bluuebunny/crossref_metadata_2025 huggingface dataset:
Modified R.E.N.A.L nephrometry score for predicting the outcome following partial nephrectomy
Authors: Salah Mohammed , ElSheemy Mohammed S. , Ghoneima Waleed , Abd El Hamid Mahmoud , Kassem Ayman , Ashmawy Ahmed Abdallah , Saad Ismail R. , Mosharafa Ashraf A. , Salem Hosni Khairy , Badawy Hesham , Salem Ahmed
Published: October 2020

Background

It was difficult to compare the outcome of partial nephrectomy among different studies due to the absence of standardized description of different renal masses. This problem led to the development of nephrometry scoring systems. R.E.N.A.L. is among the commonest nephrometry scoring systems; however, some studies failed to find any relation between R.E.N.A.L. with perioperative outcome. We evaluated our designed newly modified nephrometry score in prediction of outcome following partial nephrectomy and compared its predictability versus original R.E.N.A.L.

Methods

Fifty-one patients with cT1-2N0M0renal masses amenable for partial nephrectomy were included prospectively. Different perioperative outcome variables were compared according to complexity level in R.E.N.A.L. and the newly modified nephrometry score.

Results

Clinical staging was T1a (21.6%), T1b (49%), T2a (25.5%), T2b (3.9%). Median R.E.N.A.L. was 9 (4–12). Hilar position and intrarenal pelvis were detected in 19.6% and 68.6%. Low, moderate and high complexity masses were found in 21.6%, 39.2% and 39.2%. Complications and rate of conversion to radical nephrectomy were 17 (33.3%) and 4 (7.8%). The only significantly affected variable (p = 0.039) by R.E.N.A.L. was rate of secondary intervention, but it was higher in low than in high complexity level. In the newly modified nephrometry score, complications (p = 0.037) and rate of positive surgical margin (p = 0.049) were significantly higher with increased complexity level. Although other variables (pelvi-calyceal system entry, operative time, blood loss, hemoglobin loss, blood transfusion and conversion to radical nephrectomy) did not show statistically significant difference according to both scores, they were better associated with the complexity level in the newly modified nephrometry score with their remarkable increase in the high when compared to the low complexity level.

Conclusions

The newly modified nephrometry score was associated with better prediction of outcome of partial nephrectomy when compared to R.E.N.A.L.
Impact of simulated sunlight on the degradation of pendimethalin in surface water in a scale-up experiment in accordance to OECD TG 309
Authors: Hennecke Dieter , Hassink Jan , Klein Judith , Kruse Mike
Published: October 2020

Background

OECD TG 309 “Aerobic Mineralisation in Surface Water” (OECD Test Guideline 309 (2004)) is currently used in regulation for the assessment of the persistence of chemicals in surface water. The test is performed in a batch under defined conditions. Processes which might be relevant for the fate of a chemical in surface water like direct and indirect photolysis are not addressed. In order to study the impact of sunlight on the fate in surface water, pendimethalin, a herbicidal active substance with known sensitivity to aqueous photolysis, was used. This was tested in an experiment based on OECD 309, but scaled up to 900 L size with a 1.40 m water column and irradiated with special lamps in order to monitor the fate of the substance at different water depths, in comparison to dark controls.

Results

Pendimethalin degraded significantly under the applied test conditions. The test setups with exposure to simulated sunlight showed a significant faster degradation compared to the dark experiments. Application of 900 g sediment (1% of test system) to the test system further increased the degradation rate. In the simulated sunlight setups a faster degradation was observed in the upper water layer, hence, the concentration of the photolysis products were highest in the upper water layer, where the highest light intensity was measured. With decreasing light intensity in deeper water layers photolysis products were still detected at a water depth of 125 cm. Mineralisation up to 22% of the applied radioactivity was observed. In the dark controls neither significant amounts of photolysis products nor any mineralisation were detected. Among the different sampling depths no significant differences were observed. It was further observed that the dark controls became anaerobic at the end of the incubation time. This has been observed previously in standard laboratory tests according to OECD 309.

Conclusions

The study proves that for a substance sensitive to photolysis like pendimethalin, exposure to simulated sunlight leads to a significantly reduced degradation half-life (DegT50) in surface water compared to the dark control. In the standard test according to OECD guideline 309 the influence of photolytical degradation is not considered and thus the laboratory test can lead to the overestimation of the persistence of a chemical in surface water and consequently to a false-positive evaluation in the overall PBT assessment (ECHA Guidance on Information Requirements and Chemical Safety Assessment 2004), when only the results of the standard OECD 309 study are considered.
An embedded gene selection method using knockoffs optimizing neural network
Authors: Guo Juncheng , Jin Min , Chen Yuanyuan , Liu Jianxiao
Published: October 2020

Background

Gene selection refers to find a small subset of discriminant genes from the gene expression profiles. How to select genes that affect specific phenotypic traits effectively is an important research work in the field of biology. The neural network has better fitting ability when dealing with nonlinear data, and it can capture features automatically and flexibly. In this work, we propose an embedded gene selection method using neural network. The important genes can be obtained by calculating the weight coefficient after the training is completed. In order to solve the problem of black box of neural network and further make the training results interpretable in neural network, we use the idea of knockoffs to construct the knockoff feature genes of the original feature genes. This method not only make each feature gene to compete with each other, but also make each feature gene compete with its knockoff feature gene. This approach can help to select the key genes that affect the decision-making of neural networks.

Results

We use maize carotenoids, tocopherol methyltransferase, raffinose family oligosaccharides and human breast cancer dataset to do verification and analysis.

Conclusions

The experiment results demonstrate that the knockoffs optimizing neural network method has better detection effect than the other existing algorithms, and specially for processing the nonlinear gene expression and phenotype data.
Subcutaneous injection of IFN alpha-2b for COVID-19: an observational study
Authors: Wang Bo , Li Diandian , Liu Tao , Wang Haohua , Luo Fengming , Liu Yanbin
Published: October 2020

Background

The global pandemic of coronavirus disease 2019 (COVID-19) infection is ongoing and associated with high mortality. The aim of this study was to investigate the efficacy and safety of subcutaneous injection of interferon alpha-2b (IFN alpha-2b) combined with lopinavir/ritonavir (LPV/r) in the treatment of COVID-19 infection, compared with that of using LPV/r alone.

Methods

Patients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020 were included. The length of stay, the time to viral clearance and adverse reactions during hospitalization were compared between patients using oral LPV/r and combined therapy of LPV/r and subcutaneous injection of IFN alpha-2b.

Results

A total of 22 patients were treated with LPV/r alone and 19 with combined therapy with subcutaneous injection of IFN alpha-2b. The average length of hospitalization in the combination group was shorter than that of LPV/r group (16 ± 9.7 vs 23 ± 10.5 days; P = 0.028). Moreover, the days of hospitalization in early intervention group decreased from 25 ± 8.5 days to 10 ± 2.9 days compared with delayed intervention group (P = 0.001). Combined therapy with IFN alpha-2b also significantly reduced the duration of detectable virus in the upper respiratory tract. No patient in each group was transferred to intensive care unit (ICU) or died during the treatment. There was no significant difference in the adverse effect composition between two groups.

Conclusions

Subcutaneous injection of IFN alpha-2b combined with LPV/r shortened the length of hospitalization and accelerated viral clearance in COVID-19 patients, which deserves further investigation in clinical practice.
Plasma lipid levels and risk of primary open angle glaucoma: a genetic study using Mendelian randomization
Authors: Xu Mengqiao , Li Shengguo , Zhu Jundong , Luo Dawei , Song Weitao , Zhou Minwen
Published: October 2020

Background

The causal effects of plasma lipid concentrations and the risk of primary open angle glaucoma (POAG) are still unclear. Thus, the purpose of this study was to identify, applying a two-sample Mendelian randomization (MR) analysis, whether plasma lipid concentrations are causally associated with the risk of POAG.

Methods

Two-sample MR analysis of data from a genome-wide association study (GWAS) was performed to investigate the causal role of plasma lipid levels and POAG. A total of 185 independent single-nucleotide polymorphisms (SNPs) associated with plasma lipid levels were selected as instrumental variables (IVs). The SNPs were obtained from a meta-analysis of GWAS based on 188,577 European-ancestry individuals for MR analyses. Association with POAG for the SNPs was obtained from a GWAS conducted among the United Kingdom (UK) Biobank study participants with a total of 463,010 European-ancestry individuals. Four MR methods (inverse variance weighted [IVW], weighted mode, weighted median, and MR-Egger regression) were applied to obtain the overall causal estimate for multiple, instrumental SNPs.

Results

Using the IVW analysis method, no evidence was found to support a causal association between plasma LDL-C level and POAG risk (β = − 0.00026; 95% CI = -0.00062, 0.00011;P = 0.165) with no significant heterogeneity among SNPs. The overall causal estimate between plasma LDL-C level and POAG was consistent using the other three MR methods. Using the four MR methods, no evidence of an association between plasma HDL-C (β = 0.00023; 95% CI = -0.00015, 0.00061;P = 0.238; IVW method) or TG levels (β = − 0.00028; 95% CI = -0.00071, 0.00015;P = 0.206; IVW method) and POAG risk was found. Sensitivity analyses did not reveal any sign of directional pleiotropy.

Conclusions

The present study did not find any evidence for a causal association between plasma lipid levels and POAG risk. Further research is needed to elucidate the potential biological mechanisms to provide a reasonable interpretation for these results.
Correlates of fasting blood glucose among children living with hiv in a Nigerian tertiary hospital: a cross-sectional study
Authors: Ohuche Ijeoma Onyinye , Chikani Ugo Nnenna , Oyenusi Elizabeth Eberechi , Onu Justus Uchenna , Oduwole Abiola
Published: October 2020

Background

There is growing concern as regards the emergence of metabolic disorders among children living with the Human Immunodeficiency Virus (HIV) worldwide. However, there is paucity of data on the correlates of metabolic indices among HIV-positive children in Africa.

Methods

This study examined 84 HIV-positive children on HAART recruited from the paediatric infectious diseases clinic of the University of Nigeria Teaching Hospital for blood glucose levels using finger-prick testing with an Accu-check glucose meter and test strips. Clinical information was obtained via clinical history and medical records. Data was analyzed to examine the relationship between FBG and the classes of HAART, duration of illness and treatment using analysis of variance (ANOVA).

Results

FBG was significantly associated with the classes of HAART (x2=12.4, p = 0.017). In addition, there was a significant association between FBG and duration of illness [F(2, 81) = 6.0; P = 0.004], as well as FBG and duration on HAART [F(2, 81) = 7.9; P = 0.001]. However, duration on HAART and type of HAART were the significant predictors of FBG in this study accounting for 10.5% and 4.1% of the variance, respectively.

Conclusions

There is a greater risk of dysglycemia in paediatric patients with a longer cumulative exposure to HAART. Routine blood glucose checks among children on HAART, especially those who have received HAART for a longer duration of time may therefore be useful in their management.
The association between dietary glycemic and insulin indices with incidence of cardiovascular disease: Tehran lipid and glucose study
Authors: Teymoori Farshad , Farhadnejad Hossein , Mirmiran Parvin , Nazarzadeh Milad , Azizi Fereidoun
Published: October 2020

Background

The present study was conducted to investigate the association of dietary insulin index(II), insulin load(IL), glycemic index(GI), and glycemic load(GL) with the risk of cardiovascular disease(CVD).

Methods

This cohort study was conducted within the framework of the Tehran Lipid and Glucose Study on 2198 subjects, aged≥19 years old, who were followed-up for a median (IQR) 6.7 (6.1–7.1) years. Dietary GI, GL, II, and IL were calculated using a food frequency questionnaire at the baseline. Multivariate Cox proportional hazard regression models were used to estimate the risk of CVD across quartiles of dietary insulin and glycemic indices.

Results

Mean ± SD age of the subjects(44.9% men) was 38.3 ± 13.4 years. During a mean of 2406 ± 417 person-years of follow-up, 76(3.5%) new cases of the CVD were ascertained. The mean ± SD of II, IL, GI, and GL of participants were 51.7 ± 6.5, 235.8 ± 90.2, 61.9 ± 7.8, and 202.2 ± 78.1, respectively. After adjusting for the variables of age, sex, smoking, physical activity, daily energy intake, body mass index, diabetes, and hypertension, the hazard ratio (HR) of the highest quartile of dietary GL was 2.77(95%CI:1.00–7.69,P for trend:0.033) compared to the lowest one. Also, each one SD increase in the GL score was associated with a higher risk of CVD[(RR:1.46;CI:1.00–2.16),P-value = 0.047]. However, there was no significant association between the dietary GI, II, and IL and risk for CVD incidence.

Conclusions

Our results suggested that a high GL diet can increase the incidence of CVD, whereas high dietary II and IL were not associated with the risk of CVD among adults.
Small bowel volvulus (SBV) in Northcentral Ethiopia
Authors: Awedew Atalel Fentahun , Belay Woldemariam Beka , Amsalu Bedemariam Tadesse , Yalewu Dawit Zerihun
Published: October 2020

Background

Small bowel volvulus (SBV) is a benign gastrointestinal surgical condition in which there is a torsion of all or parts of a segment of small bowel on its mesenteric axis. It has been contributed significant burden of surgical emergency as cause of small bowel obstruction in developing countries. The main objective this study was to explore clinical and epidemiological profile of Small bowel volvulus in Northcentral Ethiopia.

Method

The study was conducted at Debre Tabor General Hospital, South Gondar in Northcentral Ethiopia. The medical records of patients with a discharge diagnosis of small bowel volvulus were reviewed. The patients were seen for a 4-year period from Jan1, 2016-Dec31, 2019. The study was hospital-based retrospective cross-sectional and data were collected with a standardized structure questioner tool. The collected data checked for any inconsistency, code, and enter SPSS version 23 for data processing and analysis. Descriptive analyses were represented as frequency, percent, mean ± standard deviation for normal distribution, and Median ± Interquartile range for skewed data. Cross tabulation analysis was done for risk factors contributed for mortality and morbidity of SBV.

Result

There were 148 patients with Small bowel volvulus as a cause of small bowel obstruction was admitted within 4 years. The annual occurrence rate was 35cases per year. It represented 59% of small bowel obstruction and 36.3% of bowel obstruction. The majority were males (N = 125, 84.5%) and females were (N = 23, 15.5%). The age ranged from 15 to 78 years. The mean age was 41.14 ± (SD = 15.4). The most common clinical presentation was abdominal pain 98% and vomiting 91.2%. The median time of hospital stay was 5 days (± IQR = 2). The mean duration of illness before hospital admission was 2 days (± SD = 1.4) and median was 1 day (± IQR = 2). The morbidity rate was 5.4% (N = 8) and the mortality rate was 3.4%(N = 5).

Conclusion

Annual occurrence of SBV was 37 cases per year. The prevalence of SBV was 59% of small bowel obstruction and 36.3% of bowel obstruction respectively.
Kojic acid repurposing as a pancreatic lipase inhibitor and the optimization of its production from a local Aspergillus oryzae soil isolate
Authors: El-Korany Sarah Mohamed , Helmy Omneya Mohamed , El-Halawany Ali Mahmoud , Ragab Yasser El-Mohammadi , Zedan Hamdallah Hafez
Published: October 2020

Background

Obesity and its related diseases are increasing worldwide. One of the best therapeutic strategies for obesity management is through the inhibition of pancreatic lipase (PL) enzyme. So far orlistat is the only FDA approved PL inhibitor, but with unpleasant side effects. New efficacious anti-obesity drugs are needed to achieve a successful reduction in the incidence and prevalence of obesity. Many microbial metabolites have PL inhibitory activity. Screening soil inhabitants for PL inhibitors could help in increasing the available anti-obesity drugs. We aimed to isolate and identify alternative PL inhibitors from soil flora.

Results

We screened the crude mycelial methanolic extracts of 39 soil samples for PL inhibitory activity by the quantitative lipase colorimetric assay, using the substratep-nitrophenyl palmitate and orlistat as positive control. AspsarO, a PL inhibitor producer, was isolated from an agricultural field soil in Giza, Egypt. It was identified asAspergillus oryzaeusing colony morphology, microscopical characteristics,18SrDNA sequencing, and molecular phylogeny. Increasing the PL inhibitor activity, in AspsarO cultures, from 25.9 ± 2% to 61.4 ± 1.8% was achieved by optimizing the fermentation process using a Placket–Burman design. The dried 100% methanolic fraction of the AspsarO culture had an IC50of 7.48 μg/ml compared to 3.72 μg/ml for orlistat. It decreased the percent weight gain, significantly reduced the food intake and serum triglycerides levels in high-fat diet-fed Sprague–Dawley rats. Kojic acid, the active metabolite, was identified using several biological guided chromatographic and1H and13C NMR techniques and had an IC50of 6.62 μg/ml. Docking pattern attributed this effect to the interaction of kojic acid with the key amino acids (Lys80, Trp252, and Asn84) in PL enzyme binding site.

Conclusion

Combining the results of the induced obesity animal model, in silico molecular docking and the lipase inhibitory assay, suggests that kojic acid can be a new therapeutic option for obesity management. Besides, it can lower serum triglycerides in obese patients.
Who are the ostomy patients and caregivers attending Portuguese community pharmacies? A cross-sectional study
Authors: Romão Mariana , Figueira Débora , Galante Heloísa , Guerreiro José , Romano Sónia
Published: October 2020

Background

In 2017, ostomy patients gained access to ostomy products in community pharmacies that are fully reimbursed by the Portuguese National Health Service. This impacted the daily lives of people with ostomy and opened a new market of products and services for pharmacies. However, little is known about the sociodemographic and clinical profile of ostomy patients. This study aims to characterize people with ostomy and their caregivers, evaluate access and satisfaction with the pharmacy and explore participants’ expectations regarding services and counselling.

Methods

This was an observational, cross-sectional, multicentre study involving pharmacy users who acquired ostomy products in Portuguese community pharmacies. Data were collected through a confidential self-report questionnaire between June and August 2019.

Results

Approximately 56% of the participants were ostomy patients, of whom 65.9% were men. The average age of participating ostomy patients was 65.5 years old (SD = 12.9), and near 80% were retired/pensioners. Caregivers were mostly women (81.7%). More than half of the caregivers were employed and acquired products for a direct family member. Three in every four surgical interventions were consequences of cancer. Intestinal ostomy was the most common intervention (78.3%). More than 93% were satisfied with the acquisition of ostomy products at the pharmacy. Approximately 48.2% of ostomy patients received care from a specialized nurse.

Conclusion

This study describes the profile of people with ostomy and their caregivers who attend community pharmacies in Portugal. Participants’ perceptions of the utility of different proposed services and pharmacist knowledge, as well as the low coverage of ostomy nursing care, highlight the opportunity for an extended role of pharmacists among this group.
Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties
Authors: Sharpe Lara , Sinclair Justin , Kramer Andrew , de Manincor Michael , Sarris Jerome
Published: October 2020

Background

Cannabis has been documented for use in alleviating anxiety. However, certain research has also shown that it can produce feelings of anxiety, panic, paranoia and psychosis. In humans, Δ9-tetrahydrocannabinol (THC) has been associated with an anxiogenic response, while anxiolytic activity has been attributed mainly to cannabidiol (CBD). In animal studies, the effects of THC are highly dose-dependent, and biphasic effects of cannabinoids on anxiety-related responses have been extensively documented. A more precise assessment is required of both the anxiolytic and anxiogenic potentials of phytocannabinoids, with an aim towards the development of the ‘holy grail’ in cannabis research, a medicinally-active formulation which may assist in the treatment of anxiety or mood disorders without eliciting any anxiogenic effects.

Objectives

To systematically review studies assessing cannabinoid interventions (e.g. THC or CBD or whole cannabis interventions) both in animals and humans, as well as recent epidemiological studies reporting on anxiolytic or anxiogenic effects from cannabis consumption.

Method

The articles selected for this review were identified up to January 2020 through searches in the electronic databases OVID MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, and PsycINFO.

Results

Acute doses of CBD were found to reduce anxiety both in animals and humans, without having an anxiogenic effect at higher doses. Epidemiological studies tend to support an anxiolytic effect from the consumption of either  CBD or THC, as well as whole plant cannabis. Conversely, the available human clinical studies demonstrate a common anxiogenic response to THC (especially at higher doses).

Conclusion

Based on current data, cannabinoid therapies (containing primarily CBD) may provide a more suitable treatment for people with pre-existing anxiety or as a potential adjunctive role in managing anxiety or stress-related disorders. However, further research is needed to explore other cannabinoids and phytochemical constituents present in cannabis (e.g. terpenes) as anxiolytic interventions. Future clinical trials involving patients with anxiety disorders are warranted due to the small number of available human studies.
Preferences and acceptability of law enforcement initiated referrals for people who inject drugs: a mixed methods analysis
Authors: Olgin Gabriella K. , Bórquez Annick , Baker Pieter , Clairgue Erika , Morales Mario , Bañuelos Arnulfo , Arredondo Jaime , Harvey-Vera Alicia , Strathdee Steffanie , Beletsky Leo , Cepeda Javier A.
Published: October 2020

Background

Law enforcement officers (LEOs) come into frequent contact with people who inject drugs (PWID). Through service referrals, LEOs may facilitate PWID engagement in harm reduction, substance use treatment, and other health and supportive services. Little is known about PWID and LEO attitudes and concerns about service referrals, however. The objective of this mixed-methods study was to examine the alignment of service referral preferences and acceptability among PWID and LEOs in Tijuana, Mexico.

Methods

We assessed service referral preferences and perceived likelihood of participation in health and social services, integrating data from structured questionnaires with 280 PWID and 306 LEOs, contextualized by semi-structured interviews and focus groups with 15 PWID and 17 LEOs enrolled in two parallel longitudinal cohorts in Tijuana, Mexico.

Results

Among potential service referral options, both PWID (78%) and LEOs (88%) most frequently cited assistance with drug- and alcohol-use disorders. Over half of PWID and LEOs supported including harm reduction services such as syringe service programs, overdose prevention, and HIV testing. The majority of PWID supported LEO referrals to programs that addressed basic structural needs (e.g. personal care [62%], food assistance [61%], housing assistance [58%]). However, the proportion of LEOs (30–45%) who endorsed these service referrals was significantly lower (p <  0.01). Regarding referral acceptability, 71% of PWID reported they would be very likely or somewhat likely to make use of a referral compared to 94% of LEOs reporting that they thought PWID would always or sometimes utilize them. These results were echoed in the qualitative analysis, although practical barriers to referrals emerged, whereby PWID were less optimistic that they would utilize referrals compared to LEOs.

Conclusions

We identified strong support for LEO service referrals among both LEO and PWID respondents, with the highest preference for substance use treatment. LEO referral programs offer opportunities to deflect PWID contact with carceral systems while facilitating access to health and social services. However, appropriate investments and political will are needed to develop an evidence-based (integrated) service infrastructure.
Mixed type of total anomalous pulmonary venous connection: diagnosis, surgical approach and outcomes
Authors: Xiang Ming , Wu Chun , Pan Zhengxia , Wang Quan , Xi Linyun
Published: October 2020

Purpose

To summarize the diagnosis and treatment of 13 patients with mixed-type total anomalous pulmonary venous connection (TAPVC) and propose another classification for mixed TAPVC.

Methods

A retrospective review of 13 patients with mixed TAPVC undergoing repair at a single institution was conducted between January 2010 and November 2019. The diagnosis of mixed-type TAPVC was made in all patients using echocardiography combined with computed tomography angiography. According to the mixed TAPVC anatomy, there were 3 patients with type I TAPVC (2 + 2 veins), 10 patients with type II TAPVC (3 + 1 veins) and no patients with type III TAPVC. Correspondingly, there was 1 patient with the “SVC + VV” subtype, 2 patients with the “CS + C” subtype, 8 patients with the “CS + VV” subtype, 1 patient with the “CS + SVC” subtype and 1 patient with the “RA + SVC” subtype according to our classification system. All patients underwent cardiopulmonary bypass surgery.

Results

The median weight at surgery was 4.6 ± 1.0 kg (3.4–7.3 kg), and the median age at surgery was 96.2 ± 81.2 days (10–242 days). The median cardiopulmonary bypass time was 132.7 ± 25.1 min (range, 100 to 190 min). The cross-clamping time was 69.2 ± 14.4 min (range, 45 to 88 min). The hospital mortality rate was 7.7% (1 of 13), with late mortality occurring in 1 patient because of pulmonary venous obstruction (PVO) 7 months after surgery. The average follow-up after surgery was 3.4 ± 2.2 years (range, 5 months to 8 years). The survival rates at 3 and 5 years were both 90.9% ± 8.7% (95% CI: 73.8–108%). All remaining surviving patients were asymptomatic.

Conclusion

Mixed TAPVC can be repaired with good results in children and can be correctly diagnosed with echocardiography combined with computed tomography angiography. The classification system we propose is pragmatic and can guide the surgical approach.
Effect of dexmedetomidine on intraoperative Surgical Pleth Index in patients undergoing video-assisted thoracoscopic lung lobectomy
Authors: Wang Yu-Lan , Kong Xiao-Qi , Ji Fu-Hai
Published: October 2020

Background

The Surgical Pleth Index (SPI) is a monitoring method that reflects painful stimuli during general anesthesia, and dexmedetomidine is an analgesic adjuvant with an opioid-sparing effect. But up to now, it is still unclear whether dexmedetomidine has any influence on SPI. To investigate whether dexmedetomidine has an effect on SPI during video-assisted thoracoscopic surgery.

Methods

We enrolled 94 patients who underwent video-assisted thoracoscopic lung lobectomy. Patients were randomly assigned to a dexmedetomidine group (dexmedetomidine: 0.8 μg/kg administered for 10 min before anesthesia) or normal saline group (equal volume of normal saline). SPI and vital signs were recorded. The number rating scale (NRS) pain score was also evaluated.

Results

SPI values were significantly lower in the dexmedetomidine group than in the normal saline group at intubation and at discharge from the postanesthesia care unit. Compared with the normal saline group, mean arterial pressure and heart rate were both significantly lower in the dexmedetomidine group at intubation. Heart rate was lower at skin incision in the dexmedetomidine group. The NRS score in the normal saline group was noticeably higher vs. the dexmedetomidine group at discharge from the postanesthesia care unit.

Conclusions

Dexmedetomidine decreased intraoperative SPI and NRS scores. Our results showed that dexmedetomidine attenuated noxious stimuli.

Trial registration

Chinese Clinical Trial Registry (ChiCTR): ChiCTR-OOC-16009450, Registered 16 October, 2016.
Children at risk: A nation-wide, cross-sectional study examining post-traumatic stress symptoms in refugee minors from Syria, Iraq and Afghanistan resettled in Sweden between 2014 and 2018
Authors: Solberg Øivind , Nissen Alexander , Vaez Marjan , Cauley Prue , Eriksson Anna-Karin , Saboonchi Fredrik
Published: October 2020

Background

The objective of the present study was to assess nation-wide, representative prevalence estimates for symptom-defined posttraumatic stress disorder (PTSD) within populations of refugee minors from Afghanistan, Syria and Iraq resettled in Sweden.

Methods

A nation-wide, cross-sectional, questionnaire study with a stratified sample of refugee minors, aged 16–18 years, from Afghanistan, Iraq and Syria, resettled in Sweden between 2014 and 2018 (N = 5071) was conducted. The response rate was 22.3%, leaving n = 1129 refugee minors (boys 53.1% / girls 46.9%) in the final sample. Symptom-defined prevalences of PTSD were measured using CRIES-8 with ≥17 as cut-off. Data were analyzed using frequency distributions, and strata-specific PTSD prevalences with 95% confidence intervals (95% CIs), were estimated. The association between migratory status on arrival (unaccompanied vs. accompanied) and PTSD was estimated using crude and adjusted odds ratios (OR) utilizing logistic regression analyses with 95% CIs.

Results

Overall, the weighted PTSD prevalence was 42% (95% CI 38.9–45.1), with minors from Afghanistan presenting the highest prevalence (56.9, 95% CI 51.5–62.2), compared to minors from Iraq (36.8, 95% CI 28.9–45.4) and Syria (33.4, 95% CI 29.4–37.6). Unaccompanied minors from Afghanistan had higher odds of PTSD compared to accompanied minors from Afghanistan (OR = 1.92, 95% CI 1.08–3.40). Gender differences were non-significant.

Conclusions

High prevalences of symptom-defined PTSD among refugee minors in general and in unaccompanied minors from Afghanistan in particular, were revealed. Findings calls for continued efforts to support this especially vulnerable group.
Severe COVID-19 virus reactivation following treatment for B cell acute lymphoblastic leukemia
Authors: Lancman Guido , Mascarenhas John , Bar-Natan Michal
Published: October 2020

SARS-CoV-2 has infected millions of people worldwide, but little is known at this time about second infections or reactivation. Here, we report a case of a 55-year-old female undergoing treatment for CD20+ B cell acute lymphoblastic leukemia who experienced a viral reactivation after receiving rituximab, cytarabine, and dasatinib. She was initially hospitalized with COVID-19 in April and developed a high antibody titer with two negative nasal polymerase chain reaction (PCR) swabs for SARS-CoV-2 on discharge. After recovery, she resumed treatment in June for her leukemia, which included rituximab, cytarabine, and dasatinib. She promptly lost her COVID-19 antibodies, and her nasal PCR turned positive in June. She developed a severe COVID-19 pneumonia with lymphopenia, high inflammatory markers, and characteristic bilateral ground-glass opacities on chest CT, requiring high-flow nasal cannula and transfer to the intensive care unit. She received steroids, anticoagulation, and convalescent plasma, and within 48 h she was off oxygen. She was discharged home in stable condition several days later. Given the short time frame from leukemia treatment to PCR positivity and the low case rate in mid-June in New York City, reinfection appears to have been unlikely and SARS-CoV-2 reactivation is a possible explanation. This case illustrates the risks of treating recently recovered COVID-19 patients with immunosuppressive therapy, particularly lymphocyte- and antibody-depleting therapy, and raises new questions about the potential of SARS-CoV-2 reactivation.
Long non-coding RNA LPP-AS2 promotes glioma tumorigenesis via miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop
Authors: Zhang Xiaoming , Niu Wanxiang , Mu Maolin , Hu Shanshan , Niu Chaoshi
Published: October 2020

Background

Glioblastoma is the most common primary malignant intracranial tumor with poor clinical prognosis in adults. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) function as important regulators in cancer progression, including glioblastoma. Here, we identified a new lncRNA LPP antisense RNA-2 (LPP-AS2) and investigated its function and mechanism in the development of glioma.

Methods

High-throughput RNA sequencing was performed to discriminate differentially expressed lncRNAs and mRNAs between glioma tissues and normal brain tissues. Expression of LPP-AS2, epidermal growth factor receptor (EGFR) and miR-7-5p in glioma tissues and cell lines was detected by real-time quantitative PCR (RT-qPCR), and the functions of lncRNA LPP-AS2 in glioma were assessed by in vivo and in vitro assays. Insight into the underlying mechanism of competitive endogenous RNAs (ceRNAs) was obtained via bioinformatic analysis, dual luciferase reporter assays, RNA pulldown assays, RNA immunoprecipitation (RIP) and rescue experiments.

Results

The results of high-throughput RNA-seq indicated lncRNA LPP-AS2 was upregulated in glioma tissues and further confirmed by RT-qPCR. Higher LPP-AS2 expression was related to a poor prognosis in glioma patients. Based on functional studies, LPP-AS2 depletion inhibited glioma cell proliferation, invasion and promoted apoptosis in vitro and restrained tumor growth in vivo, overexpression of LPP-AS2 resulted in the opposite effects. In addition, LPP-AS2 and EGFR were observed in co-expression networks. LPP-AS2 was found to function as a ceRNA to regulate EGFR expression by sponging miR-7-5p in glioma cells. The result of chromatin immunoprecipitation (ChIP) assays validated that c-MYC binds directly to the promoter region of LPP-AS2. As a downstream protein of EGFR, c-MYC was modulated by LPP-AS2 and in turn enhanced LPP-AS2 expression. Thus, lncRNA LPP-AS2 promoted glioma tumorigenesis via a miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop.

Conclusions

Our study elucidated that LPP-AS2 acted as an oncogene through a novel molecular pathway in glioma and might be a potential therapeutic approach for glioma diagnosis, therapy and prognosis.
Characterization of universal features of partially methylated domains across tissues and species
Authors: Decato Benjamin E. , Qu Jianghan , Ji Xiaojing , Wagenblast Elvin , Knott Simon R. V. , Hannon Gregory J. , Smith Andrew D.
Published: October 2020

Background

Partially methylated domains (PMDs) are a hallmark of epigenomes in reproducible and specific biological contexts, including cancer cells, the placenta, and cultured cell lines. Existing methods for deciding whether PMDs exist in a sample, as well as their identification, are few, often tailored to specific biological questions, and require high coverage samples for accurate identification.

Results

In this study, we outline a set of axioms that take a step towards a functional definition for PMDs, describe an improved method for comparable PMD detection across samples with substantially differing sequencing depths, and refine the decision criteria for whether a sample contains PMDs using a data-driven approach. Applying our method to 267 methylomes from 7 species, we corroborated recent results regarding the general association between replication timing and PMD state, and report identification of several reproducibly “escapee” genes within late-replicating domains that escape the reduced expression and hypomethylation of their immediate genomic neighborhood. We also explored the discordant PMD state of orthologous genes between human and mouse, and observed a directional association of PMD state with gene expression and local gene density.

Conclusions

Our improved method makes low sequencing depth, population-level studies of PMD variation possible and our results further refine the model of PMD formation as one where sequence context and regional epigenomic features both play a role in gradual genome-wide hypomethylation.
Generation of cortical neurons through large-scale expanding neuroepithelial stem cell from human pluripotent stem cells
Authors: Zhao Shumei , Duan Kui , Ai Zongyong , Niu Baohua , Chen Yanying , Kong Ruize , Li Tianqing
Published: October 2020

Background

Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into cortical neurons for disease modeling and regenerative medicine. However, these procedures are hard to provide sufficient cells for their applications. Using a combination of small-molecules and growth factors, we previously identified one condition which can rapidly induce hPSCs into neuroepithelial stem cells (NESCs). Here, we developed a scalable suspension culture system, which largely yields high-quality NESC-spheres and subsequent cortical neurons.

Methods

The NESC medium was first optimized, and the suspension culture system was then enlarged from plates to stirred bioreactors for large-scale production of NESC-spheres by a stirring speed of 60 rpm. During the expansion, the quality of NESC-spheres was evaluated. The differentiation potential of NESC-spheres into cortical neurons was demonstrated by removing bFGF and two pathway inhibitors from the NESC medium. Cellular immunofluorescence staining, global transcriptome, and single-cell RNA sequencing analysis were used to identify the characteristics, identities, purities, or homogeneities of NESC-spheres or their differentiated cells, respectively.

Results

The optimized culture system is more conducive to large-scale suspension production of NESCs. These largely expanded NESC-spheres maintain unlimited self-renewal ability and NESC state by retaining their uniform sizes, high cell vitalities, and robust expansion abilities. After long-term expansion, NESC-spheres preserve high purity, homogeneity, and normal diploid karyotype. These expanded NESC-spheres on a large scale have strong differentiation potential and effectively produce mature cortical neurons.

Conclusions

We developed a serum-free, defined, and low-cost culture system for large-scale expansion of NESCs in stirred suspension bioreactors. The stable and controllable 3D system supports long-term expansion of high-quality and homogeneous NESC-spheres. These NESC-spheres can be used to efficiently give rise to cortical neurons for cell therapy, disease modeling, and drug screening in future.
UBA2 activates Wnt/β-catenin signaling pathway during protection of R28 retinal precursor cells from hypoxia by extracellular vesicles derived from placental mesenchymal stem cells
Authors: Koh Kyungmin , Park Mira , Bae Eun Soo , Duong Van-An , Park Jong-Moon , Lee Hookeun , Lew Helen
Published: October 2020

Background

Stem cell transplantation has been proposed as an alternative treatment for intractable optic nerve disorders characterized by irrecoverable loss of cells. Mesenchymal stem cells, with varying tissue regeneration and recovery capabilities, are being considered for potential cell therapies. To overcome the limitations of cell therapy, we isolated exosomes from human placenta-derived mesenchymal stem cells (hPMSCs) and investigated their therapeutic effects in R28 cells (retinal precursor cells) exposed to CoCl2.

Method

After 9 h of exposure to CoCl2, the hypoxic damaged R28 cells were divided into the non-treatment group (CoCl2 + R28 cells) and treatment group (CoCl2 + R28 cells treated with exosome). Immunoblot analysis was performed for Pcna, Hif-1α, Vegf, Vimentin, Thy-1, Gap43, Ermn, Neuroflament, Wnt3a, β-catenin, phospo-GSK3β, Lef-1, UBA2, Skp1, βTrcp, and ubiquitin. The proteomes of each group were analyzed by liquid chromatography/tandem mass (LC-MS/MS) spectrometry. Differentially expressed proteins (DEPs) were detected by label-free quantification, and the interactions of the proteins were examined through signal transduction pathway and gene ontology analysis.

Result

We observed that exosome could significantly recover proliferation damaged by CoCl2 treatment. In addition, the treatment group presented the decreased expression of Hif-1α protein (P < 0.05) and increased expression of proliferation marker, Pcna, and nerve regeneration-related factors such as Vimentin, Thy-1, and Neuroflament (P < 0.05) compared with the non-treatment group. In total, 200 DEPs were identified in the non-treatment group and treatment group (fold change ≥ 2, p < 0.05). Catenin and ubiquitin systems (UBA2, UBE2E3, UBE2I) were found in both the DEP lists of downregulated proteins from the non-treatment group and upregulated proteins from the treatment group. The mRNA expressions of ubiquitin systems were significantly decreased under hypoxic conditions. Moreover, UBA2 and Wnt/β-catenin protein were associated with the rescue of the hypoxic damaged R28 cells. Using a siRNA system, we could find it out that hPMSC exosomes could not repair altered expressions of target proteins by CoCl2 in lacking UBA2 R28 cells.

Conclusion

This study reported that hypoxic damaged expression of regeneration markers in R28 cells was significantly recovered by hPMSC exosomes. We could also demonstrate that UBA2 played a key role in activating the Wnt/β-catenin signaling pathway during protection of hypoxic damaged R28 cells, induced by hPMSC exosomes.
Acquisition of cancer stem cell properties in osteosarcoma cells by defined factors
Authors: Fujiwara Shuichi , Kawamoto Teruya , Kawakami Yohei , Koterazawa Yasufumi , Hara Hitomi , Takemori Toshiyuki , Kitayama Kazumichi , Yahiro Shunsuke , Kakutani Kenichiro , Matsumoto Tomoyuki , Matsushita Takehiko , Niikura Takahiro , Koyanagi-Aoi Michiyo , Aoi Takashi , Kuroda Ryosuke , Akisue Toshihiro
Published: October 2020

Background

Cancer stem cells (CSCs) are considered to be responsible for tumor initiation, formation, and poor prognosis of cancer patients. However, the rarity of CSCs in clinical samples makes it difficult to elucidate characteristics of CSCs, especially in osteosarcoma (OS). The aim of this study is to verify whether it is possible to generate CSC-like cells by transducing defined factors into an OS cell line.

Methods

We retrovirally transduced the Octamer-binding transcription factor 3/4 (OCT3/4), Kruppel-like factor 4 (KLF4), and SRY-box transcription factor 2 (SOX2) genes into the MG-63 human OS cell line (MG-OKS). Parental and GFP-transduced MG-63 cells were used as negative control. We assessed the properties of the generated cells in vitro and in vivo. Multiple comparisons among groups were made using a one-way analysis of variance (ANOVA) followed by post hoc testing with Tukey’s procedure.

Results

MG-OKS cells in vitro exhibited the significantly increased mRNA expression levels of CSC markers (CD24,CD26, andCD133), decreased cell growth, increased chemoresistance and cell migration, and enhanced sphere formation. Notably, MG-OKS cells cultured under osteogenic differentiation conditions showed strongly positive staining for both Alizarin Red S and alkaline phosphatase, indicating osteogenesis of the cells. Gene ontology analysis of microarray data revealed significant upregulation of epidermal-related genes. Tumors derived from MG-OKS cells in vivo were significantly larger than those from other cells in μCT analysis, and immunohistochemical staining showed that Ki-67, osteocalcin, and HIF-1α-positive cells were more frequently detected in the MG-OKS-derived tumors.

Conclusions

In this study, we successfully generated OS CSC-like cells with significantly enhanced CSC properties following transduction of defined factors.
Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration
Authors: Kawakita Naoya , Toba Hiroaki , Miyoshi Keiko , Sakamoto Shinichi , Matsumoto Daisuke , Takashima Mika , Aoyama Mariko , Inoue Seiya , Morimoto Masami , Nishino Takeshi , Takizawa Hiromitsu , Tangoku Akira
Published: October 2020

Background

Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles.

Methods

BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated.

Results

Flow cytometric analysis revealed that BASCs represented ~ 7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs.

Conclusions

Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.