bluuebunny/crossref_metadata_2025_split huggingface dataset:
SapC-DOPS – a Phosphatidylserine-targeted Nanovesicle for selective Cancer therapy
Authors: N’Guessan Kombo F. , Patel Priyankaben H. , Qi Xiaoyang 
Published: January 2020

AbstractPhosphatidylserine (PS) is normally located in the inner leaflet of the membrane bilayer of healthy cells, however it is expressed at high levels on the surface of cancer cells. This has allowed for the development of selective therapeutic agents against cancer cells (without affecting healthy cells). SapC-DOPS is a PS-targeting nanovesicle which effectively targets and kills several cancer types including pancreatic, lung, brain, and pediatric tumors. Our studies have demonstrated that SapC-DOPS selectively induces apoptotic cell death in malignant and metastatic cells, whereas untransformed cells remain unaffected due to low surface PS expression. Furthermore, SapC-DOPS can be used in combination with standard therapies such as irradiation and chemotherapeutic drugs to significantly enhance the antitumor efficacy of these treatments. While the PS-targeting nanovesicles are a promising selective therapeutic option for the treatment of cancers, more preclinical studies are needed to fully understand the mechanisms leading to non-apoptotic PS expression on the surface of viable cancer cells and to determine the effectiveness of SapC-DOPS in advanced metastatic disease. In addition, the completion of clinical studies will determine therapeutic effects and drug safety in patients. A phase I clinical trial using SapC-DOPS has been completed on patients with solid tumors and has demonstrated compelling patient outcomes with a strong safety profile. Results from this study are informing future studies with SapC-DOPS.
Graphical abstract
Cocaine and amphetamine-regulated transcript prepropeptide gene (CARTPT) polymorphism interacts with Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI) to affect hypothalamic hormones and cardio-metabolic risk factors among obese individuals
Authors: Mahmoudi-Nezhad Mahsa , Farhangi Mahdieh Abbasalizad , Kahroba Houman 
Published: January 2020

Abstract
Background
Epidemiologic studies show that cocaine- and amphetamine-regulated transcript prepropeptide (CARTPT) gene polymorphism modifies diet-obesity relationships. However, the interaction between CARTPT gene polymorphism and diet quality indices have not been investigated yet. The current study was aimed to evaluate the interaction between major dietary indices including Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI)-2015 and CARTPT gene rs2239670 variants among apparently healthy obese Iranians.

Methods
This cross-sectional study was carried out by employing 288 apparently healthy obese adults aged 20–50 years with a BMI of 30–40 kg/m2. Diet quality was evaluated by Diet Quality Index-International (DQI-I) and Healthy Eating Index-2015 (HEI-2015) using a 132-items semi-quantitative validated food frequency questionnaire. The CARTPT gene rs2239670 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) technique. Blood concentrations of glycemic markers, lipid profile, α-melanocyte stimulating hormone (MSH) and agouti-related peptide (AgRP) were also measured. ANCOVA multivariate interaction model was used to analyze gene-diet interactions.

Results
The significant interactions were identified between CARTPT gene polymorphism and HEI, affecting BMR (PInteraction = 0.003), serum glucose (PInteraction = 0.009) and high density lipoprotein cholesterol HDL concentrations (PInteraction = 0.03) after adjusting for the effects of sex and age. Also we found gene-diet interaction between CARTPT genotypes and DQI-I in terms of fat mass (FM; PInteraction = 0.02), waist circumference (WC; PInteraction < 0.001), body mass index (BMI; PInteraction < 0.001), basal metabolic rate (BMR, PInteraction < 0.001), serum fasting glucose (PInteraction < 0.01) and AgRP (PInteraction = 0.05) in individuals even after adjusting for potential confounders.

Conclusion
Current study showed the effects of interaction between CARTPT genotype with adherence to HEI and DQI-I scores on obesity-related anthropometric and metabolic risk-factors.
Longitudinal within-host evolution of HIV Nef-mediated CD4, HLA and SERINC5 downregulation activity: a case study
Authors: Sudderuddin Hanwei , Kinloch Natalie N. , Jin Steven W. , Miller Rachel L. , Jones Bradley R. , Brumme Chanson J. , Joy Jeffrey B. , Brockman Mark A. , Brumme Zabrina L. 
Published: January 2020

AbstractThe HIV accessory protein Nef downregulates the viral entry receptor CD4, the Human Leukocyte Antigen (HLA)-A and -B molecules, the Serine incorporator 5 (SERINC5) protein and other molecules from the infected cell surface, thereby promoting viral infectivity, replication and immune evasion. Theneflocus also represents one of the most genetically variable regions in the HIV genome, andnefsequences undergo substantial evolution within a single individual over the course of infection. Few studies however have simultaneously characterized the impact of within-hostnefsequence evolution on Nef protein function over prolonged timescales. Here, we isolated 50 unique Nef clones by single-genome amplification over an 11-year period from the plasma of an individual who was largely naïve to antiretroviral treatment during this time. Together, these clones harbored nonsynonymous substitutions at 13% ofnef’s codons. We assessed their ability to downregulate cell-surface CD4, HLA and SERINC5 and observed that all three Nef functions declined modestly over time, where the reductions in CD4 and HLA downregulation (an average of 0.6% and 2.0% per year, respectively) achieved statistical significance. The results from this case study support all three Nef activities as being important to maintain throughout untreated HIV infection, but nevertheless suggest that, despitenef’s mutational plasticity, within-host viral evolution can compromise Nef function, albeit modestly, over prolonged periods.
Patent foramen ovale closure by using transesophageal echocardiography for cryptogenic stroke: single center experience in 132 consecutive patients
Authors: Han Yangyang , Zhang Xiquan , Zhang Fengwei 
Published: January 2020

Abstract
Background
Percutaneous closure of patent foramen ovale (PFO) is routinely performed using plain fluoroscopy in the catheter room. This method results in inevitable radiation damage, adverse effects of contrast agents on kidneys, and high cost. We performed PFO closure with a simplified and economical transesophageal echocardiography (TEE)-only guided approach in the operating room. This study aimed to investigate the feasibility, safety, and effectiveness of the percutaneous closure of PFO by only using TEE.

Methods
We reviewed the medical records of patients who underwent percutaneous PFO closure at our center from December 2013 to December 2017. A total of 132 patients with PFO and cryptogenic strokes underwent PFO closure by using cardi-O-fix PFO device under TEE guidance. The participants comprised 64 and 68 male and female patients, respectively. The mean age and body weight of the patients were 39.40 ± 13.22 years old (12–68 years old) and 65.42 ± 9.70 kg (40–95 kg), respectively. All patients only received aspirin (3–5 mg/kg body weight, oral administration) for 6 months. Contrast-enhanced transthoracic echocardiography (c-TTE) with Valsalva maneuver was performed during follow-up, and questionnaire surveys were obtained at 3, 6, and 12 months after the procedure.

Results
All (100%) patients were successfully closed. Follow-ups were conducted for 13 months to 48 months, with an average of 27 months. No severe complications were found during the follow-up period. Paroxysmal atrial fibrillation occurred in 4 patients within 3 months after the procedure. No recurrent stroke or death occurred in all patients during the follow-up period. Transient ischemic attack occurred in one patient 6 months after the procedure. Ten (7.6%) patients had a right-to-left shunt, as demonstrated by c-TTE at 12 months of follow-up. Among the 57 patients suffering from migraine, significant relief or resolution was reported by 42 (73.7%) patients.

Conclusion
TEE-only guided PFO closure was a safe, feasible, and effective method that did not require the use of X-rays and contrast agents.
A modified axillo-femoral perfusion for acute type a aortic dissection accompanied with lower limb malperfusion
Authors: Li Qianzhen , Chen Liangwan , Shen Yue , Li Jiahui , Dong Yi 
Published: January 2020

Abstract
Background
Lower limb malperfusion accompanied with acute type A dissection (AAD) is reported to be an independent predictor for mortality. Timely treatment is required. However, staged approach to restore the perfusion of the ischemic leg before aortic repair has a continuously increase risk of aortic rupture. Aortic repair under isolated axillary artery perfusion also has the risk of prolonging leg ischemia. Here we introduce our experience in performing axillo-femoral perfusion, which is supposed to bring benefits for treating lower limb malperfuison.

Methods
Thirty patients who suffered AAD accompanied by lower limb ischemia enrolled in our study. All patients received aortic repair as soon as possible using the modified axillo-femoral perfusion approach. The cardiopulmonary bypass and cooling started with the right axillary artery perfusion. Then the femoral artery of the ischemic side was exposed and sewn to a graft connected with another inflow cannula. The rectal temperature was about 31 °C when the femoral perfusion started. The perfusion of the ischemic legs preoperative was estimated after the surgery by the clinical signs, the saturation of the distal-limb, and computed tomography scan.

Results
Twenty-eight patients got good perfusion of the lower body after the surgery. Two patients received femoral-femoral artery bypass immediately after surgery because of the thrombosis in the right common iliac artery, without further injury. No peripheral vessels damage occurred, and no compartment fasciotomy or amputation needed. One patient died for the sepsis and the subsequent multi organ failure 28 days postoperative.

Conclusions
The modified axllio-femoral perfusion could restore the lower limbs’ perfusion simultaneously during the aortic surgery without neither delaying dissection repair nor prolonging the ischemic time. It is a simple, but safe and effective technique.
Prevalence of Salmonella serovars isolated from reptiles in Norwegian zoos
Authors: Bjelland Ane Mohn , Sandvik Lena Maria , Skarstein Marianne Muri , Svendal Linn , Debenham John James 
Published: January 2020

AbstractBackgroundReptiles are known to be asymptomatic carriers ofSalmonellaspp. in their gastrointestinal mucosa and a variety ofSalmonellaserovars including exotic serovars mainly associated with reptiles as well as human pathogenic serovars have been isolated. There are many case reports of reptile-associatedSalmonellainfections worldwide, including one case in Norway in 2000. In August 2017, there was a legislative change in Norway that allowed more permissive reptile ownership and legalized the keeping of 19 different reptile species by private persons. There has been a concern that this new legislation will lead to an increase in reptile-associated salmonellosis in Norway, however knowledge is lacking on the occurrence ofSalmonellaspp. in Norwegian reptiles. The aim of this study was therefore to investigate the prevalence ofSalmonellaspp. in captive reptile species in Norway, identify the serovars and evaluate their zoonotic potential. Thus, cloacal swabs were taken from 53 snakes, 15 lizards and 35 chelonians from three Norwegian zoos, and assessed for the presence ofSalmonellaspp. by culture, biochemical testing and serotyping.ResultsIn total, 43% of the reptiles were sheddingSalmonellaspp., with a prevalence of 62%, 67% and 3% in snakes, lizards and chelonians, respectively. A total of 26 different serovars were found, includingSalmonella entericaspp.enterica(40%) andS. entericaspp.arizonae(4%), both of which are considered to have a high zoonotic potential.S. entericaspp.diarizonae, salamaeandhoutenaewere also identified, however these serovars are considered to have a lower zoonotic potential.ConclusionsThe current study demonstrates that captive Norwegian reptiles are carriers of potentially zoonoticSalmonellaspp. Given the increasing popularity of reptiles as pets and the legislative change, reptile-associated salmonellosis could become an increasingly important public health concern in Norway. Adequate public information about the risk ofSalmonellainfection as well as preventive measures to avoidSalmonellatransmission from reptiles to humans is needed. The risk ofSalmonellainfection is considered low when recommended precautions are taken and good hygiene exhibited.
A novel urinary biomarker predicts 1-year mortality after discharge from intensive care
Authors:   The French and European Outcome Registry in Intensive Care Unit Investigators, Nkuipou-Kenfack Esther , Latosinska Agnieszka , Yang Wen-Yi , Fournier Marie-Céline , Blet Alice , Mujaj Blerim , Thijs Lutgarde , Feliot Elodie , Gayat Etienne , Mischak Harald , Staessen Jan A. , Mebazaa Alexandre , Zhang Zhen-Yu 
Published: January 2020

Abstract
Rationale
The urinary proteome reflects molecular drivers of disease.

Objectives
To construct a urinary proteomic biomarker predicting 1-year post-ICU mortality.

Methods
In 1243 patients, the urinary proteome was measured on ICU admission, using capillary electrophoresis coupled with mass spectrometry along with clinical variables, circulating biomarkers (BNP, hsTnT, active ADM, and NGAL), and urinary albumin. Methods included support vector modeling to construct the classifier, Cox regression, the integrated discrimination (IDI), and net reclassification (NRI) improvement, and area under the curve (AUC) to assess predictive accuracy, and Proteasix and protein-proteome interactome analyses.

Measurements and main results
In the discovery (deaths/survivors, 70/299) and test (175/699) datasets, the new classifier ACM128, mainly consisting of collagen fragments, yielding AUCs of 0.755 (95% CI, 0.708–0.798) and 0.688 (0.656–0.719), respectively. While accounting for study site and clinical risk factors, hazard ratios in 1243 patients were 2.41 (2.00–2.91) for ACM128 (+ 1 SD), 1.24 (1.16–1.32) for the Charlson Comorbidity Index (+ 1 point), and ≥ 1.19 (P ≤ 0.022) for other biomarkers (+ 1 SD). ACM128 improved (P ≤ 0.0001) IDI (≥ + 0.50), NRI (≥ + 53.7), and AUC (≥ + 0.037) over and beyond clinical risk indicators and other biomarkers. Interactome mapping, using parental proteins derived from sequenced peptides included in ACM128 and in silico predicted proteases, including/excluding urinary collagen fragments (63/35 peptides), revealed as top molecular pathways protein digestion and absorption, lysosomal activity, and apoptosis.

Conclusions
The urinary proteomic classifier ACM128 predicts the 1-year post-ICU mortality over and beyond clinical risk factors and other biomarkers and revealed molecular pathways potentially contributing to a fatal outcome.
Evaluation of the safety and tolerability of a nutritional Formulation in patients with ANgelman Syndrome (FANS): study protocol for a randomized controlled trial
Authors: Herber Donna L. , Weeber Edwin J. , D’Agostino Dominic P. , Duis Jessica 
Published: January 2020

AbstractBackgroundKetogenic and low-glycemic-index diets are effective in treating drug-resistant seizures in children with Angelman syndrome. Cognition, mobility, sleep, and gastrointestinal health are intrinsically linked to seizure activity and overall quality of life. Ketogenic and low-glycemic diets restrict carbohydrate consumption and stabilize blood glucose levels. The ketogenic diet induces ketosis, a metabolic state where ketone bodies are preferentially used for fuel. The use of exogenous ketones in promoting ketosis in Angelman syndrome has not been previously studied. The study formulation evaluated herein contains the exogenous ketone beta-hydroxybutyrate to rapidly shift the body towards ketosis, resulting in enhanced metabolic efficiency.Methods/designThis is a 16-week, randomized, double-blind, placebo-controlled, crossover study to assess the safety and tolerability of a nutritional formula containing exogenous ketones. It also examines the potential for exogenous ketones to improve the patient’s nutritional status which can impact the physiologic, symptomatic, and health outcome liabilities of living with Angelman syndrome.DiscussionThis manuscript outlines the rationale for a study designed to be the first to provide data on nutritional approaches for patients with Angelman syndrome using exogenous ketones.Trial registrationClinicalTrials.gov, ID: NCT03644693. Registered on 23 August 2018. Last updated on 23 August 2018.
hUCMSC-extracellular vesicles downregulated hepatic stellate cell activation and reduced liver injury in S. japonicum-infected mice
Authors: Dong Liyang , Pu Yanan , Chen Xiaojun , Qi Xin , Zhang Lina , Xu Lei , Li Wei , Ma Yongbin , Zhou Sha , Zhu Jifeng , Li Yalin , Wang Xuefeng , Su Chuan 
Published: January 2020

Abstract
Background
Accumulating evidence shows that mesenchymal stem cells (MSCs) have the potential as a cellular therapy avenue for schistosome-induced liver injury. Extracellular vesicles (EVs) are membranous vesicles released by almost all cell types, and EVs produced by MSCs (MSC-EVs) exert therapeutic effects in several disease models. However, the potential of MSC-EVs in schistosomiasis treatment remains unclear.

Methods
Using survival analysis, HE and Masson’s trichrome staining, immunohistochemical, western blot analysis, real-time PCR, and EdU proliferation, we investigated the effects of human umbilical cord MSC-derived EVs (hUCMSC-EVs) on the survival and liver injury in the S. japonicum-infected mice and explored the underlying mechanism.

Results
Here, we found that like hUCMSCs, hUCMSC-EVs significantly ameliorated liver injury and improved the survival of schistosome-infected mice. Indeed, the hUCMSC-EV-mediated alleviation of liver injury is associated with decreased expression of α-smooth muscle actin (α-SMA), collagen 1, and collagen 3. More importantly, we showed that hUCMSC-EVs directly suppressed the proliferation of LX2 (human hepatic stellate cell) in vitro. In addition, hUCMSC-EVs significantly downregulated the activation of LX2 after transforming growth factor-β1 (TGF-β1) treatment.

Conclusion
Our results provided the first evidence that hUCMSC-EVs reduced liver injury in S. japonicum-infected mice, potentially creating new avenues for the treatment of liver damage in schistosomiasis.
Sexual dysfunction and satisfaction in obsessive compulsive disorder: protocol for a systematic review and meta-analysis
Authors: Pozza Andrea , Veale David , Marazziti Donatella , Delgadillo Jaime , Albert Umberto , Grassi Giacomo , Prestia Davide , Dèttore Davide 
Published: January 2020

AbstractBackgroundObsessive compulsive disorder (OCD) is a chronic mental health condition recognized as one of the most serious causes of disability and impaired quality of life. In the literature, there is no review about sexual dysfunction and satisfaction in OCD. The current paper presents the protocol for a systematic review and meta-analysis aimed to summarize data (1) comparing the presence of sexual dysfunction between groups with OCD and non-clinical groups, (2) investigating prevalence of each one of the sexual dysfunctions in patients with OCD, (3) comparing risk for sexual dysfunction in OCD groups with the prevalence in control groups, (4) comparing sexual satisfaction between OCD groups and non-clinical groups, and (5) investigating moderators of sexual dysfunction in OCD groups as compared with control groups. Gender, age, marital status, OCD symptom severity and subtypes, comorbid depressive disorders, comorbid anxiety disorders, concurrent psychiatric medications, comorbid general medical disease, and study quality will be investigated as moderators.MethodsThe protocol is reported according to PRISMA-P guidelines. The search will be conducted by independent reviewers during the second week of December 2019 by using electronic databases (Scopus, PubMed, EMBASE, PsycINFO, CINAHL, and the Cochrane Library), by contacting the authors of the included studies to identify further data, by examining the references of the included studies, and by handsearching conference proceedings and theses/doctoral dissertations. The study quality will be independently evaluated using the Newcastle-Ottawa Quality Assessment Scale. Random-effect meta-analyses will be computed. If there is insufficient data for a specific outcome, only a systematic review will be performed.DiscussionThis review may support clinical practice highlighting the importance of the assessment of sexuality in patients with OCD and suggesting the use of therapeutic strategies dedicated to sexuality in this clinical population with the aim of improving patients’ quality of life. Potential limitations will regard the heterogeneity of the studies in terms of the instruments used to assess sexual dysfunction/satisfaction and of the definitions used to conceptualize sexual dysfunction.Systematic review registrationProspero CRD42019132264
On a class of generalized stochastic Browder mixed variational inequalities
Authors: Min Chao , Fan Fei-fei , Yang Zhao-zhong , Li Xiao-gang 
Published: January 2020

AbstractIn this paper, we introduce a class of stochastic variational inequalities generated from the Browder variational inequalities. First, the existence of solutions for these generalized stochastic Browder mixed variational inequalities (GS-BMVI) are investigated based on FKKM theorem and Aummann’s measurable selection theorem. Then the uniqueness of solution for GS-BMVI is proved based on strengthening conditions of monotonicity and convexity, the compactness and convexity of the solution sets are discussed by Minty’s technique. The results of this paper can provide a foundation for further research of a class of stochastic evolutionary problems driven by GS-BMVI.
Prioritising the development of severity distributions in burden of disease studies for countries in the European region
Authors: Wyper Grant M. A. , Grant Ian , Fletcher Eilidh , Chalmers Neil , McCartney Gerry , Stockton Diane L. 
Published: January 2020

AbstractSeverity distributions are a means of summarising the range of health loss suffered to disease which enables estimates of disease occurrence to be paired with disability weights to estimate Years Lost to Disability (YLD) in burden of disease studies. There is a lack of current data exploring severity distributions, which has led to the Global Burden of Disease (GBD) study relying on using the same severity distributions across countries and regions across the world. This is also largely true for some national studies, although there are exceptions. Recent evidence has raised concerns that severity distributions are unlikely to be generalisable as major differences arise when using country-specific data to develop severity distributions. These issues raise uncertainties over interpreting YLD estimates, particularly if they are being used to develop and influence policies and to determine priorities across diseases and populations. It is clear that GBD researchers and those carrying out national studies need to work towards ensuring that estimates are based upon country-specific data, and, if possible, that the impact of assumptions are fully tested and understood. There is a lack of strategy about if, where, and how, this could be achieved, particularly around how efforts should be prioritised. This commentary advocates and presents a possible strategic approach to better understanding how efforts may be best placed.