bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of bariatric surgery in a Colombian population
Authors: León Claudia Y. Obando , Regino William Otero , FERNANDEZ HERNANDO MARULANDA , Ballén Hernán , Otero Elder
Published: September 2020

Background

Obesity (OB) is defined as having a body mass index (BMI) of ≥ 30 kg/m2. It has a high risk of mortality due to its association with comorbidities. Bariatric surgery (BS) is indicated for a BMI of 40 kg/m2 or of 35 kg/m2 if concurrent with a metabolic disorder.
Methods

A retrospective observational study of patients subjected to BS, such as Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric band (AGB). A survey was applied to determine the BMI and patterns of comorbidities before and after BS.
Results

The study included 30 patients who underwent 25 RYGB, 4 SG and 1 AGB procedures. A total of 17 patients were evaluated at the one-year follow-up and all showed improvement in comorbidities and weight loss, with a mean excess BMI loss (%EBMIL) of 89.5% At the two-year follow-up, 3 patients reported a %EBMIL of 75%. At the three-year follow-up, 10 patients had a %EBMIL of 70.8%%, but 70% (7/10) still had a BMI > 30 kg/m2. Type 2 diabetes mellitus resolved in all (12/12) and the doses of antihypertensive drugs were reduced in 86.4% of hypertensive patients (11/13). Half of the patients followed a diet.
Conclusion

In our service, BS was effective one year after the procedure. After three years, BMI > 30 kg/m2 persisted in 70% of patients All diabetics were cured. The doses of antihypertensives were lowered in 86.4% of hypertensive patients. Ultrasound scan detected no fatty liver diseases at the one-year follow-up of 85.7% of patients.
Application of Gene Expression Programming, Artificial Neural Network and Multilinear Regression in Predicting Hydrochar Physicochemical Properties
Authors: Abdulsalam Jibril , Lawal Abiodun Ismail , Setsepu Ramadimetja Lizah , Onifade Moshood , Bada Samson
Published: September 2020

Globally, the provision of energy is becoming an absolute necessity. Biomass resources are abundant and have been described as a potential alternative source of energy. However, it is important to assess the fuel characteristics of the various available biomass sources. Soft computing techniques are presented in this study to predict the mass yield (MY), energy yield (EY), and higher heating value (HHV) of hydrothermally carbonized biomass by using Gene Expression Programming (GEP), multiple-input single output-artificial neural network (MISO-ANN), and Multilinear regression (MLR). The three techniques were compared using statistical performance metrics. The coefficient of determination (R2), mean absolute error (MAE), and mean bias error (MBE) were used to evaluate the performance of the models. The MISO-ANN with 5-10-10-1 and 5-15-15-1 network architectures provided the most satisfactory performance of the three proposed models (R2 = 0.976, 0.955, 0.996; MAE = 2.24, 2.11, 0.93; MBE = 0.16, 0.37, 0.12) for MY, EY and HHV respectively. The GEP technique’s ability to predict hydrochar properties based on the input parameters was found to be satisfactory, while MLR provided an unsatisfactory predictive model. Sensitivity analysis was conducted, and the analysis revealed that volatile matter (VM) and temperature (Temp) have more influence on the MY, EY, and HHV.
The Role of S100A4 for Bone Metastasis in Prostate Cancer Cells
Authors: Kim Bongjun , Kim Haemin , Jung Suhan , Kwon Jun-Oh , Song Min-Kyong , Kim Min-Kyung , Kim Hyung Joon , Kim Hong-Hee
Published: September 2020

Background: Prostate cancers frequently metastasize to bone, where the best microenvironment for distant colonization is provided. Since osteotropic metastasis of prostate cancer is a critical determinant of patients’ survival, searches for preventive measures are ongoing in the field. Therefore, it is important to dissect the mechanisms of each step of bone metastasis, including the epithelial-mesenchymal transition (EMT) and cross-talk between metastatic niches and cancer cells.Methods: In this study, we established a highly bone-metastatic subline of human prostate cancer cells by selecting bone-homing population of PC3 cells after cardiac injection of eight-week-old male BALB/c-nude mice. Then we assessed the proliferation, EMT, and migration properties of the subline (mtPC3) cells in comparison with the parental PC3 cells. To investigate the role of S100A4, we performed gene knock-down by lentiviral transduction, or treated cells with recombinant S100A4 protein or a S100A4-neutralizing antibody. The effect of cancer cells on osteoclastogenesis was evaluated after treatment of pre-osteoclasts with conditioned medium (CM) from cancer cells.Results: The mtPC3 cells secreted a markedly high level of S100A4 protein and showed elevated cell proliferation and mesenchymal properties. The increased proliferation and EMT of mtPC3 cells was inhibited by S100A4 knock-down, but was not affected by exogenous S100A4. Furthermore, S100A4 released from mtPC3 cells stimulated osteoclast development via the cell surface receptor RAGE. Down-regulation or neutralization of S100A4 in the CM of mtPC3 cells attenuated cancer-induced osteoclastogenesis. Conclusion: Altogether, our results suggest that intracellular S100A4 promotes cell proliferation and EMT in tumor cells, and that secreted S100A4 activates osteoclastogenesis, contributing to osteolytic bone metastasis. Thus, S100A4 upregulation in cancer cells highly metastatic to bone might be a key element in regulating bone metastasis.
Network dynamics of drought-induced tipping cascades in the Amazon rainforest
Authors: Wunderling Nico , Staal Arie , Sakschewski Boris , Hirota Marina , Tuinenburg Obbe , Donges Jonathan , Barbosa Henrique , Winkelmann Ricarda
Published: September 2020

Tipping elements are nonlinear subsystems of the Earth system that can potentially abruptly and irreversibly shift if environmental change occurs. Among these tipping elements is the Amazon rainforest, which is threatened by anthropogenic activities and increasingly frequent droughts. Here, we assess how extreme deviations from climatological rainfall regimes may cause local forest-savanna transitions that cascade through the coupled forest-climate system. We develop a dynamical network model to uncover the role of atmospheric moisture recycling in such tipping cascades. We account for the heterogeneity in critical thresholds of the forest caused by adaptation to local climatic conditions. Our results reveal that, despite this adaptation, increased dry-season intensity may trigger tipping events particularly in the southeastern Amazon. Moisture recycling is responsible for one-fourth of the tipping events. If the rate of climate change exceeds the adaptive capacity of some parts of the forest, secondary effects through moisture recycling may exceed this capacity in other regions, increasing the overall risk of tipping across the Amazon rainforest.
Effects of Body Weight on the Safety of High-dose Donepezil in Alzheimer’s Disease: Post-hoc Analysis of a Multicenter, Randomized, Open-label, Parallel Design, Three-arm Clinical Trial
Authors: Hong Yun Jeong , Han Hyun Jeong , Youn YoungChul , Park Kyung Won , Yang Dong Won , Kim SangYun , Kim Hwa Jung , Kim Hyung-Ji , Kwon Miseon , Lee Jae-Hong
Published: September 2020

Background: Donepezil 23mg is considered for Alzheimer’s disease (AD) to optimize cognitive benefits; however, this increases adverse events (AEs), which can negatively influence drug adherence. We investigated whether baseline body weight (BW) differs based on the presence of AEs, and which factors were relevant to the safety of high-dose donepezil. Methods: This study was a post-hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with donepezil 10mg/day and the daily dose was escalated to 23mg with/without dose titration. Dose titration indicates 15mg/day of donepezil before the escalation or 10mg and 23mg/day on alternate days before the escalation during the first 4 weeks. The patients were divided into two groups according to the occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs.Results: Among 160 safety set population, baseline BWs were different between the AESI (+) (n=67) and AESI (-) (n=93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (p=0.020), and this relationship was more prominent in the no-dose titration group (p=0.009) and disappeared in the dose titration groups (p>0.05).Conclusions: BW was the most important factor which correlated with cholinergic AEs. Hence, stepwise dose-titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and AEs occurrence. (‘Clinicaltrials.gov’ number NCT02550665 registered on Sep. 15, 2015)
Proximal Junctional Kyphosis in Lenke 5 AIS Patients: The Important Factor of Pelvic Incidence
Authors: Zhou Quan , Hu Bowen , Yang Xi , Song Yueming , Liu Limin , Wang Linnan , Wang Lei , Zhou Chunguang , Zhou Zhongjie , Xiu Peng , Wang Liang
Published: September 2020

BackgroundThe purpose of the study was to investigate whether pelvic incidence (PI) will affect the occurrence of PJK in Lenke 5 AIS patients after correction surgery and try to explore a better surgical scheme based on PI.MethodsLenke 5C AIS patients that underwent correction surgery for thoracolumbar/lumbar (TL/L) curves with a minimum of a 2-year follow-up were identified. Demographic and radiographic data were collected preoperatively, postoperatively, and at the final follow-up. The comparison between the PJK and the Non-PJK group was conducted and the subgroup analysis was performed based on the preoperative value of PI to investigate the potential mechanism of PJK. ResultsThe mean preoperative Cobb angle of the TL/L curve was 53.4°±8.6. At the final follow-up, the mean TL/L Cobb angle was drastically decreased to 7.3°±6.8 (P <0.001). The incidence of PJK was 21.9% (7/32) in the low PI group (PI<45°) and 15.8% (6/38) in the high PI group (PI≥45°), and there was no statistical difference between the two groups (2=0.425, P > 0.05). The UIV of the PJK subgroup was much closer to the cranial level than the Non-PJK subgroup for the high PI group (PJK vs. Non-PJK: 6.0±1.3 vs. 8.6±1.6, P = 0.003). There was no significant difference in the selection of LIV between the two groups.ConclusionsThe incidence of PJK in Lenke 5 AIS was 18.6%. Our results found no difference in the incidence of PJK according to PI, but the mechanisms of PJK may be different for different PI values. The design of surgical plans for Lenke 5 AIS patients should take individual PI into account to decrease the incidence of PJK.
Treatment outcome following a single-visit coronal indirect restoration by a CAD/CAM technique in endodontically treated teeth with coronal contamination: A pilot retrospective study
Authors: Lin Xinwei , Chi Danlu , Tong Zhongchun
Published: September 2020

Background

It is not uncommon that coronal contamination might take place in some clinical cases of ETT following improper treatment choices. This clinical investigation evaluated the outcome of endodontically treated teeth (ETT) with adequate root canal treatment and less than 12 months of coronal contamination by only a single-visit coronal indirect restoration.
Methods

Twenty-five patients with less than 12 months of coronal contamination following adequate root canal treatment were selected in the period from June 2016 to June 2018, and a single-visit coronal coverage restoration was performed by a chairside computer-aided design/computer-assisted manufactured (CAD/CAM) technique. The clinical outcome was evaluated by radiographical and clinical examination at 1 ~ 3 years recall.
Results

Twenty-three patients paid a return visit at 1 ~ 3 years recall. All teeth showed no clinical symptoms and no sensitivity to percussion through single-visit coronal coverage restoration, and the radiographic examination showed no change in comparison to the preoperative perirapical X-ray. Three typical clinical scenarios are presented in detail.
Conclusions

Coronal contamination may not be a unique indicator of endodontic retreatment, and clinicians should evaluate the quality of pre-existing endodontic treatment by radiographical and clinical conditions to determine whether retreatment is necessary.
A Real-time Approach for Dynamic Scheduling Pet Activities in a Hospital
Authors: CHIOU SHIN-YAN , Dong Ya-Xin , Lin Kun-Ju
Published: September 2020

Background: At present, medical personnel use manual scheduling methods to calculate usage times of PET devices, hospital beds, operating rooms, and other treatment spaces. However, as patient treatment and recovery times are unequal and uncertain, arriving times of the scheduled/temporary patients are unexpected, examination items, beds requirements, and drugs waiting times are different, and scan-again requirements are unexpected. Manual scheduling arrangements are easy to make mistakes and put pressure on employees. With changing scheduling arrangements, it is difficult to announce the estimated time to patients and their families in real time. As a result, family members keep asking medical staff about various situations and waiting time. This makes the process unstable and exhausts the medical staff. Although previous researches proposed algorithms for specific inspections to solve the equipment resource allocation problems and calculate outpatient visit time for outpatient clinics, there is no research on improving the PET process. This paper proposes a real-time automatic scheduling and control system for PET patients with Bluetooth Beacon positioning. Results: This system can automatically schedule, estimate, and instantly update the start and end time of various tasks of PET patients during examinations, and automatically allocate beds and real-time announce schedule information, allowing the schedule being automated, instant and almost optimized. Moreover, this system promptly reminds medical staffs in each area. This can greatly reduce the work of medical staff, avoid human error, improve the safety of drugs, and provide medical staff, patients and family members to view the inspection progress and estimated waiting time in real time, reducing the number of patients and family members to query medical staff. We implemented this system in an application for the Android system to prove the feasibility of the system. We also collected time data of 200 actual patients for 2 weeks in the Department of Nuclear Medicine of Chang Gung Memorial Hospital, Linkou, and put these data into the implementation program for simulation and comparison. It was found that the average time difference between manual and automatic scheduling was 7.32 minutes, and it could reduce the average examination time of 82% of patients by 6.14 minutes, proving the system's correctness and efficiency. To our knowledge, this paper is the first to propose a real-time automatic scheduling and control system for PET patients.
A hybrid additive manufacturing platform to create bulk and surface composition gradients on scaffolds for tissue regeneration
Authors: Sinha Ravi , Cámara-Torres Maria , Scopece Paolo , Falzacappa Emanuele Verga , Patelli Alessandro , Moroni Lorenzo , Mota Carlos
Published: September 2020

Scaffolds with gradients of physico-chemical properties and controlled 3D architectures are crucial for engineering complex tissues. These can be produced using multi-material additive manufacturing (AM) techniques. However, they typically only achieve discrete gradients using separate printheads to vary compositions. Achieving continuous composition gradients, to better mimic tissues, requires material dosing and mixing controls. No such AM solution exists for most biomaterials. Existing AM techniques also cannot selectively modify scaffold surfaces to locally stimulate cell adhesion. A hybrid AM solution to cover these needs is reported here. A novel dosing- and mixing-enabled, dual-material printhead and an atmospheric pressure plasma jet to selectively activate/coat scaffold filaments during manufacturing were combined on one platform. Continuous composition gradients in both 2D hydrogels and 3D thermoplastic scaffolds were fabricated. An improvement in mechanical properties of continuous gradients compared to discrete gradients in the 3D scaffolds, and the ability to selectively enhance cell adhesion were demonstrated.
The Reciprocal Effects of Physical Activity and Happiness in Adolescents
Authors: Woudenberg Thabo Joshua van , Bevelander Kirsten E , Burk William J , Buijzen Moniek
Published: September 2020

BackgroundPositive associations exist between physical activity and happiness in adolescents. However, previous studies have mostly used self-reported measures and cross-sectional designs. There is a need for more insight into the directionality and duration of this association. The current study was the first to investigate whether an increase in physical activity leads to happiness and whether adolescents become more physically active when they are happier. These two effects were studied between (on a day-to-day basis) and within days (on an hour-to-hour basis).MethodsThe study used data from the MyMovez project in which 1484 adolescents between the ages of 8 and 17 years wore an accelerometer on their wrist and answered experience sampling questions on happiness at random moments during the day for several weeks in 2016–2018.ResultsThe preregistered analyses demonstrated an association between physical activity and happiness. More specifically, the number of steps per day predicted the experienced happiness on that day. In addition, a short-term reciprocal effect of physical activity and happiness was observed. Happiness was predicted by the number of steps accumulated in the previous hour and it also predicted the number of steps accumulated in the subsequent hour. However, convincing evidence was found that these effects did not occur in the long-term between days. The number of steps on the previous day did not predict happiness, nor did happiness predict the number of steps of the subsequent day.ConclusionsThis study confirms an association between physical activity and happiness in adolescents and shows that in the short-term, physical activity promotes happiness and vice versa. Therefore, we conclude that physical activity is not only important for the physical health of youth, but also plays an important role in their mental well-being. In addition, this knowledge can be used to further understand the importance of physical activity in adolescents’ health and help in promoting a healthy lifestyle among youth.RegistrationThe data used are stored at the Data Archiving and Networked Services (https://doi.org/10.17026/dans-zz9-gn44). Hypotheses, study design, sample, data collection procedure, measured variables, and plan of analysis were preregistered on the Open Science Framework (OSF, https://osf.io/64gw5/?view_only=0c6894d63eeb4cb5aa01d91d87085c56 [blinded for peer review]).
Impact Prognostic of Delayed Reperfusion Time in Patients With Stemi of ≤24 Hours Treated in the Emergency Department of a General Hospital
Authors: Socias Lorenzo , Frontera Guillem , Rubert Catalina , Torres Joan , Ripoll Tomas , Pascual Marcos , Carrillo Andres , Peral Vicente , Fiol Miquel
Published: September 2020

Background. The patients who attend a hospital without a hemodynamic laboratory may have differences in health outcomes, treatment, reperfusion times, the rate of cardiovascular complications, hospital stay, mortality or costs may be affected. The study aimed to analyze the prognostic of patients with STEMI treated in the Emergency Department (ED) and the impact prognostic of the delayed reperfusion time in a Hospital General without hemodynamic laboratory. Methods. After ethics review board approval, this retrospective observational cohort study of patients included acute coronary syndrome with ST elevation of ≤ 24 h in the Illes Balears infarction code registry (CI-IB) between May 2008 and December 2018. The information recorded were age, sex, cardiovascular risk factors, site of AMI, time delays, reperfusion therapy with fibrinolysis and primary angioplasty (PA). Cardiovascular Event (CE) was defined the combined variable: Killip class progression, malignant arrhythmias, Re-infarction, cerebrovascular disease and mortality. Results.605 patients were analyzed. The reperfusion treatment was 83,1% (80,8% with PA). 19% presented some CE. Hospital and monthly mortality was 6.8% and 7.8% respectively. The main differences between patients with and without CE were: age (66 vs 59 years); Chronic obstructive pulmonary disease (COPD); previous infarction; anterior location; Door-To-Needle Time and FPC-PA time. The risk factors of CE were: age, COPD, anterior location, fibrinolysis and patients without reperfusion treatment. In the group with PA, the risk of mortality was higher in COPD (p=0.012), Symptom start –FPC time with (p = 0,084) and FPC-PA time > 90 minutes (p= 0.107). FCM-AP> 90 minutes had a higher mortality (10 vs 4.4%;HR 1,79; IC 95% 1,15-2,78; log-rank:p=0,013)Conclussions. In our cohort, most patients received reperfusion treatment and were performed within the recommended time. In ED, the pacients with a FCM-PA time longer than recommended in the guidelines and COPD had higher CE y mortality.
A Trans Fatty Acid Substitute Aggravates Nonalcoholic Steatohepatitis Induced in Mice by Feeding a Choline-Deficient, Methionine-Lowered, L-Amino Acid-Defined, High-Fat Diet
Authors: Suzuki-Kemuriyama Noriko , Abe Akari , Uno Kinuko , Ogawa Shuji , Watanabe Atsushi , Sano Ryuhei , Yuki Megumi , Miyajima Katsuhiro , Nakae Dai
Published: September 2020

Background: Nonalcoholic steatohepatitis (NASH) is a form of liver disease characterized by steatosis, necroinflammation, and fibrosis, resulting in cirrhosis and cancer. Trans fatty acid (TFA) is hazardous for human health and a risk factor of NASH; thus, efforts have focused on reducing its intake. However, the health benefits of reducing dietary TFA are not fully elucidated. We investigated effects of TFA and its substitute on NASH induced in mice by feeding a choline-deficient, methionine-lowered, L-amino acid-defined, high-fat diet (CDAA-HF). Methods: Mice were fed CDAA-HF containing shortening with TFA (CDAA-HF-T(+)), CDAA-HF containing shortening with a TFA substitute (CDAA-HF-T(−)), or a control chow for 13/26 weeks. Results: CDAA-HF-T(+) contained TFA, whereas CDAA-HF-T(−) contained no TFA and much saturated fatty acids. CDAA-HF-T(+) and CDAA-HF-T(−) induced NASH in mice, evidenced by elevated serum transaminase activity and liver changes, including steatosis, inflammation, and fibrosis. CDAA-HF-T(−) induced more hepatocellular apoptosis and proliferative (preneoplastic and non-neoplastic) nodular lesions than CDAA-HF-T(+). Conclusions: Thus, replacement of dietary TFA with its substitute does not prevent but aggravates nutritionally induced NASH in mice, at least under the present conditions. Attention should be paid regarding future TFA substitute use in humans, and a fatty acid balance is likely more important than the particular types of fatty acids.
Vaginal Progesterone for Prevention of Preterm Birth in Asymptomatic High-Risk Women with a Normal Cervical Length: A Systematic Review and Meta-Analysis Protocol
Authors: Williams Kimberley Paige , McAuliffe Liam , Diacci Rosanna , Aubin Anne-Marie , Issah Ashad , Wang Carol , Phung Jason , Pennell Craig Edward
Published: September 2020

Background: Preterm birth (PTB) is estimated to affect 14.9 million babies globally every year. Global rates of PTB continue to increase from 9.8% to 10.6% over a 15-year period from 2000 to 2014. Vaginal progesterone is commonly used by clinicians as a prevention strategy, with recent evidence affirming the benefit of vaginal (micronized) progesterone to prevent PTB in women with a shortened cervix (<25mm). Given the low incidence of a short cervix at mid-gestation in high-risk populations further evidence is required. The objective of this review is to determine if vaginal progesterone reduces spontaneous preterm birth (sPTB) before 37 weeks in asymptomatic high-risk women with a singleton pregnancy with a normal mid-gestation cervical length. Methods: Studies will be sourced from MEDLINE and Embase databases with the search terms “progesterone” and “preterm birth”. Studies will be screened and included if they assess vaginal progesterone compared to placebo in women with a normal cervical length. The primary outcome will be sPTB <37 weeks, with secondary outcomes of sPTB <34 weeks. Two independent reviewers will conduct study screening at abstract and full text level, data extraction and risk of bias assessment with disagreements resolved by an experienced researcher. The Mantel-Haenszel statistical method and random effects analysis model will be used to produce treatment effect odds ratios and corresponding 95% confidence intervals.Discussion: This review will assess the current body of evidence and provide clarity regarding the potential benefits and best practice of use of vaginal progesterone in asymptomatic women with high risk singleton pregnancies and normal cervical length. Trial registration: This study has been registered on PROSPERO with the registration number CRD42020152051
Long-Term Outcomes of Corneal Collagen Cross-Linking: Results of 6-Years Follow-Up
Authors: Csorba Anita , Kiss Huba , Kránitz Kinga , Nagy Zoltán Zsolt
Published: September 2020

Background: Our aim was to evaluate the long-term effects of conventional epithelium-off corneal cross-linking performed on patients with progressive keratoconus. Methods: A retrospective analysis was performed on 34 eyes of 34 patients with progressive keratoconus underwent conventional cross-linking using Pentacam HR Scheimpflug camera. Visual acuity, spherical equivalent, keratometry, pachymetry and corneal topographic indices were analysed preoperatively and at 1, 3, and 6 years after the surgery. Results: Statistically significant decrease was detected at 1 year in spherical equivalent (p = 0.022), with no significant changes afterward (p =0.616). Uncorrected and best corrected distance visual acuity improved significantly in the first postoperative year (p =0.017 and p= 0.003, respectively), and remained stable with no significant changes at further visits (p = 0.203 and p = 0.336, respectively). Significant decrease of central corneal thickness and thinnest corneal thickness was observed at 1 year (both p <0.001), with additional thinning of thinnest corneal pachymetry up to 3 years (p = 0.01). Maximum keratometry and mean keratometry showed significant, continuous improvement between all consecutive visits over the whole follow-up period (all p-values <0.05). Significant improvement was found in the following 5 topographic indices at 1 year: ISV (p = 0.001), IVA (p = 0.028), KI (p = 0.002), CKI (p <0.001 and Rmin (p <0.001), with further improvement up to 3 years in ISV (p = 0.007), in CKI (p = 0.019) and in Rmin (p = 0.015). Rmin showed more improvement up to the end of follow-up (p <0.001).Conclusions: Conventional epithelium-off corneal cross-linking is effective in halting the progression of keratoconus and in regularization of the anterior corneal surface over a long-term follow-up period up to 6 years.
Bone Marrow Mesenchymal Stem Cells Derived miRNA-130b Enhances Epithelial Sodium Channel by Targeting PTEN
Authors: Zhang Honglei , Hong Yapeng , Liu Yanhong , Zhou Zhiyu , Ding Yan , Nie Hongguang
Published: September 2020

Aims: Acute lung injury (ALI) is a clinical syndrome with high morbidity and mortality, and severe pulmonary edema is one of the characteristics of ALI. Epithelial sodium channel (ENaC) located on the apical side of alveolar type 2 epithelial (AT2) cells is the primary rate limiting segments in alveolar fluid clearance. Many preclinical studies have revealed that mesenchymal stem cells (MSCs) based therapy has great therapeutic potential for ALI, while the role of ENaC in this process is rarely known. Methods: We studied the effects of bone marrow-derived MSCs (BMSCs) on the protein/mRNA expression and activity of ENaC in primary mouse AT2 and H441 cells by co-culture with them, respectively. Moreover, the changes of miRNA-130b in AT2 cells were detected by qRT-PCR, and we studied the involvement of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in miRNA-130b regulated ENaC. Results: Our results demonstrated that BMSCs could increase the expression of miRNA-130b, which showed adverse effects on the protein expression of α/γ-ENaC and PTEN in AT2 cells. SiRNA-mediated downregulation of PTEN could increase the protein expression of α/γ-ENaC in AT2 cells, supporting PTEN as a negative regulator of ENaC. Conclusion: In summary, miRNA-130b in BMSCs can enhance ENaC at least partially by targeting PTEN, which may provide a promising new direction for therapeutic strategy in ALI.
FAP Beige Adipogenesis in Volumetric Muscle Loss
Authors: Wang Zili , Lee Carlin S. , He Jinshen , Jiang Kunqi , Liu Mengyao , Kim Hubert T. , Feeley Brian T. , Liu Xuhui
Published: September 2020

Background Volumetric muscle loss (VML) often leads to chronic muscle weakness, impaired limb function, and even permanent disability. Recent studies suggest muscle residential fibro/adipogenic progenitors (FAPs) can adopt novel beige fat differentiation promoting muscle regeneration. The goal of this study is to define the role of FAP beige adipogenesis in muscle regeneration after VML in a mouse model.Methods Three months old male C57BL/6J mice, PDGFRα-GFP reporter mice, UCP-1 reporter mice, PDGFRα-CREERT/DTA inducible FAP depletion mice and NSG immune-deficient mice were used in this study. Volumetric muscle loss (VML) was created on tibialis anterior (TA) muscle with a punch. To induce FAP beige adipogenesis, Amibegron, a beta 3 adrenergic receptor (B3AR) agonist was administered to mice with I.P. injection. In a separate group, murine and human beige adipogenic FAPs was transplanted to mouse muscle after VML. Limb function was measured with gait analysis at 2 and 6 weeks after VML. Muscle histology and FAP gene expression analysis was also conducted at 2 and 6 weeks after VML.Results After VML, we observed robust proliferation of FAPs in PDGFRα-GFP reporter mice. PDGFRα-CREERT/DTA mice inducible FAP depletion mice showed reduced muscle regeneration after FAPs are depleted, suggesting a positive role of FAP in muscle regeneration after VML. Both Amibegron treatment and beige FAP transplantation significantly improved muscle regeneration and limb function after VML.Conclusion Stimulating FAP beige adipogenesis with B3AR agonists or transplantation of beige adipogenic FAPs could serve as new strategies in treating VML.
Assessing Exposure to War-related Traumatic Events in Older Vietnamese War Survivors
Authors: Young Yvette , Korinek Kim , Zimmer Zachary , Tran Toan Khanh
Published: September 2020

Background: Though studies measuring war-related stressors and resultant trauma among U.S. military veterans are abundant, few studies address how wartime stressors affect military veterans native to warzones. Even fewer assess the stress exposure and resulting trauma experienced by civilians. This study aimed to develop and evaluate a measure of wartime stress exposure relevant for civilians and military veterans who survived the American War in Vietnam.Methods: The study analyzed data from a novel source, the Vietnam Health and Aging Study, which surveyed older men and women residing in central and northern Vietnam. We used a combination of exploratory and confirmatory factor analysis with posthoc tests of reliability and validity to derive measures for assessing exposure to war-related traumatic events.Results: We found that a mix of exposure to death, combat, inhospitable living conditions, and forced displacement comprises the traumatic events that potentially contribute to posttraumatic stress disorder and other mental health problems. However, the particular mix of stressful experiences constituting war trauma differs for civilians, veterans of the formal military, and former members of paramilitary organizations. Conclusions: These findings suggest the need for distinct, but parallel approaches to measuring war-related stressors for populations of veterans and civilians exposed to war in their home countries, and the need for greater public attention to the potential lingering trauma of noncombatants.
DA-EPOCH-R is more effective and less toxic than modified CODOX-M/IVAC-R for treating Chinese HIV-infected patients with Burkitt lymphoma: an uncontrolled retrospective clinical trial
Authors: Ding Xiaoyan , Sun Wei , Shen Yanjun , Guo Xiaodi , Teng Ying , Liu Xiaomin , Li Wendong , Chen Jinglong , Li Wei
Published: September 2020

BACKGROUND Burkitt lymphoma (BL), commonly associated with human immuno-deficiency virus (HIV) in China, is an aggressive B-cell lymphoma with a poor prognosis. Current treatments are insufficient and have severe side effects in adult patients with immunodeficiency. METHODS We retrospectively studied HIV-positive patients with untreated BL from December 2011 to June 2019. We compared a low-intensity treatment regimen comprising infused etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (dose-adjusted EPOCH-R, study group) and a dose-intensive regimen comprising cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, high-dose cytarabine, and rituximab (CODOX-M/IVAC-R, control group). Differences in survival outcomes, toxicity, and survival-associated factors were analyzed.RESULTS Twenty-eight consecutive patients were enrolled with integrated clinical data, with 18 patients in the DA-EPOCH-R group and 10 in the modified CODOX-M/IVAC-R group. The median age of patients was 40 years (range: 21–60 years). The median baseline absolute CD4+ cell count was 243.5 cells/µL. All patients had high-risk diseases. Overall, grade 3–4 toxicity was observed at least once in 22 patients. The principal grade 3–4 toxic events, namely leukopenia (100% vs. 50%), febrile neutropenia (90% vs. 22.2%), and thrombocytopenia (80% vs. 16.7%), were significantly higher in the control group than in the study group. One patient in the control group died of septic shock induced by pneumonia. The median follow-up time was 19 months, and the median overall survival (OS) was significantly improved in the study group compared with that in the control group [18.0 months (95% confidence interval [CI], 14.0–22.0 months) vs. 7.9 months (95% CI, 4.8–11.0 months), respectively; P = 0.032]. Treatment with DA-R-EPOCH was a favorable prognostic factor for OS (HR: 0.19 [95% CI: 0.05–0.68]; P = 0.011).CONCLUSIONS DA-EPOCH-R may be an alternative to modified CODOX-M/IVAC-R, with better efficacy and lower toxicity, for treating Chinese patients with high-risk HIV-associated BL.
Ultrahigh ionic conductivity in optimally sintered Li10.35Ge1.35P1.65S12 superionic conductor
Authors: Wen Hao , Jiang Yue , Liu Xingang , Zhu Xiaohong , Zhang Chuhong
Published: September 2020

Lithium superionic conductor Li10+δGe1+δP2−δS12 has attracted tremendous interest for advanced all-solid-state lithium ion batteries due to extremely high ionic conductivity. However, the synthetic processes reported in literature are widely divergent, resulting in an order of magnitude difference in ionic conductivities of the same material, but as far as we know, the influence of synthetic conditions on ionic conductivity has not been studied yet. Herein, we systematically investigate the influence of sintering temperature on phase composition and ionic conductivity of the Li10+δGe1+δP2−δS12 compounds synthesized by conventional solid-state reaction for the first time. It is found that low and high sintering temperatures lead to a low crystallinity and the formation of impurity phases, respectively. As a result, the pure Li10.35Ge1.35P1.65S12, well crystallized in space group P42/nmc, is fabricated by optimization of the solid-state reaction temperature at 580 °C and its room temperature conductivity (19 mS cm− 1) is the highest among all existing Li10+δGe1+δP2−δS12 solid electrolytes. Meanwhile, the microstructure of Li10.35Ge1.35P1.65S12, being very dense and uniform, is demonstrated firstly by atomic force microscopy.
Serum Amyloid A levels and α2- and Gamma globulins on Serum Protein Electrophoresis in cats exposed to and infected with Leishmania infantum
Authors: Savioli Giulia , Archer Joy , Brianti Emanuele , Schnyder Manuela , Iatta Roberta , Otranto Domenico , Cantacessi Cinzia
Published: September 2020

Background: Although dogs are the main reservoir host of Leishmania infantum, recent investigations indicate a role for cats in its epidemiology. Feline leishmaniosis (FeL) remains poorly characterised, partly due to the lack of diagnostic tools. This study aimed to compare Serum Amyloid A (SAA) levels and serum protein electrophoresis (SPE) profiles (specifically, α2- and gamma globulins) in cats naturally exposed to or infected by L. infantum from southern Italy with those of healthy controls and of cats with neoplastic or inflammatory conditions from non-endemic areas.Methods: Serum or plasma samples from four cohorts of cats were analysed for SAA and by SPE, i.e G1: healthy controls from Leishmania-non-endemic regions of Switzerland, G2: cats pre-diagnosed with neoplastic or inflammatory conditions from the University of Cambridge’s sample archive, G3: L. infantum seropositive, qPCR-negative cats from southern Italy, G4: L. infantum seropositive and qPCR-positive cats from southern Italy. SAA data was assessed for normality using the Kolmogorov-Smirnoff and Shapiro-Wilk normality tests, then compared using a homogeneity of variance test for non-parametric data; the Kruskall-Wallis test, followed by Dunn’s multiple comparison test were used to compare SAA serum levels between groups. The Fisher’s Exact test was used to assess statistically significant differences in the numbers of animals displaying elevated gamma globulins and increased α2-globulins between groups.Results: Overall, 68 samples were analysed (G1 n=16, G2 n=20, G3 n=20, G4 n=12). Cats previously exposed to and/or infected with L. infantum, as well as cats suffering from neoplastic and inflammatory conditions showed significantly higher SAA levels (median values G1=0.00 (0.00-0.00) mg/L, G2=0.85 (0.00-49.55) mg/L, G3=0.00 (0.00-4.53) mg/L, G4= 0.00 (0.00-7.5) mg/L), and higher percentages of cats with increased α2-globulins (G1=20.0% ±10.3, G2=80.0% ±8.9, G3=70.0% ±10.2, G4=75.0% ±12.5) and gamma globulins (G1=0.0% ±0, G2=65.0% ±10.7, G3=50.0% ±11.2, G4=58.3% ±14.2) than healthy control cats. For all three markers, there was no significant difference between G2, G3 and G4.Conclusions: This study indicates that, whilst levels of gamma and α2-globulins and SAA are significantly elevated in cats infected by L. infantum, they cannot be used to differentiate between L. infantum infection or exposure and neoplastic or inflammatory conditions. Nevertheless, these indicators might assist monitoring of ongoing FeL if further studies indicate reduction during or following successful treatment.
WITHDRAWN: Examining Substance Use Services and Treatment Barriers and Needs among People with Lived Experience (PWLE) in Ontario, Canada.
Authors: Russell Cayley , Ali Farihah , Nafeh Frishta , LeBlanc Sean , Imtiaz Sameer , Elton-Marshall Tara , Rehm Jürgen
Published: September 2020

Introduction: Substance use is a complex issue, with rates of illicit and licit substances varying across Canada, and in Ontario, specifically. Services and treatment options for problematic substance use remain vital. Recent initiatives to increase the effectiveness of services have been implemented, however, a disconnect remains between the availability and accessibility of these programs and the real-world experiences and needs of people with lived experience (PWLE). There is a lack of knowledge regarding barriers to accessing services and service needs, yet PWLE are best suited to identify these factors. As such, this study critically examined these issues among a cohort of PWLE in Ontario, Canada. Methods: Semi-structured, one-on-one interviews with n=50 adult PWLE participants were conducted. Participants were recruited from substance use services across Ontario, based on ConnexOntario’s directory of all provincial addiction services, as well as by word-of-mouth. Questions focused on participants’ experiences and perspectives on substance use services. All data were transcribed and underwent an inductive thematic analysis based on key themes that emerged. Results: Beneficial services identified varied based on participant experiences and needs. A variety of barriers to service access were acknowledged, primarily related to system-level issues such as an overall lack of services, a lack of service capacity, and a severe lack of service coordination and gaps in service delivery. Recommendations revolved around the need for low-barrier, affordable, seamless services run by non-judgemental staff, including fellow PWLE. Conclusions: This study identified needs and barriers to substance use care among PWLE in Ontario, and highlighted important areas for policy change and program planning and implementation. Concrete recommendations include the development of a government-funded, low-barrier, comprehensive and integrated model of substance use services that includes PWLE as collaborators and program facilitators to ensure that services are as successful and meaningful as possible. Results from this study will work towards the improvement of substance use treatment and service provision across the province.
CircINSR regulates fetal bovine muscle and fat development
Authors: Shen Xuemei , Tang Jia , Ru Wenxiu , Zhang Xiaoyan , Huang Yongzhen , Lan Xianyong , Lei Chuzhao , Cao Hui , Chen Hong
Published: September 2020

Background: The level of muscle development directly affects the production efficiency of livestock, and the content of intramuscular fat (IMF) is an important factor affecting meat quality. Nevertheless, the molecular mechanism of embryonic circular RNA in muscle and IMF development remains largely unknown. Methods: In this study, we isolated myoblasts and intramuscular preadipocytes from fetal bovine skeletal muscle. Oil Red O and BODIPY staining were used to identify lipid droplets of preadipocytes, and anti-MyHC immunofluorescence was used to identify myotubes differentiated from myoblasts. Bioinformatics, dual fluorescence reporter system, and RNA immunoprecipitation were used to determine the interactions between circINSR and miR-15/16 family. Molecular and biochemical assays were used to confirm the role of circINSR in myoblasts and intramuscular preadipocytes. Results: We found that the isolated myoblasts and preadipocytes can differentiate normally. Besides, circINSR severed as a sponge of miR-15/16 family, which targeting CyclinD1 and Bcl-2. CircINSR overexpression significantly promoted myoblasts and preadipocytes proliferation, and inhibited cell apoptosis. In addition, circINSR inhibited preadipocytes adipogenesis by alleviating the inhibition of miR-15/16 on target genes FOXO1 and EPT1. Conclusions: Taken together, our study demonstrated circINSR as a regulator of embryonic muscle and IMF development.
Inverse molecular docking reveals a novel function of thymol: inhibition of fat deposition induced by high-dose glucose in Caenorhabditis elegans
Authors: Ban Fangfang , Hu Liangbin , Zhou Xiaohui , Zhao Yanyan , Mo Haizhen , Li Hongbo , Wei Zhou
Published: September 2020

Background As a natural product isolated from thyme oil in thyme, thymol (2-isopropyl-5-methylphenol) harbors antiviral, antioxidant, and other properties, and thus could be potentially used for the treatment of various diseases. However, the function of thymol has not been comprehensively studied.Methods Here, we applied an inverse molecular docking approach to identify unappreciated functions of thymol. Potential targets of thymol in humans were identiﬁed by the server of DRAR-CPI, and targets of interest were then assessed by GO and KEGG pathway analysis. Subsequently, homologous proteins of these targets in Caenorhabditis elegans were identified by Blast tool and their three-dimensional structures were achieved using Swiss-Model workspace. Interaction between thymol and the targeted proteins in worms was verified using AutoDock 4.0. To verify the activity of thymol on lipid deposition in vivo, the C. elegans model was established. The lipid content of nematodes induced by high-dose glucose was determined by Oil Red O and Nile Red staining, and gene expression related to fat accumulation was assessed by qRT-PCR. Results Analyses of the targets revealed that thymol could be potentially involved in the glycolysis/gluconeogenesis and fatty acid degradation pathways. Experiment results in vivo verified that 1 μg/mL and 5 μg/mL thymol treatment significantly reduced lipid deposition in glucose-induced nematodes. The result of qRT-PCR suggested that the decreased level of cpt-1, aco, fabp and tph-1 correlating with β-oxidation in nematodes exposed by 1mM glucose were upregulated after the exposure of thymol.Conclusions The results showed that thymol might lead to the acceleration of β-oxidation by upregulating cpt-1, aco, fabp and tph-1, causing the descent of lipid content in nematodes, which is potentially used for the treatment of chronic metabolic diseases associated with increased fatty acid deposition.
Canthin-6-One 9-O-Beta-Glucopyranoside: an inhibitor of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/ 3CLpro
Authors: Verma Devvret , Mitra Debasis , Kamboj Anshul , Mahakur Bhaswatimayee , Chaudhary Priya , Shrivastav Rakesh , Janmeda Pracheta , Pant Kumud , Mohapatra Pradeep K. Das
Published: September 2020

The rapid spread of SARS-CoV-2 has raised a severe global public health issue, where therapy is not identified with specific drugs or vaccines. The present investigation dealt with the inhibition of various proteins and receptors of virus using phytocompounds of three pertinent medicinal plants i.e. Eurycoma harmandiana, Sophora flavescens and Andrographis paniculata. Phytocompounds known to have antiviral properties were screened against the papain-like protease (PLpro) and main protease (Mpro) / 3-chymotrypsin-like Protease (3CLpro). Molecular docking with Canthin-6-One 9-O-Beta-Glucopyranoside showed the highest binding affinity and least binding energy with both the proteases viz. PLpro and Mpro/ 3CLpro. ADMET analysis of the compound suggested that it is having drug-like properties like high gastrointestinal (gi-) absorption, no blood-brain barrier permeability, and high lipophilicity.