tbuckley/cabot-search huggingface dataset:
REPLY:
Authors: Kara Wegermann, Ayako Suzuki, Alisha M. Mavis, Manal F. Abdelmalek, Anna Mae Diehl, Cynthia A. Moylan
Journal: Hepatology (2020)

Potential conflict of interest: Dr. Mavis is on the speakers' bureau for Alexion. Dr. Moylan consults for GLG and advises Gilead. We appreciate de Zegher and Ibáňez calling attention to the association between nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). As de Zegher and Ibáňez rightly point out, NAFLD can occur in children and adolescents with PCOS, with the potential for development of advanced fibrosis in early adulthood. The link between PCOS and NAFLD has been established in the literature,(1) but uniform screening and preventive strategies have not yet been developed. Interventions addressing hormonal imbalances, as described by de Zegher and Ibáňez, may thus hold potential in this population.
Left ventricular systolic ejection time is an independent predictor of all‐cause mortality in heart failure with reduced ejection fraction
Authors: Alia S. Alhakak, Morten Sengeløv, Peter G. Jørgensen, Niels E. Bruun, Cecilie Johnsen, Ulrik Abildgaard, Allan Z. Iversen, Thomas F. Hansen, John R. Teerlink, Fady I. Malik, Scott D. Solomon, Gunnar Gislason, Tor Biering‐Sørensen
Journal: European Journal of Heart Failure (2020)
Geriatric assessment-driven interventions among hospitalized older adults with cancer (GAIN-HOSP): A prospective pilot study.
Authors: Leana Chien, Can-Lan Sun, Heeyoung Kim, Carolina Uranga, Enrique Soto Perez De Celis, Peggy Burhenn, Kemeberly Charles, Jessica Vazquez, Elsa Roberts, Wai (Kim) Yu, Jae Y. Kim, Clayton Lau, Stephen Sentovich, Tanya B. Dorff, Mina S. Sedrak, Vani Katheria, Arti Hurria, William Dale, Daneng Li
Journal: Journal of Clinical Oncology (2020)

52 Background: Older adults with cancer often have age-associated vulnerabilities and challenges, especially during hospitalization. Geriatric assessment (GA) can help identify such vulnerabilities, generate recommendations, and guide the choice of interventions. Recently, GA-driven interventions have been shown to decrease chemotherapy toxicity among older adults with cancer in the outpatient setting. However, few studies have examined its role in the inpatient setting. Our purpose was to evaluate the feasibility of GA-driven interventions among hospitalized older adults with cancer. Methods: Hospitalized patients, age 75+, with a solid tumor malignancy were eligible. Each patient completed a GA while hospitalized at T1 (Timepoint 1) and one-month post discharge T2 (Timepoint 2). An Advanced Practice Nurse (APN) reviewed the T1 GA, provided targeted care utilizing GA results and implemented interventions based on predefined triggers built into the GA’s various domains. An APN also completed follow-up visits by phone at 1 week and 1 month post discharge. The primary outcome was feasibility, defined as the percentage of participants who received GA-guided interventions and was pre-specified as successful if &gt; 80% were given recommendations. A secondary outcome of the study was to capture unplanned readmissions within 1 month post discharge. Results: Between 9/19/2017 and 5/3/2019, 49 patients were eligible and 40 were enrolled, an 82% participation rate. The median age was 80.5 years (range 75-88), 58% male, 63% Non-Hispanic white, 18% Hispanic, 15% Asian, 70% &gt; a high school education, 73% married/partner, and 48% had stage IV cancer. Most common cancer types: GI (28%), GU (23%), lung (20%). All 40 patients (100%) had ≥ 1 predefined trigger in the GA generating interventions and completed ≥ 2 follow-up visits with the APN. In total, 857 interventions were recommended, and the mean number of interventions generated per patient was 11. The top 4 interventions were Occupational Therapy/Physical Therapy (n = 66), Social Work (n = 52), Nutrition (n = 39), and Pharmacy (n = 36). Overall 89% of GA-guided interventions were implemented. Unplanned hospital readmission was low with only one patient readmitted within 30 days (3%). Conclusions: Among hospitalized adults over age 75 with cancer, using GA to identify vulnerability, and provide GA-driven multidisciplinary interventions is feasible. Further studies are warranted to examine the impact of GA-driven interventions on outcomes among hospitalized older adults with cancer.
Organ-on-a-chip platforms for accelerating the evaluation of nanomedicine
Authors: Xi Chen, Yu Shrike Zhang, Xinping Zhang, Changsheng Liu
Journal: Bioactive Materials (2020)

Nanomedicine involves the use of engineered nanoscale materials in an extensive range of diagnostic and therapeutic applications and can be applied to the treatment of many diseases. Despite the rapid progress and tremendous potential of nanomedicine in the past decades, the clinical translational process is still quite slow, owing to the difficulty in understanding, evaluating, and predicting nanomaterial behaviors within the complex environment of human beings. Microfluidics-based organ-on-a-chip (Organ Chip) techniques offer a promising way to resolve these challenges. Sophisticatedly designed Organ Chip enable in vitro simulation of the in vivo microenvironments, thus providing robust platforms for evaluating nanomedicine. Herein, we review recent developments and achievements in Organ Chip models for nanomedicine evaluations, categorized into seven broad sections based on the target organ systems: respiratory, digestive, lymphatic, excretory, nervous, and vascular, as well as coverage on applications relating to cancer. We conclude by providing our perspectives on the challenges and potential future directions for applications of Organ Chip in nanomedicine.
Re-expression of DIRAS3 and p53 induces apoptosis and impaired autophagy in head and neck squamous cell carcinoma
Authors: Zhe Liu, Douglas R. Hurst, Xing Qu, Li-Guang Lu, Chen-Zhou Wu, Yu-Yu Li, Yi Li
Journal: Military Medical Research (2020)

Abstract Background p53 and DIRAS3 are tumor suppressors that are frequently silenced in tumors. In this study, we sought to determine whether the concurrent re-expression of p53 and DIRAS3 could effectively induce head and neck squamous cell carcinoma (HNSCC) cell death. Methods CAL-27 and SCC-25 cells were treated with Ad-DIRAS3 and rAd-p53 to induce re-expression of DIRAS3 and p53 respectively. The effects of DIRAS3 and p53 re-expression on the growth and apoptosis of HNSCC cells were examined by TUNEL assay, flow cytometric analysis and MTT. The effects of DIRAS3 and p53 re-expression on Akt phosphorylation, oncogene expression, and the interaction of 4E-BP1 with eIF4E were determined by real-time PCR, Western blotting and immunoprecipitation analysis. The ability of DIRAS3 and p53 re-expression to induce autophagy was evaluated by transmission electron microscopy, LC3 fluorescence microscopy and Western blotting. The effects of DIRAS3 and p53 re-expression on HNSCC growth were evaluated by using an orthotopic xenograft mouse model. Results TUNEL assay and flow cytometric analysis showed that the concurrent re-expression of DIRAS3 and p53 significantly induced apoptosis ( P &lt; 0.001). MTT and flow cytometric analysis revealed that DIRAS3 and p53 re-expression significantly inhibited proliferation and induced cell cycle arrest ( P &lt; 0.001). Mechanistically, the concurrent re-expression of DIRAS3 and p53 down-regulated signal transducer and activation of transcription 3 (STAT3) and up-regulated p21 WAF1/CIP1 and Bax ( P &lt; 0.001). DIRAS3 and p53 re-expression also inhibited Akt phosphorylation, increased the interaction of eIF4E with 4E-BP1, and reduced the expression of c-Myc, cyclin D1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal growth factor receptor (EGFR) and Bcl-2 ( P &lt; 0.001). Moreover, the concurrent re-expression of DIRAS3 and p53 increased the percentage of cells with GFP-LC3 puncta compared with that in cells treated with control adenovirus (50.00% ± 4.55% vs. 4.67% ± 1.25%, P &lt; 0.001). LC3 fluorescence microscopy and Western blotting further showed that DIRAS3 and p53 re-expression significantly promoted autophagic activity but also inhibited autophagic flux, resulting in overall impaired autophagy. Finally, the concurrent re-expression of DIRAS3 and p53 significantly decreased the tumor volume compared with the control group in a HNSCC xenograft mouse model [(3.12 ± 0.75) mm 3 vs. (189.02 ± 17.54) mm 3 , P &lt; 0.001]. Conclusions The concurrent re-expression of DIRAS3 and p53 is a more effective approach to HNSCC treatment than current treatment strategies.
Neuroanatomical substrates of generalized brain dysfunction in COVID-19
Authors: Virginia F. J. Newcombe, Lennart R. B. Spindler, Tilak Das, Stefan Winzeck, Kieren Allinson, Emmanuel A. Stamatakis, David K. Menon, Fahim Anwar, Edward Bullmore, Alasdair Coles, Jonathan Coles, Joanne Jones, Victoria Lupson, Edward Needham, James Rowe, Stephen Sawcer, Fernanda Valerio
Journal: Intensive Care Medicine (2020)
Preventing and Treating Anthracycline Cardiotoxicity: New Insights
Authors: Konrad Teodor Sawicki, Valentina Sala, Lorenzo Prever, Emilio Hirsch, Hossein Ardehali, Alessandra Ghigo
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Anthracyclines are the cornerstone of many chemotherapy regimens for a variety of cancers. Unfortunately, their use is limited by a cumulative dose-dependent cardiotoxicity. Despite more than five decades of research, the biological mechanisms underlying anthracycline cardiotoxicity are not completely understood. In this review, we discuss the incidence, risk factors, types, and pathophysiology of anthracycline cardiotoxicity, as well as methods to prevent and treat this condition. We also summarize and discuss advances made in the last decade in the comprehension of the molecular mechanisms underlying the pathology.
Chemical molecular‐based approach to overcome multidrug resistance in cancer by targeting P‐glycoprotein (P‐gp)
Authors: Hang Zhang, Haiwei Xu, Charles R. Ashby, Yehuda G. Assaraf, Zhe‐Sheng Chen, Hong‐Min Liu
Journal: Medicinal Research Reviews (2020)

Abstract Multidrug resistance (MDR) remains one of the major impediments for efficacious cancer chemotherapy. Increased efflux of multiple chemotherapeutic drugs by transmembrane ATP‐binding cassette (ABC) transporter superfamily is considered one of the primary causes for cancer MDR, in which the role of P‐glycoprotein (P‐gp/ ABCB1 ) has been most well‐established. The clinical co‐administration of P‐gp drug efflux inhibitors, in combination with anticancer drugs which are P‐gp transport substrates, was considered to be a treatment modality to surmount MDR in anticancer therapy by blocking P‐gp‐mediated multidrug efflux. Extensive attempts have been carried out to screen for sets of nontoxic, selective, and efficacious P‐gp efflux inhibitors. In this review, we highlight the recent achievements in drug design, characterization, structure–activity relationship (SAR) studies, and mechanisms of action of the newly synthetic, potent small molecules P‐gp inhibitors in the past 5 years. The development of P‐gp inhibitors will increase our knowledge of the mechanisms and functions of P‐gp‐mediated drug efflux which will benefit drug discovery and clinical cancer therapeutics where P‐gp transporter overexpression has been implicated in MDR.
Insect bites
Authors: Jane Wilcock, Clare Etherington, Kamila Hawthorne, Graham Brown
Journal: BMJ (2020)

Clinicians use a combination of clinical features and risk factors when assessing insect bites, but a lack of evidence for the diagnostic and prognostic value of these features, as well as a lack of data on outcomes, means that most practice is based on clinical experience and custom  Table 1 lists common vector-borne illness, which are most common in tropical and subtropical countries 1Table 1 Insect and tick vector-borne diseases1 Vector Disease caused Type of pathogen Mosquitoes:  Aedes Chikungunya Virus Dengue Virus Lymphatic filariasis Parasite Rift Valley fever Virus Yellow fever Virus Zika Virus  Anopheles Lymphatic filariasis Parasite Malaria Parasite  Culex Japanese encephalitis Virus Lymphatic filariasis Parasite West Nile virus Virus Blackflies Onchoceriasis (river blindness) Parasite Fleas Plague (transmitted from rats to humans) Bacteria Tungiasis Ectoparasite Lice Typhus Bacteria Louse-borne relapsing fever Bacteria Sandflies Leishmaniasis Bacteria Sandfly fever (phlebotomus fever) Virus Ticks Crimean-Congo haemorrhagic fever Virus Lyme disease Bacteria Relapsing fever (borreliosis) Bacteria Rickettsial diseases (such as spotted fever, Q fever) Bacteria Tick-borne encephalitis Bacteria Tularaemia Bacteria Triatome bugs Chagas disease (American trypanosomiasis) Parasite Tsetse flies Sleeping sickness (African trypanosomiasis) Parasite Insect bite uncertainties Incidence The exact incidence of insect bites and stings is not known as most are not reported 23 According to a study of data recorded by sentinel general practices in England and Wales, GP consultations about insect bites are 5 4/100 000 patients per week on average  In the UK, flucloxacillin prescribing rises by 33% in the summer months, although it isn't clear how much of this is prescribed for infected insect bites 7 An approach to assessing a patient with an insect bite Most insect bites are managed by the public, perhaps with use of over-the-counter drugs or with advice from community pharmacists  Flea bites on lower legs;multiple bites, each with a small surrounding area of erythema Clinical Photography / Science Photo Library If the patient saw the insect but cannot identify it, it may help to review images of common biting insects with them, for instance on the NHS website 9 Most insects that bite either do so defensively or are haematophagous (feed on blood)
Appropriately adapted properties of hot-extruded Zn–0.5Cu–xFe alloys aimed for biodegradable guided bone regeneration membrane application
Authors: Wentai Zhang, Ping Li, Gang Shen, Xiaoshan Mo, Chao Zhou, Dorothea Alexander, Frank Rupp, Jürgen Geis-Gerstorfer, Haijun Zhang, Guojiang Wan
Journal: Bioactive Materials (2020)

Appropriately adapted comprehensive mechanical properties, degradation behavior and biocompatibility are prerequisites for the application of Zn-based biodegradable implants. In this study, hot-extruded Zn-0.5Cu-xFe (x = 0.1, 0.2 and 0.4 wt%) alloys were fabricated as candidates for biodegradable materials for guided bone regeneration (GBR) membranes. The hot-extrusion process and Cu alloying were expected mostly to enhance the mechanical properties, and the Fe alloying was added mainly for regulating the degradation. The microstructure, mechanical properties and in vitro degradation behavior were systematically investigated. The ZnCuFe alloys were composed of a Zn matrix and FeZn13 phase. With increasing Fe content, a higher FeZn13 phase precipitation with larger particles was observed. Since elongation declined significantly until fracture with increasing Fe content up to 0.4 wt%, the ZnCuFe (0.2 wt%) alloy achieved a good balance between mechanical strength and ductility, with an ultimate tensile strength of 202.3 MPa and elongation at fracture of 41.2%. Moreover, the addition of Fe successfully accelerated the degradation of ZnCuFe alloys. The ZnCuFe (0.2 wt%) alloy showed relatively uniform corrosion in the long-term degradation test. Furthermore, extracts of the ZnCuFe (0.2 wt%) alloy showed no apparent cytotoxic effects against L929 fibroblasts, Saos-2 osteoblasts or TAg periosteal cells. The ZnCuFe (0.2 wt%) alloy exhibited the potential to inhibit bacterial adhesion of Streptococcus gordonii and mixed oral bacteria. Our study provides evidence that the ZnCuFe (0.2 wt%) alloy can represent a promising material for the application as a suitable GBR membrane.
Providing uninterrupted oral oncolytic therapies during the COVID-19 pandemic.
Authors: Edward Arrowsmith, Rachel L. Mitchell, Jack L. Taylor, Stephen Matthew Schleicher, Natalie R. Dickson, Stacey McCullough
Journal: Journal of Clinical Oncology (2020)

226 Background: Uninterrupted utilization of oral oncolytics is critical to maximizing safety and efficacy of cancer treatment. The COVID-19 pandemic presented numerous challenges to delivering a continuous and safe supply of oral oncolytics to patients with cancer including potential loss of insurance coverage, patient lost income making copays more difficult, remote pharmacy staffing difficulties, and logistical challenges in safely distributing drug to cancer patients. Tennessee Oncology has an in-house Specialty Pharmacy that utilizes home delivery of oral oncolytics while coordinating care with providers during changing patient situations. Methods: We analyzed patients who received an oral oncolytic from our pharmacy in two periods: January-May 2019 and January-May 2020. We compared the aggregate patient copay amounts during these periods, the number of patients who utilized copay assistance or foundational financial support. For insights on continuation we also assessed the medication possession ratios (MPR, the sum of the day’s supply for all fills of a given drug in a particular period divided by the number of days in that period) during these time periods for five of our most commonly dispensed drugs. Results: The aggregate patient copay was similar between the two time periods. A 22% increase in the utilization of copay cards indicated patient’s insurance coverage was sustained. We also observed a 12% increase in the number of patients utilizing foundation support for prescriptions filled. MPRs for five commonly dispensed oral oncolytics were unchanged during COVID-19. Conclusions: Our in-house specialty pharmacy maintained delivery of oral oncolytics during the COVID-19 pandemic. Patient cost share was contained by our pharmacy staff proactively utilizing copay cards for all eligible patients and diligently securing foundational grant support. The pharmacy interventions allowed for affordability, uninterrupted pharmacy operations, and consistent medication supply. This led to continued medication adherence. MPR for the 5 top dispensed medications was consistent in a year-on-year comparison. [Table: see text]
Adherence with dermatology consultant recommendations: A retrospective study of 417 hospital dermatology consultations
Authors: Alexander Hines, Elliott Campbell, Laura Hornback, Maria Sokola, Misty Hobbs, Perry Hooper, Jenna Yamamoto, Paran Davari, Srikanth Vangapandu, Amber Bettis, Stuart Tobin
Journal: Journal of the American Academy of Dermatology (2020)
Clinical Features and Outcomes of Pregnancy-Related Acute Aortic Dissection
Authors: Alan C. Braverman, Eric Mittauer, Kevin M. Harris, Arturo Evangelista, Reed E. Pyeritz, Derek Brinster, Lori Conklin, Toru Suzuki, Christina Fanola, Maral Ouzounian, Edward Chen, Truls Myrmel, Raffi Bekeredjian, Stuart Hutchison, Joseph Coselli, Dan Gilon, Patrick O’Gara, Melinda Davis, Eric Isselbacher, Kim Eagle
Journal: JAMA Cardiology (2020)

Women with aortopathy conditions are at risk for pregnancy-related aortic dissection, and these conditions may not be recognized until after the aortic dissection occurs.To examine the clinical characteristics, imaging features, and outcomes in women with pregnancy-related acute aortic dissection.A cohort study, comprising data from the International Registry of Acute Aortic Dissection (IRAD) (February 1, 1998, to February 28, 2018). The multicenter referral center study included 29 women with aortic dissection during pregnancy or less than 12 weeks post partum in IRAD from 1998 to 2018.Clinical features of pregnancy-related aortic dissection to be studied included underlying aortopathy, aortic size, type of aortic dissection, timing of dissection, hypertension, and previous aortic surgery.A total of 29 women (mean [SD] age, 32 [6] years) had pregnancy-related aortic dissection, representing 0.3% of all aortic dissections and 1% of aortic dissection in women in the IRAD. Among women younger than 35 years, aortic dissection was related to pregnancy in 20 of 105 women (19%). Thirteen women (45%) had type A aortic dissection, and 16 women (55%) had type B. Aortic dissection onset was known in 27 women (93%): 15 during pregnancy, 4 in the first trimester, and 11 in the third trimester; 12 were post partum, occurring a mean (SD) of 12.5 (14) days post partum. At type A aortic dissection diagnosis, the mean (SD) aortic diameters were sinus of Valsalva, 54.5 (5) mm and ascending aorta, 54.7 (6) mm. At type B aortic dissection diagnosis, the mean (SD) descending aortic diameter was 32.5 (5) mm. Twenty women (69%) had an aortopathy condition or a positive family history: 13 women (65%) with Marfan syndrome, 2 women (10%) with Loeys-Dietz syndrome, 2 women (10%) with bicuspid aortic valves, 2 women (10%) with a family history of aortic disease, and 1 woman (5%) with familial thoracic aortic aneurysm. Aortopathy was not recognized until after aortic dissection in 47% of the women. Twenty-eight women (97%) survived aortic dissection hospitalization.Aortic dissection complicating pregnancy is rare. Most pregnancy-related aortic dissection is due to an aortopathy often not diagnosed until after aortic dissection. In this study, type A aortic dissections were associated with a dilated aorta, and type B aortic dissections often were not. Recognition of underlying conditions and risks for aortic dissection may improve management of pregnancy in women with aortopathy.
Improving performance status documentation by hematology-oncology fellows.
Authors: Ana I. Velazquez Manana, Rahul Banerjee, Vanessa Elaine Kennedy, August Reich Dietrich, Amy M. Lin, Pelin Cinar
Journal: Journal of Clinical Oncology (2020)

250 Background: Accurate performance status (PS) documentation is essential as poor PS is a strong predictor of treatment-related toxicity. At our institution, a baseline chart review revealed missing PS documentation in 28% of Fellow-seen new patient visits (NPV); PS documentation as unstructured text comprised the remainder. The lack of structured PS documentation represents a missed opportunity for accurate data in registries, trial registration, and supportive care referrals. Methods: To improve standardized documentation of PS for NPV, we designed a Fellow-led quality improvement (QI) initiative over the course of 2 PDSA cycles. Specifically, we developed and implemented a structured PS smart data element tool (SDET) into our electronic medical record (EMR). PDSA cycle 1 (7/2019–11/2019) included SDET implementation and publicity using flyers &amp; emails. PDSA cycle 2 (12/2019–4/2020) incorporated individualized feedback to Fellows, biweekly email reminders, and outreach to attendings regarding our SDET. We calculated cumulative usage of our SDET for PS documentation during the 2019-2020 academic year among NPV seen by Fellows. Our aim was to assess and document PS in at least 50% of NPV seen in person. Results: During PDSA cycle 1, cumulative structured PS documentation increased from 8% to 31% (Table). Focus groups revealed that Fellows were not consistently incorporating our SDET into their note templates or were relying on attending-written templates. Over PDSA cycle 2, the cumulative structured PS documentation rate increased from 24% to 54%. Overall our cumulative documentation rate is 40%, in large part driven by cycle 1 because of a drop in NPVs and the transition to telehealth during the COVID-19 pandemic. Conclusions: Our Fellow-led QI intervention improved cumulative structured PS documentation from 8% to 40% using two rapid PDSA cycles. Our intervention highlights the importance of real-time data review and stakeholder feedback to identify ongoing challenges. Our third PDSA cycle will include expansion to all clinic providers (Fellows, attendings, and advanced-practice providers), as well as the incorporation of telehealth encounters and follow-up visits. We also hope to align our QI initiative with broader steps toward data interoperability via the ASCO-sponsored mCODE initiative. [Table: see text]