic platform for the treatment of solid malignant tumors under lower drug dosing schemes, which may realize the dual goal of reduced systemic toxicity and enhanced anti-tumoral efficacy.
Association of Initial Treatment With Antibiotics vs Surgery With Treatment Success and Disability in Subgroups of Children With Uncomplicated Appendicitis
Authors: Peter C. Minneci, Erinn M. Hade, Gregory A. Metzger, Jacqueline M. Saito, Grace Z. Mak, Katherine J. Deans, Ronald B. Hirschl, Samir Gadepalli, Michael A. Helmrath, Charles M. Leys, Thomas T. Sato, Dave R. Lal, Matthew P. Landman, Rashmi Kabre, Mary E. Fallat, Jennifer N. Cooper
Journal: JAMA (2021)

Peter C. Minneci, MD, MHSc; Justin B. Mahida, MD, MBA; Daniel L. Lodwick, MD, MS; Jason P. Sulkowski, MD; Kristine M. Nacion, MPH; Jennifer N. Cooper, PhD, MS; Erica J. Ambeba, PhD, MPH; R. Lawrence Moss, MD; Katherine J. Deans, MD, MHSc
Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis
Authors: Ewelina Rogozińska, Jahnavi Daru, Marios Nicolaides, Carmen Amezcua-Prieto, Susan Robinson, Rui Wang, Peter J Godolphin, Carlos Martín Saborido, Javier Zamora, Khalid S Khan, Shakila Thangaratinam
Journal: The Lancet Haematology (2021)
Abstract ND01: Discovery of INCB86550: A potent, orally bioavailable small molecule inhibitor of PDL1 for the treatment of cancer
Authors: Liangxing Wu
Journal: Cancer Research (2021)

Abstract Blocking the PD-(L)1 immune checkpoint axis with therapeutic antibodies has proven to be an effective treatment modality for multiple cancer histologies. Orally bioavailable small-molecule inhibitors of the PD-1/PD-L1 interaction have been highly anticipated as a promising alternative or complementary therapeutic to the monoclonal antibodies. This presentation will detail our discovery evolution that led to the discovery of a first-in-class small molecule PDL1 inhibitor INCB89550 which is currently in clinical trials for the treatment of cancer. The presentation will also detail our characterization of novel small molecule antagonists of the PD-(L)1 axis that function by inducing dimerization and subsequent internalization of the PD-L1 protein, effectively depleting the ligand from the cell membrane and preventing PD-1 activation on T cells. Citation Format: Liangxing Wu. Discovery of INCB86550: A potent, orally bioavailable small molecule inhibitor of PDL1 for the treatment of cancer [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 ND01.
Disease activity assessment in non‐radiographic axial spondyloarthritis‐ is it time to move beyond BASDAI or ASDAS ?
Authors: Debashish Mishra, B. V. Harish, Sudhish Gadde, Pradeepta S. Patro
Journal: Arthritis & Rheumatology (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Achieving global mortality reduction targets and universal health coverage: The impact of COVID-19
Authors: Wenhui Mao, Osondu Ogbuoji, David Watkins, Ipchita Bharali, Eric Nsiah-Boateng, Mohamed Mustafa Diab, Duah Dwomoh, Dean T. Jamison, Preeti Kumar, Kaci Kennedy McDade, Justice Nonvignon, Yewande Ogundeji, Fan-Gang Zeng, Armand Zimmerman, Gavin Yamey
Journal: PLoS Medicine (2021)

The Coronavirus Disease 2019 (CAU : PleasenotethatCOVID À 19hasbeendefinedasCoronavirusD OVID-19) pandemic threatens progress toward a "grand convergence" in global health-universal reduction in deaths from infections and maternal and child health conditions to low levels-and toward achieving universal health coverage (UHC).• Our analysis suggests that COVID-19 will exacerbate the difficulty of achieving grand convergence targets for tuberculosis (TAU : PleasenotethattheabbreviationTBhasbeenintroducedfo B), maternal mortality, and, probably, for under-5 mortality.HIV targets are likely to be met.• By 2035, our analysis suggests that the public sectors of low-income countries (LICs) would only be able to finance about a third of the costs of a package of 120 essential nAU : Pleasenotethatallinstancesof non À COVIDhavebeenreplacedwithnon À COVID À 19throug on-COVID-19 health interventions through domestic sources, unless the country increases significantly the priority assigned to the health sector; lower middle-income countries (LMICs) would likewise only be able to finance a little less than half.• The likelihood of getting back on track for reaching grand convergence and UHC will depend on (i) how quickly COVID-19 vaccines can be deployed in LICs and LMICs;(ii) how much additional public sector health financing can be mobilized from external and domestic sources; and (iii) whether countries can rapidly strengthen and focus their health delivery systems.
Abstract 395: Voluntary Exercise Enhances Cardiac Growth in Response to Chronic β-Adrenergic Receptor Stimulation
Authors: Stephen W Luckey, Nathan McLaughlin, Sherilynn Soo
Journal: Circulation Research (2016)

Exercise training protects the heart against the adverse effects of cardiovascular disease. Recent studies have identified a number of cardiac adaptations including the activation of hypertrophic signaling pathways unique to exercise. However, the underlying mechanisms by which exercise confers cardioprotection are not entirely understood. This study aims to fill this gap by examining the role of voluntary exercise in the context of chronic β-adrenergic receptor stimulation. To do this, we developed a novel experimental model in which nine-week-old female and male CB6F1 hybrid mice were subjected to 5 weeks of voluntary wheel running (EX) or housed under sedentary conditions (SED). For the final two weeks, mice were administered either vehicle (VEH) or isoproterenol (ISO, 30mg/kg/day) via an osmotic pump. As expected, we found that ISO significantly increased heart size in sedentary females and males (SED+ISO) compared to sedentary mice receiving VEH (SED+VEH). Consistent with previously published data, exercise capacity was also greater in females compared to males with regards to running duration and distance regardless of the experimental group. While exercise capacity was not affected by the administration of VEH, mice receiving ISO (EX+ISO) exercised significantly less. Cardiac growth in EX+VEH mice was significantly increased in both females and males compared to their respective SED+VEH counterparts. Importantly, EX+ISO females and males have significantly larger hearts than their respective SED+ISO cohorts. Moreover, EX+ISO mice also exhibited greater increases in cardiac size as compared to their respective EX+VEH counterparts. Thus, we conclude that there appears to be an additive effect of voluntary exercise and ISO administration in both females and males in terms of cardiac growth. These preliminary data are in contrast to previously published data which found that controlled exercise programs reduced cardiac hypertrophy under conditions of chronic β-adrenergic receptor stimulation. We are currently investigating the processes that lead to the larger heart sizes in the EX+ISO mice and aim to better understand the underlying mechanisms of exercise-mediated cardioprotection.
Multistage-responsive nanovehicle to improve tumor penetration for dual-modality imaging-guided photodynamic-immunotherapy
Authors: Yi Feng, Xiaoxue Xie, Hanxi Zhang, Qingqing Su, Geng Yang, Xiaodan Wei, Ningxi Li, Tingting Li, Xiang Qin, Shun Li, Chunhui Wu, Chuan Zheng, Jie Zhu, Fengming You, Guixue Wang, Hong Yang, Yiyao Liu
Journal: Biomaterials (2021)
Increased Risk of Incident Heart Failure and Death Is Associated With Insulin Resistance in People With Newly Diagnosed Type 2 Diabetes: UKPDS 89
Authors: Malgorzata Wamil, Ruth L. Coleman, Amanda I. Adler, John J.V. McMurray, Rury R. Holman
Journal: Diabetes Care (2021)

Insulin resistance (IR) may mediate heart failure (HF) development. We examined whether IR in people with newly diagnosed type 2 diabetes (T2D) increased their risk of a composite outcome of HF or death or of HF alone.Insulin resistance (HOMA2-IR) values for UKPDS participants were derived from paired fasting plasma glucose (FPG) and insulin measures. Kaplan-Meier survival curves and multivariable survival models were used to evaluate associations between HOMA2-IR and HF/death or HF alone. We adjusted for potential confounders by including variables with univariate associations (P < 0.1) and by requiring a multivariable P < 0.05.Of 5,102 UKPDS participants with newly diagnosed T2D, 4,344 had HOMA2-IR measurements. At enrollment, mean (SD) age was 52.5 (8.7) years, with HbA1c 7.2% (1.8%), and BMI 28.8 (5.5) kg/m2, and median (interquartile range) HOMA2-IR was 1.6 (1.1-2.2). HF/death occurred in 1,974 (45.4%) participants (235 first HF events, 1,739 deaths) over a median follow-up of 16.4 years. Multivariable independent associations with HF/death were older age and higher BMI, HOMA2-IR, FPG, waist-to-hip ratio, systolic blood pressure, LDL cholesterol, and heart rate as well as sex, race, smoking status, prior atrial fibrillation, and prior microalbuminuria. A doubling of HOMA2-IR was associated with a 5% greater risk of HF/death (relative risk [RR] 1.05 [95% CI 1.01-1.12], P = 0.0029) and a 14% greater risk of HF (RR 1.14, [95% CI 1.02-1.27], P = 0.017).Patients with newly diagnosed T2D and insulin resistance were more likely to develop HF or die than those more sensitive to insulin.
Another COVID-19 Fallout: Teens’ Happy Hour With Parents
Authors: Anita Slomski
Journal: JAMA (2021)

US Preventive Services Task Force; Susan J. Curry, PhD; Alex H. Krist, MD, MPH; Douglas K. Owens, MD, MS; Michael J. Barry, MD; Aaron B. Caughey, MD, PhD; Karina W. Davidson, PhD, MASc; Chyke A. Doubeni, MD, MPH; John W. Epling Jr, MD, MSEd; Alex R. Kemper, MD, MPH, MS; Martha Kubik, PhD, RN; C. Seth Landefeld, MD; Carol M. Mangione, MD, MSPH; Michael Silverstein, MD, MPH; Melissa A. Simon, MD, MPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD