bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual Antagonist of cIAP/XIAP ASTX660 Sensitizes HPV− and HPV+ Head and Neck Cancers to TNFα, TRAIL, and Radiation Therapy
Authors: Xiao Roy , An Yi , Ye Wenda , Derakhshan Adeeb , Cheng Hui , Yang Xinping , Allen Clint , Chen Zhong , Schmitt Nicole C. , Van Waes Carter 
Published: July 2019

AbstractPurpose:Human papillomavirus–negative (HPV−) head and neck squamous cell carcinomas (HNSCC) harbor frequent genomic amplification of Fas-associated death domain, with or without concurrent amplification of Baculovirus inhibitor of apoptosis repeat containing (BIRC2/3) genes encoding cellular inhibitor of apoptosis proteins 1/2 (cIAP1/2). Antagonists targeting cIAP1 have been reported to enhance sensitivity of HPV−, but not HPV+ tumors, to TNF family death ligands (TNF and TRAIL) and radiation.Experimental Design: We tested a novel dual cIAP/XIAP antagonist ASTX660 in HPV+ and HPV− cell lines in combination with death ligands TNFα and TRAIL, and in preclinical xenograft models with radiation, an inducer of death ligands. The dependence of activity on TNF was examined by antibody depletion.Results:ASTX660 sensitized subsets of HPV− and HPV+ HNSCC cell lines to TNFα and TRAIL. These antitumor effects of ASTX660 are the result of both apoptosis and/or necroptosis among HPV− cells, and primarily by apoptosis (caspase 3 and caspase 8 cleavage) in HPV+ cells. ASTX660 enhanced restoration of protein expression and inhibitory activity of proapoptotic tumor suppressor TP53 in HPV+ HNSCC. Furthermore, ASTX660 combined with radiotherapy, an inducer of death ligands, significantly delayed growth of both HPV− and HPV+ human tumor xenografts, an effect attenuated by anti-TNFα pretreatment blockade.Conclusions:IAP1/XIAP antagonist, ASTX660, sensitizes HPV+ HNSCC to TNFα via a mechanism involving restoration of TP53. These findings serve to motivate further studies of dual cIAP/XIAP antagonists and future clinical trials combining these antagonists with radiotherapy to treat both HPV+ and HPV− HNSCC.
Photodynamic Therapy for the Treatment of Vertebral Metastases: A Phase I Clinical Trial
Authors: Fisher Carl , Ali Zakariya , Detsky Jay , Sahgal Arjun , David Elizabeth , Kunz Monica , Akens Margarete , Chow Edward , Whyne Cari , Burch Shane , Wilson Brian C. , Yee Albert 
Published: July 2019

Abstract

Purpose:
Vertebroplasty (VP) and balloon kyphoplasty (KP) are minimally invasive stabilization procedures for pathologic vertebral compression fractures (VCF). Concurrent administration of photodynamic therapy (PDT) as a tumor-ablative modality has yet to be studied in humans as a potential complement to improved mechanical stability that is afforded by vertebral cement augmentation (VCA).

Patients and Methods:
This first-in-human trial used a single 6 mg/m2 dose of the clinical photosensitizer Visudyne with escalating laser light doses. Following a cohort of light-only controls (n = 6), the drug and light treatment groups (n = 6 each) were 50, 100, 150, and 200 J/cm. VCA was performed within 15 minutes following PDT. Patients were clinically reviewed at 1 and 6 weeks. The primary outcome measure was safety from a neurologic perspective.

Results:
Thirty patients comprising a variety of primary tumors were treated with PDT and either KP or VP. Vertebral PDT was technically feasible and delivered in all study patients. No dose groups showed significant increases in pain as defined by the generic SF-36 as well as disease-specific EORTC-QLQ-BM22 and EORTC-QLQ-C15-PAL questionnaires. The 50 and 100 J/cm groups showed the most significant pain reduction (P &lt; 0.05). Twelve (40%) patients experienced complications during the study including 3 patients with further vertebral fracture progression by 6 weeks despite VCA. No complications were directly attributed to PDT.

Conclusions:
Using the parameters described, vertebral PDT as an adjunct to VCA is safe from a pharmaceutical and neurologic perspective. The results of this trial motivate scale-up study evaluating potential PDT efficacy in vertebral metastatic treatment.
Ubiquitin-Specific Protease 3 Promotes Glioblastoma Cell Invasion and Epithelial–Mesenchymal Transition via Stabilizing Snail
Authors: Fan Ligang , Chen Zhengxin , Wu Xiaoting , Cai Xiaomin , Feng Shuang , Lu Jiacheng , Wang Huibo , Liu Ning 
Published: July 2019

Abstract

Epithelial–mesenchymal transition (EMT) represents one of the most important events in the invasion of glioblastomas (GBM); therefore, better understanding of mechanisms that govern EMT is crucial for the treatment of GBMs. In this study, we report that the deubiquitinase ubiquitin-specific protease 3 (USP3) is significantly upregulated in GBMs and correlates with a shorter median overall and relapse-free survival. Silencing of USP3 attenuates the migration and invasion abilities of GBM cells in vitro and tumor growth in an orthotopic xenograft mouse model. Mechanistically, we identify USP3 as a bona fide deubiquitinase for Snail, a master transcription factor that promotes EMT, in GBM cells. USP3 interacts directly with Snail and stabilizes Snail via deubiquitination. Ectopic expression of Snail could largely rescue the inhibitory effects of USP3 depletion on migration, invasion, and tumor growth of GBM cells. In addition, we found that USP3 strongly correlates with Snail expression in primary human GBM samples. Overall, our findings reveal a critical USP3–Snail signaling axis in EMT and invasion, and provide an effective therapeutic approach against GBM.

Implications:
Our study establishes USP3-mediated Snail stabilization as an important mechanism underlying GBM invasion and progression, and provides a rationale for potential therapeutic interventions in the treatment of GBM.
Effect of Vitamin D Supplementation on Lipid Profile in Vitamin D-Deficient Children with Type 1 Diabetes and Dyslipidemia
Authors: Hafez Mona , Musa Noha , Abdel Atty Sahar , Ibrahem Mohamed , Abdel Wahab Nehal 
Published: July 2019

<b><i>Background:</i></b> Vitamin D (VD) was suggested to have both direct and indirect effects on modifying lipid profile in patients with diabetes through its regulatory action that increases the activity of lipoprotein lipase in adiposity. <b><i>Objectives:</i></b> To detect the relationship between serum 25-hydroxyvitamin D (25OHD) and lipid profiles in dyslipidemic T1D patients and study the effect of VD supplementation on lipid profiles of VD-deficient T1D patients. <b><i>Methods:</i></b> Fifty patients with T1D (for &#x3e;2 years) and dyslipidemia were included. 25OHD was assessed and patients were divided accordingly into 2 groups: VD sufficiency (&#x3e;30 ng/mL) and VD deficiency (VDD) or insufficiency (&#x3c;29 ng/mL) who were allocated to VD<sub>3</sub> supplementation for 4 months, then lipid profile was reevaluated in both groups. <b><i>Results:</i></b> Thirty patients had VDD, while 20 patients had VD sufficiency. There was no significant correlation between 25OHD and different study parameters (<i>p</i> &#x3e; 0.05). A significant difference was found among both groups in the family history of coronary heart disease (<i>p</i> = 0.036) and free tetraiodothyronine 4 (<i>p</i> = 0.035). After 4 months of VD supplementation in VDD group, the mean difference (at 0 and 4 months) in low-density lipoproteins (LDL) and hemoglobin A1c (HbA1c) was statistically significant (<i>p</i> = 0.02 and 0.04 respectively) between both groups. The mean basal LDL was 126.91 mg/dL in VDD group that improved to 117.13 mg/dL after 4 months of VD therapy with a mean difference of –9.7 mg/dL compared to a mean difference of –2 mg/dL in VD sufficiency group. <b><i>Conclusions:</i></b> VDD was highly prevalent in patients with T1D. There was no significant correlation between 25OHD levels and lipid profile in patients with T1D. VD supplementation for 4 months had a significant lowering effect on LDL and HbA1c.
A new species of Monandrocarpa (Ascidiacea, Styelidae) from Vanuatu I. (South Pacific Ocean)
Authors: MONNIOT FRANÇOISE 
Published: July 2019

The U.S Coral Reef Research Foundation collected by SCUBA various marine invertebrates in the islands of Vanuatu. Among them was a small bulbous ascidian settled on thin test stolons of another discrete ascidian being very similar in colour and shape. It is a new species of the genus Monandrocarpa (Styelidae) in which few species have been recorded. This genus is characterised by gonads in rows of hermaphrodite polycarps, each of them containing a single male vesicle. Other species in the same genus are discussed.
Erythrocyte size as diagnostic character for the identification of live cryptic Odontophrynus americanus and O. cordobae (Anura: Cycloramphidae)
Authors: GRENAT P. , SALAS N. E. , MARTINO A. L. 
Published: July 2019

External morphology and size do not allow a distinction between diploid Odontophrynus cordobae and tetraploid O. americanus (Beçak et al. 1967; Barrio and Pistol de Rubel 1972). In Córdoba province allopatric diploid populations are distributed to the NW and allopatric tetraploid populations to the SE. Sympatric populations would occur in the SW of the province. A diagnostic character should be found for a correct, simple and rapid distinction of the species without sacrificing individuals. Differences in erythrocyte size (ES) between diploid and tetraploid Odontophrynus were found (Rosset et al. 2006). Martino & Sinsch (2002) defined a range of erythrocyte area for O. cordobae and O. americanus but individuals were not cytogenetically studied. Rosset et al. (2006), showed cell areas from only 2 preserved museum specimens of O. cordobae.
Diurnal Forcing and Phase Locking of Gravity Waves in the Maritime Continent
Authors: Ruppert James H. , Zhang Fuqing 
Published: July 2019

Abstract
An unfiltered zonal Hovmöller depiction of rainfall in the Maritime Continent (MC) reveals remarkable spatiotemporal continuity of zonally propagating disturbances with a diurnal period, which endure over multiple days and propagate faster than the individual convective storms they coupled with. This phenomenon and its sensitivity to the Madden–Julian oscillation (MJO) during the 2011/12 Dynamics of the MJO (DYNAMO) field campaign is examined here through a well-validated, convection-permitting model simulation conducted on a large domain. We find that these disturbances are zonally propagating diurnal gravity waves excited by vigorous nocturnal mesoscale convective systems over Sumatra and Borneo. These gravity waves are diurnally phase locked: their wavelength very closely matches the distance between these two islands (~1500 km), while their particular zonal phase speed (~±17 m s−1) allows them to propagate this distance in one diurnal cycle. We therefore hypothesize that these waves are amplified by resonant interaction due to diurnal phase locking. While these zonal gravity waves decouple from convection once beyond the MC, their divergent flow signature endures well across the Indian Ocean, provoking the notion that they may influence rainfall at far remote locations. The exact controls over this zonal phase speed remain uncertain; we note, however, that it is roughly consistent with diurnal offshore-propagating modes documented previously. Further study is required to tie this down, and more generally, to understand the sensitivity of these modes to background flow strength and the geography of the MC.
Essential Ingredients to the Dynamics of Westerly Wind Bursts
Authors: Fu Minmin , Tziperman Eli 
Published: July 2019

AbstractWesterly wind bursts (WWBs) are brief, anomalously westerly winds in the tropical Pacific that play a role in the dynamics of ENSO through their forcing of ocean Kelvin waves. They have been associated with atmospheric phenomena such as tropical cyclones, the MJO, and convectively coupled Rossby waves, yet their basic mechanism is not yet well understood. We study WWBs using an aquaplanet general circulation model, and find that eastward-propagating convective heating plays a key role in the generation of model WWBs, consistent with previous studies. Furthermore, wind-induced surface heat exchange (WISHE) acts on a short time scale of about two days to dramatically amplify the model WWB winds near the peak of the event. On the other hand, it is found that radiation feedbacks (i.e., changes in the net radiative anomalies accompanying westerly wind bursts) are not essential for the development of WWBs, and act as a weak negative feedback on WWBs and their associated convection. Similarly, sensible surface heat flux anomalies are not found to have an effect on the development of model WWBs.
Seasonal Forecasting of Tropical Cyclone Landfall Using ECMWF’s System 4
Authors: Bergman Dan L. , Magnusson Linus , Nilsson Johan , Vitart Frederic 
Published: July 2019

Abstract
A method has been developed to forecast seasonal landfall risk using ensembles of cyclone tracks generated by ECMWF’s seasonal forecast system 4. The method has been applied to analyze and retrospectively forecast the landfall risk along the North American coast. The main result is that the method can be used to forecast landfall for some parts of the coast, but the skill is lower than for basinwide forecasts of activity. The rank correlations between forecasts issued on 1 May and observations are 0.6 for basinwide tropical cyclone number and 0.5 for landfall anywhere along the coast. When the forecast period is limited to the peak of the hurricane season, the landfall correlation increases to 0.6. Moreover, when the forecast issue date is pushed forward to 1 August, basinwide tropical cyclone and hurricane correlations increase to 0.7 and 0.8, respectively, whereas landfall correlations improve less. The quality of the forecasts is in line with that obtained by others.
PTSD as a consequence of past conflict experience, recent exposure to violence and economic marginalization in post-conflict contexts: A study from Nepal, Guatemala and Northern Ireland
Authors: Eide Arne H , Dyrstad Karin 
Published: July 2019

Background: Exposure to war and conflict increases the risk of mental health problems. Poor living conditions are known to negatively impact mental health. Hypothesis: It is hypothesized that exposure to negative events after armed conflict interacts with past negative experiences, socioeconomic factors and current mental health problems. Methods: A cross-sectional survey was carried out in three contexts of previous internal armed conflict: Nepal, Guatemala and Northern Ireland. Three nationally representative samples were drawn, comprising a net sample of 3,229 respondents. Results: Both recent negative events and past negative events linked to the previous conflicts were found to be associated with elevated risk of post-traumatic stress syndrome (PTSD). Economic marginalization and urban residency also contributed to current risk of PTSD. Conclusions: The results support the study hypothesis that both past and recent negative events in combination with economic marginalization contribute to explain current risk of PTSD. It is necessary both to improve living conditions more broadly and to establish and develop health services that have the capacity to screen, prevent and treat mental health problems also in poor contexts, in particular against a background of previous armed conflict.
Brain circuitry, behavior, and cognition: A randomized placebo-controlled trial of donepezil in fragile X syndrome
Authors: Bruno Jennifer L , Hosseini SM Hadi , Lightbody Amy A , Manchanda Mai K , Reiss Allan L 
Published: July 2019

Background: Fragile X syndrome, the most common inherited cause for intellectual disability, is associated with alterations in cholinergic among other neurotransmitter systems. This study investigated the effects of donepezil hydrochloride, a cholinesterase inhibitor that has potential to correct aberrant cholinergic signaling. Method: Forty-two individuals with fragile X syndrome (mean age=19.61 years) were randomized to receive 2.5–10.0 mg of donepezil ( n=20, seven females) or placebo ( n=22, eight females) per day. One individual in the active group withdrew at week 7. Outcomes included the contingency naming test, the aberrant behavior checklist, and behavior and brain activation patterns during a functional magnetic resonance imaging gaze discrimination task. Results: There were no significant differences between active and placebo groups on cognitive (contingency naming task) or behavioral (total score or subscales of the aberrant behavior checklist) outcomes. At baseline, the active and placebo groups did not differ in functional magnetic resonance imaging activation patterns during the gaze task. After 12 weeks of treatment the active group displayed reduced activation in response to the averted vs direct gaze contrast, relative to the placebo group, in the left superior frontal gyrus. Conclusions: Reduced functional brain activation for the active group may represent less arousal in response to direct eye gaze, relative to the placebo group. Change in functional magnetic resonance imaging activation patterns may serve as a more sensitive metric and predictor of response to treatment when compared to cognitive and behavioral assessments. Our results suggest that donepezil may have an impact on brain functioning, but longer term follow-up and concomitant behavioral intervention may be required to demonstrate improvement in cognition and behavior.
La gestione della terapia ipoglicemizzante nel paziente con nefropatia da diabete mellito tipo 2
Authors: Manetti Francesco 
Published: July 2019

Management of hypoglycemic therapy in patients with type 2 diabetes mellitus and nephropathy Chronic kidney disease (CKD) is constantly increasing in terms of prevalence and incidence. Subjects with impaired renal function, even if only in the presence of micro/macroalbuminuria, have an increased cardiovascular risk profile. Therefore, we must pay particular attention to the treatment of all associated risk factors. Therapy with oral hypoglycemic agents often requires modulation of drug dosage based on kidney function. Today, there are molecules available that are able not only to induce cardiovascular protection, but also to slow the progression of renal damage.
Diagnostic accuracy of office blood pressure compared to home blood pressure in patients with mild cognitive impairment and dementia
Authors: de Heus Rianne AA , Tumelaire Maxime V , Olde Rikkert Marcel GM , Claassen Jurgen AHR 
Published: July 2019

Background: Hypertension and cognitive impairment often coexist in older people. Office blood pressure measurement is a poor indicator for diagnosing hypertension in the general population. However, its diagnostic accuracy has not been substantially studied in patients with cognitive impairment. Aim: The aim of this study was to determine the proportion of misdiagnosis of hypertension in patients with mild cognitive impairment and dementia compared to no cognitive impairment, by comparing office blood pressure measurement with home blood pressure measurement. Methods: A cross-sectional study including consecutive patients visiting a memory clinic between 2014 and 2017. Home blood pressure was measured for one week according to the European guidelines. Office blood pressure was assessed during routine clinical practice. Using guideline definitions for normal blood pressure and hypertension, we investigated the proportion of disagreement between office blood pressure measurement and home blood pressure measurement. Univariable and multivariable logistic regression compared disagreement in diagnosis between patients with dementia, mild cognitive impairment and no cognitive impairment. Results: Of 213 patients (aged 73.4±9.0 years, 42% women) 82 had dementia, 65 had mild cognitive impairment and 66 had no cognitive impairment. Mean office blood pressure was 156/84±23/11 mmHg and mean home blood pressure was 139/79±16/10 mmHg. In 31% of patients, there was disagreement in hypertension diagnosis. This proportion was higher for mild cognitive impairment (38.5%) and dementia (35.4%) compared to no cognitive impairment (18.2%), with adjusted odds ratios of 3.7 (95% confidence interval 1.5–9.0), P=0.005 for mild cognitive impairment and 3.4 (1.3–8.6), P=0.011 for dementia. Conclusions: In memory clinic patients with dementia and mild cognitive impairment, the diagnostic accuracy of office blood pressure measurement is lower compared to patients without cognitive impairment. To avoid the risk of making improper treatment decisions in this vulnerable group, a diagnosis of hypertension should be based on home blood pressure measurement, not office blood pressure measurement.
Current perspectives on location of monitoring and length of stay following PPCI for ST elevation myocardial infarction
Authors: Sharkawi Musa A , McMahon Sean , Al Jabri Dania , Thompson Paul D 
Published: July 2019

Importance: There is marked variability in location of care and hospital length of stay after primary percutaneous coronary intervention for ST elevation myocardial infarction (STEMI). Observations: We performed a literature review on non-critical care monitoring and early discharge following primary percutaneous coronary intervention and describe a framework for implementation in the real world. The medical literature was searched from 1 January 1988 to 31 April 2019 using PubMed and Cochrane Central Register of Controlled Trials. Randomized clinical trials, observational studies and guideline statements were included. Available data suggest that carefully selected low-risk STEMI patients identified using Zwolle or CADILLAC risk stratification scores after primary percutaneous coronary intervention may be considered for discharge after 48 hours of hospital care. There was no increase in major adverse cardiac events, medication non-compliance or hospital readmission with this treatment strategy. There are limited data on non-critical monitoring of uncomplicated STEMI patients; however, given the low adverse events rate, this strategy is likely to be safe in selected patients and may facilitate reduced length of stay and reduce resource utilization. Conclusions and relevance: Available evidence supports the safety of early discharge after 48 hours of care and omission of critical care monitoring in carefully selected patients following primary percutaneous coronary intervention. Early risk stratification and structured discharge planning are imperative. Adoption of this treatment strategy could reduce hospital costs, resource utilization and enhance patient satisfaction without affecting outcomes.