bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive 5P framework for active aging using the ecological approach: an iterative systematic review
Authors: Lak Azadeh , Rashidghalam Parichehr , Myint Phyo K. , Baradaran Hamid R.
Published: January 2020

Background

“Active aging” is an inclusive term and has been defined from a variety of aspects in different domains throughout the literature. The aim of this review was to identify those aspects that play significant roles in building this concept using an ecological approach.

Methods

In this study, seven online databases, including JSTOR, Pub-Med, Web of Science, Google Scholar, ProQuest, EBSCO, and Scopus, were searched from 2002 to 2018 for both qualitative and quantitative articles published in English. Two reviewers independently found the related articles using the search terms “active aging” and “built environment” and included both “ageing” and “aging”.

Results

Of 1500 records which passed the screening stage, 92 were eligible for inclusion in the review. A total of 15 subthemes were derived: (1) personal characteristics, (2) behavioral attitude, (3) land use, (4) access, (5) physical form, (6) cityscape/city image, (7) public open spaces, (8) housing, (9) social environment, (10) cultural Environment, (11) economic environment, (12) good governance, (13) physical health, (14) mental health, and (15) social health. Ecological themes of active aging can be defined as the 5P model: person, processes, place, prime, and policymaking.

Conclusions

The results of this study can shed light on different aspects of active aging. Also, the results emphasized the significance of the multidimensional nature of active aging, micro (person), meso (process), and macro systems (place and policymaking), based on health (prime) environments. Moreover, the results were based on the relationships between the person and the environment at the individual, interpersonal, and environmental levels, which can be used to conduct future studies and develop policies on aging populations.
Are the MORECare guidelines on reporting of attrition in palliative care research populations appropriate? A systematic review and meta-analysis of randomised controlled trials
Authors: Oriani Anna , Dunleavy Lesley , Sharples Paul , Perez Algorta Guillermo , Preston Nancy J.
Published: January 2020

Background

Palliative care trials have higher rates of attrition. The MORECare guidance recommends applying classifications of attrition to report attrition to help interpret trial results. The guidance separates attrition into three categories: attrition due to death, illness or at random. The aim of our study is to apply the MORECare classifications on reported attrition rates in trials.

Methods

A systematic review was conducted and attrition classifications retrospectively applied. Four databases, EMBASE; Medline, CINHAL and PsychINFO, were searched for randomised controlled trials of palliative care populations from 01.01.2010 to 08.10.2016. This systematic review is part of a larger review looking at recruitment to randomised controlled trials in palliative care, from January 1990 to early October 2016. We ran random-effect models with and without moderators and descriptive statistics to calculate rates of missing data.

Results

One hundred nineteen trials showed a total attrition of 29% (95% CI 28 to 30%). We applied the MORECare classifications of attrition to the 91 papers that contained sufficient information. The main reason for attrition was attrition due to death with a weighted mean of 31.6% (SD 27.4) of attrition cases. Attrition due to illness was cited as the reason for 17.6% (SD 24.5) of participants. In 50.8% (SD 26.5) of cases, the attrition was at random. We did not observe significant differences in missing data between total attrition in non-cancer patients (26%; 95% CI 18–34%) and cancer patients (24%; 95% CI 20–29%). There was significantly more missing data in outpatients (29%; 95% CI 22–36%) than inpatients (16%; 95% CI 10–23%). We noted increased attrition in trials with longer durations.

Conclusion

Reporting the cause of attrition is useful in helping to understand trial results. Prospective reporting using the MORECare classifications should improve our understanding of future trials.
Correction to: Common ancestry of heterodimerizing TALE homeobox transcription factors across Metazoa and Archaeplastida
Authors: Joo Sunjoo , Wang Ming Hsiu , Lui Gary , Lee Jenny , Barnas Andrew , Kim Eunsoo , Sudek Sebastian , Worden Alexandra Z. , Lee Jae-Hyeok
Published: January 2020

Upon publication of the original article [1], it was noticed that Alexandra Z. Worden’s affiliation is not complete. The full affiliation information for Alexandra Z. Worden is can be found below and in the complete affiliation list of this Correction article.
Different effects of cortisol on pro-inflammatory gene expressions in LPS-, heat-killed E.coli-, or live E.coli-stimulated bovine endometrial epithelial cells
Authors: Cui Luying , Wang Yali , Wang Heng , Dong Junsheng , Li Zixiang , Li Jun , Qian Chen , Li Jianji
Published: January 2020

Background

Bacterial infections are common in postpartum dairy cows. Cortisol level has been observed to increase in dairy cows during peripartum period, and is associated with the endometrial innate immunity against pathogens like E.coli. However, the mechanism underlying how cortisol regulates E.coli-induced inflammatory response in bovine endometrial epithelial cells (BEEC) remains elusive.

Results

Cortisol decreased the expressions of IL1β, IL6, TNF-α, IL8, and TLR4 mRNA in BEEC treated with LPS or heat-killed E.coli, but up-regulated these gene expressions in BEEC stimulated by live E.coli.

Conclusion

Cortisol exerted the anti-inflammatory action on LPS- or heat-killed E.coli-stimulated BEEC, but the pro-inflammatory action on live E.coli-induced BEEC.
LINC00908 negatively regulates microRNA-483-5p to increase TSPYL5 expression and inhibit the development of prostate cancer
Authors: Fan Li , Li Hai , Zhang Yun
Published: January 2020

Background

Accumulating evidence has associated aberrant long non-coding RNAs (lncRNAs) with various human cancers. This study aimed to explore the role of LINC00908 in prostate cancer (PCa) and its possible underlying mechanisms.

Methods

Microarray data associated with PCa were obtained from the Gene Expression Omnibus (GEO) to screen the differentially expressed genes or lncRNAs. Then, the expression of LINC00908 in PCa tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The localization of LINC00908 in PCa cells was examined by fluorescence in situ hybridization (FISH). The relationship among LINC00908, microRNA (miR)-483-5p, and TSPYL5 was detected by bioinformatics analysis, dual-luciferase reporter assay, RNA pull-down, RNA binding protein immunoprecipitation (RIP), and FISH assays. Cell biological behaviors were assessed after the expression of LINC00908, miR-483-5p, and TSPYL5 was altered in PCa cells. Lastly, tumor growth in nude mice was evaluated.

Results

Poorly expressed LINC00908 was witnessed in PCa tissues and cells. LINC00908 competitively bound to miR-483-5p to up-regulate the TSPYL5 expression. Overexpression of LINC00908 resulted in reduced PCa cell proliferation, migration and invasion, and promoted apoptosis. Additionally, the suppression on PCa cell proliferation, migration and invasion was induced by up-regulation of TSPYL5 or inhibition of miR-483-5p. In addition, in vivo experiments showed that overexpression of LINC00908 inhibited tumor growth of PCa.

Conclusion

Overall, LINC00908 could competitively bind to miR-483-5p to increase the expression of TSPYL5, thereby inhibiting the progression of PCa. Therefore, LINC00908 may serve as a novel target for the treatment of PCa.
SapC-DOPS – a Phosphatidylserine-targeted Nanovesicle for selective Cancer therapy
Authors: N’Guessan Kombo F. , Patel Priyankaben H. , Qi Xiaoyang
Published: January 2020

Phosphatidylserine (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

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

The 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

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

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

Background

Reptiles 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.

Results

In 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.

Conclusions

The 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

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

Background

Ketogenic 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/design

This 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.

Discussion

This 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 registration

ClinicalTrials.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

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

Background

Obsessive 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.

Methods

The 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.

Discussion

This 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 registration

Prospero 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

In 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

Severity 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.
Role of NADPH oxidase and its therapeutic intervention in TGF-β-mediated EMT progression: an in vitro analysis on HeLa cervical cancer cells
Authors: Muthuramalingam Karthika , Cho Moonjae , Kim Youngmee
Published: January 2020

Epithelial to mesenchymal transition (EMT) is a complex biological event, wherein polarized epithelial cells lose their integrity resulting in a mesenchymal phenotype with enhanced motility, a phenomenon known as metastasis. However, the underlying mechanisms of EMT are still poorly understood in cervical carcinomas. In this study, we investigated the molecular signalling events responsible for the effect of TGF-β, a potent inducer of EMT, on HeLa cervical cancer cells. We observed that TGF-β treatment (5 ng/mL) upregulates the expression of EMT-associated transcription factors such as Snail and Slug and downregulates the expression of epithelial markers such as ZO-1 and E-cadherin. Furthermore, treatment with TGF-β activates both Smad-dependent and Smad-independent signaling pathways, which subsides upon addition of Diphenyleneiodonium (DPI), a potent ROS inhibitor that inhibits NADPH
oxidase (NOX). TGF-β treatment enhanced cellular migration and invasion ability was diminished in the presence of ROS inhibitors. In addition, we also observed that ROS-mediated, TGF-β-induced EMT progression was inhibited using therapeutic candidates that target the key signal transduction mediators, including PI3K/AKT, ERK, and P38/MAPK. Accordingly, we demonstrated the involvement of redox biology (NOX2 and NOX4 mediate migration and invasion) in TGF-β-mediated EMT advancement and explored suitable therapeutic interventions.
Severe intoxication caused by sodium-glucose cotransporter 2 inhibitor overdose: a case report
Authors: Nakamura Miho , Nakade Junya , Toyama Tadashi , Okajima Masaki , Taniguchi Takumi
Published: January 2020

Background

Sodium-glucose cotransporter 2 (SGLT2) inhibitors inhibit SGLT2, which is expressed in the proximal renal tubule, and thus reduce blood glucose levels by enabling the urinary excretion of excess glucose. SGLT2 inhibitors have been reported to suppress the complications of diabetes and reduce overall mortality. However, little is known about the types of symptoms that may occur in response to an overdose of an SGLT2 inhibitor. Here, we describe a case of intoxication caused by an overdose of an SGLT2 inhibitor.

Case presentation

An otherwise physically healthy adult woman ingested an overdose of ipragliflozin, an SGLT2 inhibitor, and a polypill of olmesartan medoxomil, and azelnidipine in a suicide attempt. Although her blood ipragliflozin concentration was very high (9516.3 ng/mL) upon hospital arrival, her initial blood glucose level was normal, and she did not exhibit symptoms such as hypoglycemia or polyuria. Moderate renal dysfunction associated with an estimated glomerular filtration rate of 42.3 mL/min/1.73 m2 was observed. Thirty-six hours after ingestion, her blood ipragliflozin concentration decreased to a level equivalent to that observed after a therapeutic dose and her renal function improved almost simultaneously. After improvement in her renal function, the osmotic diuretic effect of the drug progressed. Her blood glucose level declined slightly but was in the normal range due to glucose administration. During the clinical course, fatal hypoglycemia was not observed.

Conclusions

Our case showed that an overdose of an SGLT2 inhibitor caused toxic effects on renal function, but severe hypoglycemia was not observed. Additional cases of intoxication from SGLT2 inhibitors alone would be helpful to clarify the mechanism of intoxication.
Novel immunomodulatory drugs and neo-substrates
Authors: Gao Shaobing , Wang Shichao , Song Yongping
Published: January 2020

Thalidomide, lenalidomide and pomalidomide are immunomodulatory drugs (IMiDs) effective in the treatment of multiple myeloma, myelodysplastic syndrome (MDS) with deletion of chromosome 5q and other hematological malignancies. Recent studies showed that IMiDs bind to CRBN, a substrate receptor of CRL4 E3 ligase, to induce the ubiquitination and degradation of IKZF1 and IKZF3 in multiple myeloma cells, contributing to their anti-myeloma activity. Similarly, lenalidomide exerts therapeutic efficacy via inducing ubiquitination and degradation of CK1α in MDS with deletion of chromosome 5q. Recently, novel thalidomide analogs have been designed for better clinical efficacy, including CC-122, CC-220 and CC-885. Moreover, a number of neo-substrates of IMiDs have been discovered. Proteolysis-targeting chimeras (PROTACs) as a class of bi-functional molecules are increasingly used as a strategy to target otherwise intractable cellular protein. PROTACs appear to have broad implications for novel therapeutics. In this review, we summarized new generation of immunomodulatory compounds, their potential neo-substrates, and new strategies for the design of novel PROTAC drugs.
Towards the restoration of the Mesoamerican Biological Corridor for large mammals in Panama: comparing multi-species occupancy to movement models
Authors: Meyer Ninon F. V. , Moreno Ricardo , Reyna-Hurtado Rafael , Signer Johannes , Balkenhol Niko
Published: January 2020

Background

Habitat fragmentation is a primary driver of wildlife loss, and the establishment of biological corridors is a conservation strategy to mitigate this problem. Identifying areas with high potential functional connectivity typically relies on the assessment of landscape resistance to movement. Many modeling approaches exist to estimate resistance surfaces but to date only a handful of studies compared the outputs resulting from different methods. Moreover, as many species are threatened by fragmentation, effective biodiversity conservation requires that corridors simultaneously meet the needs of multiple species. While many corridor planning initiatives focus on single species, we here used a combination of data types and analytical approaches to identify and compare corridors for several large mammal species within the Panama portion of the Mesoamerican Biological Corridor.

Methods

We divided a large mammal assemblage into two groups depending on the species sensitivity to habitat disturbance. We subsequently used cost-distance methods to produce multi-species corridors which were modeled on the basis of (i) occupancy of nine species derived from camera trapping data collected across Panama, and (ii) step selection functions based on GPS telemetry data from white-lipped peccary Tayassu pecari, puma Puma concolor, and ocelot Leopardus pardalis. In addition to different data sources and species groups, we also used different transformation curves to convert occupancy and step-selection results into landscape resistance values.

Results

Corridors modeled differed between sensitive and tolerant species, between the data sets, and between the transformation curves. There were more corridors identified for tolerant species than for sensitive species. For tolerant species, several corridors developed with occupancy data overlapped with corridors produced with step selection functions, but this was not the case for sensitive species.

Conclusion

Our study represents the first comparison of multispecies corridors parametrized with step selection functions versus occupancy models. Given the wide variability in output corridors, our findings underscore the need to consider the ecological requirements of several species. Our results also suggest that occupancy models can be used for estimating connectivity of generalist species. Finally, this effort allowed to identify important corridors within the MBC (i) at a country scale and (ii) for several species simultaneously to accurately inform the local authorities in conservation planning. The approach we present is reproducible in other sites and/or for other species.
Patients suffering from psychological impairments following critical illness are in need of information
Authors: Vlake Johan H. , van Genderen Michel E. , Schut Anna , Verkade Martijn , Wils Evert-Jan , Gommers Diederik , van Bommel Jasper
Published: January 2020

Background

Because critical illness survivors frequently experience several long-term psychological impairments altering quality of life after ICU, there is a trend towards increasing follow-up care, mainly via ICU follow-up clinics. Despite these and other initiatives, understanding of patient’s post-ICU needs to help them cope with their problems and subsequently improve quality of life is largely lacking. Our aim was therefore to assess the needs, expectations and wishes in ICU survivors to receive information with the purpose to help them better grasp ICU treatment. In addition, we assessed the perceived burden of psychological trauma after ICU treatment and the health-related quality of life (HRQoL) up to 2.5 years after ICU discharge.

Methods

In a multicentre, retrospective cross-sectional cohort study, the needs and preferred intervention methods were assessed using a self-composed inventory in adult mechanically ventilated ICU survivors (n = 43). Additionally, the Impact of Event Scale Revised, the Beck Depression Inventory, the EuroQol-5D-5L, and the Short-Form 12 were used to assess psychological burden and HRQoL.

Results

A substantial proportion of all ICU survivors (59%, 95% CI 44% to 74%) suffered from psychological impairments after ICU treatment. Seventy-five percent of these patients expressed a wish to receive information, but only 36% desired to receive this information using a commonly used information brochure. In contrast, 71% of these patients had a wish to receive information using a video film/VR. Furthermore, only 33% of these patients was satisfied with the information provided by their treating hospital. Patients with psychological PICS reported a worse HRQoL as compared to a normative Dutch sample (P < 0.001) and as compared to patients without psychological PICS (P < 0.01).

Conclusions

In a Dutch cohort of critical illness survivors, a substantial part of ICU survivors suffer from psychological impairments, such as PTSD and depression, which was associated with a worse HRQoL. These patients are in need of information, have no desire using an information brochure, but are willing to receive information using a video film/virtual reality module. These results support the exploration of such an intervention.
Carbon monoxide in intensive care medicine—time to start the therapeutic application?!
Authors: Goebel Ulrich , Wollborn Jakob
Published: January 2020

Carbon monoxide (CO) is not only known as a toxic gas due to its characteristics as an odorless molecule and its rapid binding to haem-containing molecules, thus inhibiting the respiratory chain in cells resulting in hypoxia. For decades, scientists established evidence about its endogenously production in the breakdown of haem via haem-oxygenase (HO-1) and its physiological effects. Among these, the modulation of various systems inside the body are well described (e.g., anti-inflammatory, anti-oxidative, anti-apoptotic, and anti-proliferative). Carbon monoxide is able to modulate several extra- and intra-cellular signaling molecules leading to differentiated response according to the specific stimulus. With our growing understanding in the way CO exerts its effects, especially in the mitochondria and its intracellular pathways, it is tempting to speculate about a clinical application of this substance. Since HO-1 is not easy to induce, research focused on the application of the gaseous molecule CO by itself or the implementation of carbon monoxide releasing molecules (CO-RM) to deliver the molecule at a time- and dose dependently safe way to any target organ. After years of research in cellular systems and animal models, summing up data about safety issues as well as possible target to treat in various diseases, the first feasibility trials in humans were established. Up-to-date, safety issues have been cleared for low-dose carbon monoxide inhalation (up to 500 ppm), while there is no clinical data regarding the injection or intake of any kind of CO-RM so far. Current models of human research include sepsis, acute lung injury, and acute respiratory distress syndrome as well as acute kidney injury. Carbon monoxide is a most promising candidate in terms of a therapeutic agent to improve outbalanced organ conditions. In this paper, we summarized the current understanding of carbon monoxide’s biology and its possible organ targets to treating the critically ill patients in tomorrow’s ICU.
A model of opinion and propagation structure polarization in social media
Authors: Prasetya Hafizh A. , Murata Tsuyoshi
Published: January 2020

The issue of polarization in online social media has been gaining attention in recent years amid the changing political landscapes of many parts of the world. Several studies empirically observed the existence of echo chambers in online social media, stimulating a slew of works that tries to model the phenomenon via opinion modeling. Here, we propose a model of opinion dynamics centered around the notion that opinion changes are invoked by news exposure. Our model comes with parameters for opinions and connection strength which are updated through news propagation. We simulate the propagation of multiple news under the model in synthetic networks and observe the evolution of the model’s parameters and the propagation structure induced. Unlike previous models, our model successfully exhibited not only polarization of opinion, but also segregated propagation structure. By analyzing the results of our simulations, we found that the formation probability of echo chambers is primarily connected to the news polarization. However, it is also affected by intolerance to dissimilar opinions and how quickly individuals update their opinions. Through simulations on Twitter networks, we found that the behavior of the model is reproducible across different network structure and sizes.
Analysis of river bed variation using SSARR and RMA-2 models
Authors: Hwang Ju Ha , Maeng Seung Jin , Kim Hyung San , Lee Seung Wook
Published: January 2020

Future changes in river bed were predicted under the assumption that flow velocity of past and changes in flow rate at upstream river due to construction of large-scale artificial structures downstream occur in the future. Therefore, the long-term runoff volume from the downstream part of Hosan Stream was estimated using the SSARR (Stream Synthesis and Reservoir Regulation Model). Changes in the river bed were simulated using RMA-2 and SED-2D, which are hydraulic models. As a result, it was found that the river bed variation is significantly affected by the inclusion of sediment in flood flow at upstream. A comprehensive evaluation of above results revealed that the river width has significantly affected flow rate, and the inclusion of sediment in flood flow from the upstream has a huge effect on changes in the riverbed. In this regard, there is a need to devise measures to mitigate future flood damage to artificial structures by reflecting sedimentation trends downstream before the construction of large-scale artificial structures at downstream of river.