bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast Cancer Therapeutics Based on Fusarochromanone and EGFR Inhibitors
Authors: Carroll Natalie , Smith Alena , Salvatore Brian A. , Mahdavian Elahe
Published: March 2021

Background: Fusarochromanone (FC101) is a small molecule with potent anti-cancer activity. It was originally derived from the fungal plant pathogen, Fusarium equiseti, and it has also been synthesized in non-racemic form in our lab. Numerous studies reveal the promising biological activity of FC101, including potent anti-angiogenic and anti-cancer activity. While FC101 is potent as a single drug treatment across many cancer cell lines, current cancer therapies often incorporate a combination of drugs in order to increase efficacy and decrease the development of drug resistance. In this study, we leverage drug combinations and cellular phenotypic screens to address important questions about FC101’s mode of action and its potential synergies as an anti-cancer therapeutic agent in triple negative breast cancer (TNBC).Method: We hypothesized that FC101’s activity against TNBC is similar to the known mTOR inhibitor, everolimus, because FC101 reduces the phosphorylation of two key mTOR substrates, S6K and S6. Since everolimus synergistically enhances the anti-cancer activities of known EGFR inhibitors (erlotinib or lapatinib) in TNBC, we performed analogous studies with FC101. Phenotypic cellular assays helped assess whether FC101 (in both single and combination treatments) acts similarly to everolimus.Results: FC101 outperformed all other single treatments in both cell proliferation and viability assays. Unlike everolimus, however, FC101 brought about a sustained decrease in cell viability in drug washout studies. None of the other drugs were able to maintain comparable effects upon removal of the treatment agents. Although we observed slightly additive effects when the TNBC cells were treated with FC101 and either EGFR inhibitor, those effects were not truly synergistic in the manner displayed with everolimus. Conclusion: Our results rule out direct inhibition of mTOR by FC101 and suggest that FC101 acts through a different mechanism than everolimus. This lays the foundation for the refinement of our hypothesis in order to better understand FC101’s mode of action as a novel anti-cancer agent.
A new discovery of genetic polymorphisms of important genes in WNT pathway (LPR5 and AXIN1) associated with osteoporosis susceptibility in Chinese Han population
Authors: Cui Yongsheng , Hu Xinglv , Zhang Chen , Wang Kunzheng
Published: March 2021

Background: genetic factors play a critical role in the pathogenesis of osteoporosis. The imbalance of WNT/β-catenin will cause the occurrence of osteoporosis. LPR5 and AXIN1 play an important role in the classical Wnt/β-catenin signaling pathway. Our study was aimed to determine the association between 5 candidate single nucleotide polymorphisms (SNPs) of LPR5 or AXIN1 and osteoporosis susceptibility in Chinese Han population. Methods: the association analysis was conducted between 5 candidate SNPs and osteoporosis susceptibility among 1198 participants. Agena MassARRAY was used to genotype SNPs. The association between SNPs and osteoporosis susceptibility in different genetic models was analyzed by logistic regression analysis. Multi-factor dimension reduction (MDR) was used to analyze the interaction of SNP-SNP in the osteoporosis risk. The difference of clinical indicators under different genotypes was completed by one-way analysis of variance.Results: we found that LPR5 rs11228240, AXIN1 rs2301522 and rs9921222 were significantly associated with the osteoporosis susceptibility. The results of subgroup analysis showed that LPR5 rs11228240 (protective factor) and AXIN1 rs2301522 (risk factor) were significantly associated with the susceptibility of osteoporosis among participants who were age > 60 years, female or BMI≤24; AXIN1 rs9921222 significantly increased the risk of osteoporosis among participants with BMI≤24. The results of Haplotype analysis showed that Ars2301522Crs9921222 could increase the susceptibility of osteoporosis. We also found that LRP5 rs11228219, AXIN1 rs2301522 and rs9921222 showed a potential association with some clinical indicators of osteoporosis.Conclusion: the SNPs of LPR5 and AXIN1 which are important genes in WNT classical pathway, have a potential association with osteoporosis susceptibility in Chinese Han population.
Rate of Decline in Kidney Function and Age-of-Onset or Duration of Type 2 Diabetes
Authors: Buyadaa Oyunchimeg , Salim Agus , Morton Jedidiah I , Magliano Dianna J , Shaw Jonathan E
Published: March 2021

The association between rate of kidney function decline and age-of-onset or duration of type 2 diabetes has not been well investigated. We aimed to examine whether rates of estimated glomerular filtration rate (eGFR) decline differ by age-of-onset or duration in people with type 2 diabetes. Using the Action to Control Cardiovascular Risk in Diabetes study dataset rates of eGFR decline were calculated using a joint-longitudinal-survival model and were compared among groups defined by the age-of-onset (0–39, 40–49, 50–59, 60–69 and > 70 years) and 5-year diabetes duration intervals. Changes in renal function were evaluated using median of 6 (interquartile range: 3–10) eGFR measurements per person. eGFR decline was the slowest in those with an age-at-diagnosis of 50 − 59 years or those with duration of diabetes < 5 years. The rates of eGFR decline were significantly greater in those with an age-of-onset < 40 years or those with duration of diabetes > 20 years compared to those diagnosed at 50 − 59 or those with duration of diabetes < 5 years (-1.98 vs -1.61 ml/min/year; -1.82 vs -1.52 ml/min/year; respectively (p < 0.001). Those with youngest age-of-onset or longest duration of type 2 diabetes had more rapid declines in eGFR compared to those diagnosed at middle age or those with shorter duration of diabetes.
Parthenolide induces autophagy and apoptosis of breast cancer cells associated with the PI3K/AKT/mTOR pathway
Authors: Han Yanyan , Yang Jinfeng , Sun Yan , Fan Shujun , Lu Ying , Li Lianhong
Published: March 2021

Background: Breast cancer is an aggressive malignancy that is unresponsive to conventional therapies. Parthenolide has been demonstrated to have anticancer effects against various types of cancer, including breast cancer. The aim of the present study was to investigate the effect and underlying mechanism of parthenolide in human breast cancer. Methods: Autophagy was measured through immunofluorescence and western blotting. DAPI staining and flow cytometry analysis were used to measure apoptosis. Western blot analysis was used to investigate the mechanism of autophagy induced by parthenolide on the expression levels of phosphoinositide 3‑kinase (PI3K), AKT, phosphorylated (p‑) AKT, mammalian target of rapamycin (mTOR), ATG13 and ATG14. Furthermore, apoptosis was confirmed via western blot analysis. Conclusion: Parthenolide inhibits breast cancer cell proliferation and induces autophagy and apoptosis, and suggested that the PI3K/AKT/mTOR pathway serves an important role in autophagy and apoptosis.
Novel neutralizing human monoclonal antibodies against tetanus neurotoxin
Authors: Minamitani Takeharu , Kiyose Karin , Otsubo Ryota , Ito Toshihiro , Akiba Hiroki , Furuta A. Rika , Inoue Tsuyoshi , Tsumoto Kouhei , Satake Masahiro , Yasui Teruhito
Published: March 2021

Tetanus is a fatal disease caused by tetanus neurotoxin (TeNT). TeNT is composed of a light chain (Lc) and a heavy chain, the latter of which is classified into two domains, N-terminus Hn and C-terminus Hc. Several TeNT-neutralizing antibodies have been reported, but it remains unclear which TeNT domains are involved in neutralization. To further understand the mechanism of these antibodies, we isolated TeNT-reactive human antibody clones from peripheral blood mononuclear cells. We then analyzed the reactivity of the isolated antibody clones to each protein domain and their inhibition of Hc-ganglioside GT1b binding, which is critical for TeNT toxicity. We also investigated the TeNT-neutralizing ability of isolated antibody clones and showed that Hn-reactive clones protected strongly against TeNT toxicity in mice. Furthermore, combination treatment of Hn-reactive antibody clones with both Hc-reactive and TeNT mix–reactive antibody clones enhanced the neutralizing effect. These results indicated that antibody clones targeting Hn effectively neutralized TeNT. In addition, the use of a cocktail composed of Hc-, Hn-, and TeNT mix–reactive antibodies provided enhanced protection compared to the use of each antibody alone.
Evaluation of a revised resuscitation protocol for out-of-hospital cardiac arrest patients due to COVID-19 safety protocols: A single-center retrospective study in Japan
Authors: Kandori Kenji , Okada Yohei , Ishii Wataru , Narumiya Hiromichi , Iizuka Ryoji
Published: March 2021

Background: This study aimed to determine the association between cardiopulmonary resuscitation (CPR) under the coronavirus 2019 (COVID-19) safety protocols in our hospital and the prognosis of out-of-hospital cardiac arrest (OHCA) patients, in an urban area tertiary critical care center, where the prevalence of COVID-19 infection is relatively low.Methods: This was a single-center, retrospective, observational, cohort study conducted at a tertiary critical care center in Kyoto City, Japan. Adult OHCA patients were included who were admitted to our emergency department while still in cardiac arrest at hospital arrival between January 1, 2019, and December 31, 2020. Our hospital implemented a revised resuscitation protocol for OHCA patients on April 1, 2020 to prevent COVID-19 disease transmission. This study defined the conventional CPR period as January 1, 2019 to March 31, 2020, and the COVID-19 safety protocol period as April 1, 2020 to December 31, 2020. The primary outcome was hospitalization survival. The secondary outcomes were return of spontaneous circulation after hospital admission and 1-month survival after OHCA occurrence. The adjusted odds ratios with 95% confidence intervals (CI) were calculated for outcomes to compare the two study periods, and the multivariable logistic model was used to adjust for six variables: age, presence of witness, presence of bystander CPR, initial cardiac rhythm at the scene, call–hospital interval, and the first documented cardiac rhythm at hospital arrival.Results: The study analyzed 443 patients, with a median age of 76 years (65–85), and included 261 men (58.9%). The percentage of hospitalization survivors during the entire research period was 16.9% (75/443 patients), with 18.7% (50/267) during the conventional CPR period and 14.2% (25/176) during the COVID-19 safety protocol period. The adjusted odds ratio for hospitalization survival during the COVID-19 safety protocol period was 0.61 (95% CI, 0.32–1.18), as compared with conventional CPR.Conclusions: There was no apparent difference in hospitalization survival between the OHCA patients resuscitated under the conventional CPR protocol compared with the current revised protocol for controlling COVID-19 disease transmission.
Osmotically Balanced, Large Unilamellar Liposomes for Sustained Bupivacaine Release: From the Development of Liposomes to Their in Vivo Application
Authors: Yoo Hyebin , Park Jun Seok , Oh Seung Soo , Kang Hyun
Published: March 2021

To efficiently prolong analgesic effects, we developed osmotically balanced, large unilamellar liposomes (~6 μm in diameter) in which highly concentrated bupivacaine (up to 30 mg/mL) was encapsulated, and their sustained bupivacaine release was highly effective in relieving postoperative pain over 24 h in a rat model. Our reverse-phase evaporation method based on non-toxic alcohol, ethanol, enabled simple and cost-effective production of bupivacaine-loaded liposomes, of which osmotic pressure was readily balanced to improve the structural stability of the enlarged unilamellar liposomes along with extension of their shelf life (> a month). The in vitro release profile verified that the release duration of the bupivacaine-loaded liposomes extended up to six days. For the in vivo study, male Sprague-Dawley rats were used for the incisional pain model, simulating postoperative pain, and the mechanical withdrawal threshold (MWT) was measured using a von Frey filament. Compared to the control group that received intraplantar administration of normal saline, the group of liposomal bupivacaine showed that the initially increased MWT gradually decreased up to 24 h, and importantly, the analgesic effect of the liposomal bupivacaine was maintained 6 times longer than that of bupivacaine only, proving the potential of effective long-acting anesthetics.
Socioeconomic factors contributing to antibiotic resistance in China: a panel data analysis
Authors: Zhen Xuemei , Chen Jingchunyu , Sun Xueshan , Sun Qiang , Guo Shasha , Lundborg Cecilia Stålsby
Published: March 2021

Background
The relationship between socioeconomic factors and ABR remains a knowledge gap in China. In this study, our aim was to examine the association between ABR proportion and socioeconomic factors across 30 provinces in mainland China.
Methods
We used two measures of ABR: the proportion of carbapenem-resistant Pseudomonas aeruginosa (CRPA), 3rd generation cephalosporin-resistant Klebsiella pneumoniae (3GCRKP), 3rd generation cephalosporin-resistant Escherichia coli (3GCREC), methicillin-resistant Staphylococcus aureus (MRSA); and the aggregate resistance. ABR proportion, education, gross domestic product (GDP) per capita, out-of-pocket (OOP) health expenditure, physician density, hospital bed density, access to water source, and number of public toilets per 10,000 population data during 2014 and 2018 in 30 provinces in mainland China were included. We examined the association between ABR level and potential contributing factors using panel data modelling. In addition, we explored this relationship from eastern, central, and western economic zone, respectively.
Results
Our results indicated that higher hospital bed density and physician density were significantly associated with lower levels of ABR. The issue of ABR was also related to socioeconomic factors such as GDP per capita, OOP health expenditure, education, which might depend on different resistant bacteria or different economic zones. GDP per capita was negatively associated with CRPA level, but positively associated with MRSA level. Higher OOP health expenditure was associated higher CRPA level. In addition, we only found that ABR prevalence was significantly negatively associated with education, and positively associated with OOP health expenditure in central economic zone, but not found in eastern and western economic zone.
Conclusions
Our study highlights that measures increasing hospital beds and physicians allocation to curb ABR should be implemented. Besides, intervention measures tackling the development and spread of ABR in China must better recognize and address the importance of social and economic determinants.
The effect of mobility restrictions on the SARS-CoV-2 diffusion: lessons from the first wave in Sweden, USA, France and Colombia.
Authors: Telle Olivier , Paul Richard , Benkimoun Samuel
Published: March 2021

The control of human mobility has quickly been targeted as a major leverage to contain the spread of SARS-CoV-2 in a great majority of countries worldwide. Using more than 151 million anonymized movements registered by one of the major social media platforms combined with spatial and temporal Covid-19 data, the objective of this research is to understand how mobility patterns and SARS-CoV-2 diffusion during the first wave are connected in four different countries: the west coast of the USA, Colombia, Sweden and France. In this research, we could demonstrate that introducing movement improved considerably the model. It underlines as well that mobility played an important role in the diffusion of SARS-CoV-2, even during the lockdown, suggesting a moderate impact of lockdown on virus diffusion. However, it suggests that government could better locate where disease mitigation would be the most effective by systematically analyzing real-time movements of population. Lockdown strategies and vaccination campaigns could, for example, be prioritized according to spatial vulnerability and connectivity to hotspots of viral circulation.
Differential Effects of Body Mass Index on Domain-Specific Cognitive Outcomes After Stroke
Authors: Lee Minwoo , Oh Mi Sun , Jung San , Lee Ju-Hun , Kim Chul-Ho , Jang Min Uk , Kim Young Eun , Bae Hee-Joon , Park Jaeseol , Kang Yeonwook , Lee Byung-Chul , Lim Jae-Sung , Yu Kyung-Ho
Published: March 2021

Background We aimed to investigate the association between body mass index (BMI) and domain-specific cognitive functions in post-ischemic stroke survivors.MethodsA total of 335 ischemic stroke patients were included in the study after completion of the Korean-Mini-Mental Status Examination (K-MMSE) and the K-VCIHS neuropsychological protocol at 3 months after stroke. Frontal lobe functions were analyzed using semantic/phonic fluency, processing speed, and mental set shifting. Our study participants were categorized into four groups according to BMI quartiles ResultsThe K-MMSE scores at 3 months differed significantly between the groups after adjustment for covariates with univariate p-value less than 0.1 (p = 0.003). Global cognitive function in stroke survivors in the Q1 BMI group was significantly lower than those in Q2 and Q4 BMI groups (K-MMSE scores, Q1: 22.9 ± 6.7 vs. Q2: 25.2 ± 5.2 and Q4: 25.1 ± 4.3). Controlled oral word association test findings indicated that phonemic and semantic word fluency was lower in Q4 BMI group participants than in Q2 BMI group participants (p = 0.012, and p=0.012 respectively). ConclusionsBMI might differentially affect cognitive domains after ischemic stroke. Although being underweight may negatively affect global cognition post-stroke, obesity could induce frontal lobe dysfunctions, specifically phonemic and semantic word fluency.
Optimizing reconstruction parameters for quantitative 124I-PET in the presence of therapeutic doses of 131I
Authors: Fanchon Louise , Beattie Brad , Pentlow Keith , Larson Steven , Humm John Laurence
Published: March 2021

Purpose To determine the accuracy of quantitative 124I PET imaging in the presence of therapeutic levels of 131I.Material and Methods Multiple PET images were acquired using a NEMA IEC phantom with spheres containing 0.4 MBq/cc of 124I and increasing amount of 131I activity in the phantom background (0 to 3.76 GBq). Acquisitions were performed on a GE Discovery 710 PET/CT scanner. At each 131I activity level two scans were acquired, one with the phantom at the center of the field of view (FOV) and one 11 cm off-center. Images were reconstructed with an ordered subset expectation maximization (OSEM) algorithm using between 1 and 25 iterations of 16 subsets. Results were evaluated visually and by comparing the 124I activity relative to the baseline PET performed in the absence of 131I.Results The presence of 131I within the PET FOV added to the random coincidence rate, to dead-time and to pile-up within the PET detectors. Using our standard clinical reconstruction parameters, the image quality and quantitative accuracy suffered at 131I background activities above 1.4 GBq. However, increasing the number of iterations resulted in dramatic improvements in image quality and quantitative accuracy. Projection space measurements suggest that the dead time corrections implemented on the scanner perform well even at the highest singles count rate tested (52 Mcps).Conclusion This study shows that 124I quantitative PET is feasible in the presence of large amounts of 131I on a GE D710. The high random coincidence fraction slows the reconstruction convergence rate, therefore iterations equivalent to at least 8x16 are recommended.
Immunomodulator FTY720 Rejuvenates β-cell and Ameliorates Cardiorenal Complications in Nonhuman Primate Model of Diabetes
Authors: Wang Yixin (Jim) , Wang Xiaoli , An Annie , Zang Mingfa , Xu Ling , Gong Kefeng , Xiao Yong-Fu , Yu Guoliang , Ma Zhongmin A.
Published: March 2021

Inadequate β-cell mass is essential for the pathogenesis of type 2 diabetes (T2D). Previous report showed that an immunomodulator FTY720, a sphingosine 1-phosphate (S1P) receptor modulator sustainably normalized hyperglycemia by stimulating β-cell in vivo regeneration in db/db mice. To further evaluate the therapeutic potential, we examined the effects of FTY720 on glucose homeostasis in a translational nonhuman primate (NHP) model of spontaneous diabetes. Daily administration of FTY720 (5 mg/kg) effectively lowered HbA1c, blood concentrations of fasting glucose (FBG) and insulin, hence, decreased homeostatic model assessment of insulin resistance (HOMA-IR); ameliorated glucose intolerance and restored glucose-stimulated insulin release, which was largely diminished in the vehicle-treated diabetic NHPs. Importantly, after discontinuation of FTY720, FBG and HbA1c remained at the reduced levels in washout period for 8 weeks. Accompanied by the glucose lowering effects, echocardiography revealed that FTY720 significantly improved cardiac left ventricular systolic function measured by increase in ejection fraction and fractional shortening, which was compromised in the diabetic NHPs. Finally, flow cytometry analysis detected that FTY720 significantly reduced CD4+ and increased DC cells. These data strongly suggest that immunomodulator FTY720 may be a novel immunotherapy to reverse T2D progression via rejuvenation of β-cell function with benefit to improve the cardiac function.
Stability of Flow Velocity and Intracoronary Resistance in the Intracoronary Electrocardiogram-triggered Pressure Ratio
Authors: Nakayama Masafumi , Tanaka Nobuhiro , Uchiyama Takashi , Ohkawauchi Takaaki , Tsuboko Yusuke , Iwasaki Kiyotaka , Kawase Yoshiaki , Matsuo Hitoshi
Published: March 2021

It has been found that the assessment of coronary artery lesions using the fractional flow reserve and instantaneous flow reserve measurements reduces the incidence of further cardiovascular events. Here, we investigated differences in the coronary flow velocity and resistance within the analysis interval between the instantaneous flow reserve (iFR) and the intracoronary electrocardiogram (IC-ECG)-triggered distal/aortic pressure (Pd/Pa) ratio (ICE-T). Thirty-three consecutive patients with stenoses that required coronary flow measurement were enrolled. ICE-T was defined as the average Pd/Pa ratio in the period corresponding to the isoelectric line of the IC-ECG. The index value, flow velocity, and intracoronary resistance during the analysis intervals of the iFR and ICE-T, both at rest and under hyperemia, were compared. The index value and intracoronary resistance of the ICE-T were found to be significantly lower, while the flow velocity was significantly higher, than those of the iFR (P < 0.001), and all fluctuations in ICE-T values were also significantly smaller than those in the iFR.In conclusion, the ICE-T is theoretically superior to pressure-dependent indices for analyzing phases with low and stable resistance, without an increase in invasiveness.
The influence of primary thyroid cancer to the prognosis of breast cancer: A SEER-based study
Authors: Chen Xinyue , Li Juanjuan , Wu Qi , Liu Hanqing , Yuan Jingping , Sun Shengrong
Published: March 2021

Purpose: Previous studies have revealed a potential link between breast cancer (BC) and thyroid cancer (TC). This study aimed to estimate the clinical characteristics of BC patients who also had primary TC, and to determine the effect of the sequence of the two malignancies on survival. Methods: We selected female patients with BC or TC in the Surveillance, Epidemiology, and End Results (SEER) database (2000 to 2012), and classified them as four cohorts, BC patients with a second TC (BC2TC cohort), TC patients with a second BC (TC2BC cohort), BC patients without TC (BC cohort) and TC patients without BC (TC cohort). Differences in clinical characteristics were analyzed using the chi-square test. The propensity score matching (PSM) method was performed to balance the baseline characteristics. The survival outcomes were analyzed using the Kaplan-Meier log-rank test. Multivariate Cox regression analyses were used to identify risk factors associated with overall survival (OS) and disease-specific survival (DSS). Results: After PSM, 1,260 pairs of patients with or without second primary TC were included in the survival analysis. The patients in BC2TC cohort had better OS (HR: 0.511(0.421-0.620), P<0.001) and DSS (HR: 0.458(0.346-0.606), P<0.001) than those in BC cohort. The subgroup analysis showed that OS was better in the BC2TC cohort in Luminal A and Luminal B subtypes (P<0.05). Conclusion: We found a second primary TC may improve the prognosis of BC patients, especially in women with Luminal breast cancer, while there was no such trend in TC patients with second BC.
Hoarseness After Shoulder Surgery in Beach-chair Position
Authors: Youn Seung-Min , Rhee Sung-Min , Kim Hwan Jin , Lee Hyun Woo , Moon Seong Cheol , Cho Soonghwan , Rhee Yong Girl
Published: March 2021

Background Isolated vocal cord palsy resulting hoarseness after shoulder surgery in beach-chair position had not been reported in literature to date. The purpose of this study was to review its incidence in our patient cohort, and identify any risk factors that may predispose the patient to the injury.Methods There were 10215 operative shoulder cases from January 2010 to December 2017. Inclusion criteria was any post-operative patients, whose operation was performed under general anesthesia in beach-chair position, who had the related symptoms, but the diagnoses had to be confirmed by otorhinolaryngologists with laryngoscopy studies. The affected patients’ clinical notes were retrospectively reviewed with the particular interest in the operative times, and the peri-operative cervical spine radiographs. The degree of cervical spine lordosis was assessed using a method described in literature, in which ‘absolute rotation angle’ (ARA) was measured. Results There were 8 reported cases of vocal cord injury in total (0.08%). Four were male patients and four were arthroscopic cases. The mean age was 59.4 ± 11.9 years old. No particular difficulties with positioning or intubation were documented. The average duration of anesthetic times was 141 minutes. On peri-operative cervical spine radiographs, the average lordosis was 8.2° (1.5° kyphosis - 21° lordosis), and except for one patient, all had ‘non-lordotic’ type curvatures. All but one patient had recovered fully with observation and expectant management, with the average recovery time being 19 weeks (range: 2 weeks to 1 year). Only patient who had not recovered during our 2-year follow-up period, had a ‘sigmoidal’ type cervical spine and was also managed with observation only.Conclusions The incidence of vocal cord injury with beach-chair positioning at our institution was low at 0.08%. The possible risk factors include long duration of the procedure and ‘non-lordotic’ cervical spine, as demonstrated by the trend in our study. Although rare, vocal cord injury has varying duration of recovery time, in the worst-case scenario being permanent, therefore it needs to be avoided by taking utmost care during positioning of the patient in beach-chair. Level of Evidence Level IV, case series
The Treatment of Anxiety in Patients with Somatoform Dysfunction, Reaction to Severe Stress and other Neurotic Disorders: A Multicenter Double-blind Placebo-controlled Randomized Trial
Authors: Parfenov Vladimir , Kamchatnov Pavel , Amelin Aleksandr , Barantsevich Evgeny , Khasanova Dina , Bogdanov Enver , Lokshtanova Tatiana , Maslova Natalya , Pizova Natalya , Kolokolov Oleg , Belskaya Galina , Kamenova Saltanat , Duchshanova Gulsum , Glazunov Alexey
Published: March 2021

The existing treatment of somatoform dysfunction (SD), reaction to severe stress (RSS) and adjustment disorders (AjD) is insufficiently effective and safe. Anxiolytic drug Tenoten (Materia Medica Holding) is shown to be effective in clinical trials (CT). Objectives The aim of multicenter double-blind placebo-controlled randomized CT was to investigate the safety and efficacy of Tenoten in the anxiety treatment of adults with SD, RSS, AjD and other neurotic disorders (oNDs). Methods 390 adults with SD, RSS and AjD or oNDs with the Hospital Anxiety and Depression scale-anxiety (HADS-A) score≥11 were randomized into 4 groups (Tenoten group 14 tablets/day n=127; Tenoten group 3 8 tablets/day n=131, combined Placebo group 2+4 n= 132). The changes from baseline in the mean Hamilton Anxiety Rating Scale (HAM-A) score in groups 1 and 3 after 12 weeks was the primary outcome. Results The decrease in the HAM-A score from 18.81±5.81 to 7.26±4.63 (group 1) and from 18.38±4.3 to 6.40±4.02 (group 3) was observed post-treatment (p group 1/placebo =0.0055, p group 3/placebo <0.0001). The mean changes in the scores in the groups 1, 3 and the Placebo were 11.25, 11.91 and 9.71, respectively. In total, 46 AEs (28 AEs in the Tenoten groups, 18 in the Placebo) were registered in 37 patients (20 in the Tenoten groups, and 17 in the Placebo). No differences in frequency of AEs between groups were found. Conclusions Tenoten was shown to be significantly more effective than placebo in the anxiety treatment of adults with SD, RSS, AjD and oNDs (clinicaltrials.gov NCT03036293).
Validation of the medium and short version of CENSOPAS-COPSOQ: A psychometric study in the Peruvian population
Authors: Lucero-Perez Martha R. , Sabastizagal Iselle , Astete Jhon , Burgos Miguel Angel , Villarreal-Zegarra David , Moncada Salvador
Published: March 2021

Background: The presence of psychosocial risks at work is associated with mental and physical health issues in workers. The study aim was to adapt the COPSOQ-ISTAS21 Medium-Version to the Peruvian context and to develop a Short-Version of the instrument.Method: Cross-sectional design study. The COPSOQ-ISTAS21 Medium Version was used. A confirmatory factor analysis was performed to determine the internal structure of each subdimension (first-order) and dimension (second-order) using the Robust Maximum Likelihood estimation method, and classic fit indices in the literature (CFI, SRMR, RMSEA). Internal consistency was evaluated using the alpha and omega coefficients. A short version was developed based on the items with the highest factorial load and that reduce the factorial complexity.Results: A total of 1707 participants were evaluated. In the confirmatory factor analysis, the goodness-of-fit indices for seventeen of the 20 one-dimensional models (subdimensions) were identified; two subdimensions could not be evaluated because they presented only two items. When conducting a multidimensional analysis, we identified that all second-order models presented optimal goodness-of-fit indices, except “psychological demands at work”. The latter required adding four pairs of correlated errors to reach adequate fit values. Finally, a short version of only 31 items was designed from the items with optimal fit indices.Conclusions: The new adapted versions of COPSOQ-ISTAS21 were renamed CENSOPAS-COPSOQ. The CENSOPAS-COPSOQ is an instrument with sufficient evidence of validity and reliability in its medium and short version, which is why its use is recommended in Peruvian work centers to identify the evaluation and prevention of psychosocial risks at work in Peru.
Nutritional Composition and Mineral Elements Content Analyses of Lonicera fulvotomentosa Hsu et S. C. Cheng Grown in China
Authors: Jiang Xianghui , Xiao Longqian
Published: March 2021

Lonicera fulvotomentosa Hsu et S. C. Cheng (L. fulvotomentosa), a vine shrub found in Southwestern China, is used for treating epidemic fever and infectious diseases, such as SARS and Avian Influenza. Here, we investigated the chemical composition and nutritional content of dried flowers of L. fulvotomentosa grown in yellow loam and Karst landform soil in Guizhou, China. The moisture content in all samples varied from 3.25 to 3.63%, lipids from 7.76 to 9.93%, fiber from 6.93 to 7.34%, ashes from 12.32 to 12.76%, crude protein from 7.85 to 8.53%, and carbohydrates from 56.21 to 59.77%. Using inductively coupled plasma-mass spectroscopy (ICP-MS), the predominant mineral elements in the dried flowers were found to be calcium (297.34-351.26 mg/kg), potassium (132.56-140.37 mg/kg), iron (37.77–41.25 mg/kg), and magnesium (9.47–11.36 mg/kg). Also, HPLC identified flavonoids (kaempferol, rutin, quercetin, luteolin, and apigenin) and phenolic acids (caffeic acid, gallic acid, and chlorogenic acid). Thus, the chemical composition of L. fulvotomentosa was similar to that of Lonicera japonica Thunb. (L. japonica). Thus, it could be used as an alternative to L. japonica. Our results showed that the dried flower of L. fulvotomentosa had an extremely high content of chlorogenic acids and caffeic acid, which could be developed as a candidate molecule as HIV inhibitors.
Do Gibbons Live in Dense Forest? A Case Study from Upper Brahmaputra Valley, Assam, India
Authors: Sarma Kuladip , Saikia Malabika Kakati , Sarania Bidyut , Basumatary Himolin , Baruah Siddhartha Sankar , Saikia Bhrigu Prasad , Kumar Awadhesh , Saikia Prasanta Kumar
Published: March 2021

The present study aimed at predicting the potential habitat of Western Hoolock Gibbon (Hoolock hoolock) in the upper Brahmaputra river valley, Assam and to identify the conservation priority areas for systematic conservation of the species taking canopy cover into account. We used the maximum entropy algorithm for the prediction of the potential habitat of Gibbons using its current distribution with 19 environmental parameters as primary predictors. Spatio-temporal analyses of the habitat were carried out using satellite-based remote sensing and GIS techniques for two decades (1998–2018) along with Terra Modis Vegetation Continuous Field product to examine the land use land cover (LULC), habitat fragmentation, Normalized Difference Vegetation Index (NDVI) and tree cover percentage of the study area. To identify the conservation priority area, we applied a cost-effective decision-making analysis using systematic conservation prioritization in R programming. The model predicted an area of 6025.1 km2 under high potential habitat, and a major part of it was found to overlap with the dense forest (80.04%) followed by moderately open forest (73.90%) and open forest (65.82%). The LULC change matrix showed deduction of forest areas in the predicted high potential habitat during the study period, while agricultural class showed an increasing trend. The fragmentation analysis indicated that the number of patches and patch density increased from 2008 to 2018 in the ‘very dense’ and ‘dense’ canopy regions of the gibbon habitat. Based on the conservation priority analysis, 640 km2 area has been proposed to conserve a minimum 10% of the gibbons’ habitat. The current analysis revealed that in Upper Brahmaputra Valley most of the areas under dense forest and dense canopy have remained intact over the last two decades, at least within the high potential habitat of gibbons independent of the degree of area change in forest, agriculture and plantation.
One-minute Sit-to-stand Test Is Practical to Assess and Follow the Muscle Weakness in Cystic Fibrosis.
Authors: Hardy Sophie , Berardis Silvia , Aubriot Anne-Sophie , Reychler Gregory , Gohy Sophie
Published: March 2021

Background: Quadriceps muscle weakness and reduced exercise tolerance are prevalent in patients with cystic fibrosis (CF) and associated with a worse prognosis. The one-minute sit-to-stand test (1STST) has been proposed to evaluate exercise capacity and assess quadriceps strength. The aim of the study was to correlate the 1STST and the maximal isometric voluntary contraction of the quadriceps (MVCQ) evaluated by the dynamometer in stable patients with CF and to evaluate the impact of intravenous (IV) antibiotherapy.Methods: MVCQ and exercise capacity (dynamometer and 1STST) were measured in stable patients with CF at a routine visit, at the admission and the discharge of an IV antibiotherapy. Patients wore an activity monitor during 72h during IV treatment. Results: 51 stable patients with CF at a routine visit and 30 treated with IV antibiotherapy were recruited. In stable patients, the number of repetitions was reduced to 2101nxkg±657 (mean±SD), representing 79% of the predicted values (%PV) (7;142) (median (min;max)) as well as the MVCQ to 78.64N-m (23.21;170.34), representing 57%PV±26. The 1STST was correlated to MVCQ (r=0.536;p<0.0001) and lung function (r=0.508;p=0.0001). Over the IV antibiotherapy course, the 1STST improves significantly like lung function and body mass index while a positive trend for MVCQ was observed. The gain of 1STST was correlated to the change in MVCQ (r=0.441;p=0.015) and was significantly higher in hospitalized patients versus home therapy.Conclusions: The 1STST is a good alternative to the dynamometer to evaluate and assess muscular weakness for the routine visit and IV antibiotherapy.
Effect of Napsin A and Circulating Tumor Cells with Mesenchymal Phenotype in Lung Adenocarcinoma
Authors: Wei Yu Hong , He yi Zhi
Published: March 2021

Objective: To evaluate the clinical significance of Napsin A and circulating tumor cells（CTCs）with mesenchymal phenotype (M-CTC) in lung adenocarcinoma(LUAD).Materials and Methods: Clinical data of 97 LUAD patients were retrieved. The CanPatrolTM CTC enrichment platform was used to isolate CTCs from the peripheral blood of LUAD patients. The protein expression of Napsin A in the tumor tissues was analyzed by immunohistochemistry. Results: 20 of the 97 patients (20.62%) were negative expression of Napsin A （Napsin A-）and 60 (61.86%) were M-CTC positive（M-CTC+). Both Napsin A expression (P=0.004) and M-CTC+ (P<0.001) showed significant correlation to lymphatic metastasis, and M-CTC+ was also significantly correlated with the tumor stage (P=0.009) but was not correlated with gender, age, smoking, tumor size and degree of differentiation. Furthermore, the Napsin A- patients had a higher positive rate of M-CTC. In addition, the recurrence-free survival (RFS; Log-rank P <0.001) and overall survival (OS; Log-rank P <0.001) of the M-CTC+ LUAD patients were significantly worse. Likewise, Napsin A- was also associated with poor RFS (Log-rank P <0.001) and OS (Log-rank P = 0.0003).Conclusion: LUAD patients with Napsin A- have a higher frequency of M-CTC+, and the Napsin A- and M-CTC+ status portends poor prognosis.
Double-Image Visually Meaningful Encryption Algorithm Based on Compressed Sensing and Frft Embedding
Authors: jiang donghua , Liu Lidong , Zhu Liya , Wang Xingyuan , Chen Yingpin , Rong Xianwei
Published: March 2021

The transmission of images via the Internet has grown exponentially in the past few decades. However, the Internet considered as an insecure method of information transmission may cause serious privacy issues. In order to overcome such potential security issues, a novel double-image visually meaningful encryption (DIVME) algorithm conjugating quantum cellular neural network (QCNN), compressed sensing (CS) and fractional Fourier transform (FRFT) is proposed in this paper. First, the wavelet coefficients of the two plain images are scrambled by the Fisher-Yates confusion algorithm, and then compressed by the key-controlled partial Hadamard matrix. The final meaningful cipher image is generated by embedding the encrypted images into a host image with the same resolution of the plain image via the FRFT-based embedding method. Besides, the eigenvalues of the plain images are utilized to generate the key stream to improve the ability of proposed DIVME algorithm to withstand the plaintext attacks. Afterwards, the plaintext eigenvalues are embedded into the alpha channel of the meaningful cipher image under control of the keys to reduce unnecessary storage space and transmission costs. Ultimately, the simulation results and security analyses indicate that the proposed DIVME algorithm is effective and can withstand multiple attacks.
Terahertz Time-domain Spectroscopy as a Novel Tool for Crystallographic Analysis in Cellulose: the Potentiality of Being a New Standard for Evaluating Crystallinity
Authors: Wang Han , Tsuchikawa Satoru , Inagaki Tetsuya
Published: March 2021

Given that terahertz (THz) radiation responds to intermolecular forces such as hydrogen bonds, THz time-domain spectroscopy (THz-TDS) has expanded possibilities in cellulose research. In this study, THz-TDS was used to investigate the crystallinity of three types of cellulose-based materials. Microcrystalline cellulose (MCC) and wood were ball milled at different times, and pseudo-wood was a mixture of MCC and lignin of different mass fractions. All the samples showed peaks at 3.04 THz in the THz mass absorption coefficient spectra. Further, the spectra from 2.79 THz to 3.32 THz were cut out and detrended by subtraction from a baseline. The integrated intensity of the detrended spectra showed a correlation with the mass fraction of lignin of the pseudo-wood samples, and ball milling time of the MCC and wood samples. The correlation was similar with the crystallinity index calculated from X-ray powder diffraction. Moreover, the original wood sample without ball milling had an integrated intensity that was about 30% that of the original MCC sample, matching with the cellulose concentration of the wood (about 30% to 40%). We normalized the integrated intensity of 2.79 THz to 3.32 THz into 1 to 0 by a min-max algorithm and proposed a new “index” for evaluating crystallinity.
Diversity of Ascomycetes Mushroom in Para Rubber Plantation, Thailand
Authors: Surawut Saowapha , Nak-aim Sorasak , Kunsook Chutapa , Kamhaengkul Laddawan , Kanjanavas Pornpimon , Yasawong Montri
Published: March 2021

Ascomycetes mushrooms are fungi that produce ascospores in asci and some with perithecia. Not only they have a role of decomposer in ecology but also produced some bioactive compound, anti-microbial activity, and cytotoxicity. This study aims to explore the diversity of ascomycetes mushroom species in para rubber plantations and to identify them by morphological and sequence analysis of the internal transcribed spacer (ITS) region. The results found ascomycetes mushroom consist of Trichoderma pezizoides (RP1, % identity 98.79, DQ835513.1), Daldinia eschscholtzii (RP2, % identity 100, MN310384.1), Cookeina sulcipes (RP3, % identity 98.44, KY094620.1), Cookeina garethjonesii (RP4, % identity 99.06, KY094622.1), Cookeina tricholoma (RP5, % identity 100, KY094619.1) and Xylaria terricola (RP6, % identity 88.42, MF577038.1). Most of the ascomycetes in this study have previously been described in Thailand except Xylaria terricola. Additionally, phylogenetic analysis of ascomycetes mushroom showed high genetic relatedness with reference strains. Therefore, the sequence similarity and phylogenetic analysis confirmed the identity of six ascomycetes mushroom species, and further study of bioactive compound from these mushrooms may be investigated for other applications.
Knockdown of 60S Ribosomal Protein L14-2 Reveals Their Potential Regulatory Roles in Enhancing Drought and Salt Tolerance in Cotton
Authors: shiraku Margaret , Magwanga Richard Odongo , Cai Xiaoyan , Kirungu Joy Nyangasi , Xu Yanchao , Mehari Teame Gereziher , Hou Yuqing , Wang Yuhong , Peng Renhai , Wang Kunbo , Zhou Zhongli , Fang Liu
Published: March 2021

BackgroundCotton is an important economic crop and the primary source of natural fiber. The effects of drought and salt stresses threaten strong fiber and large quantity production. However, due to the ever-changing climatic conditions, plants have evolved various mechanisms to cope with the effects of various stress factors. One of the plant's transcription factors with positive effects in alleviating effects of drought and salt stresses is the Ribosomal protein Large (RPL) gene families. This has prompted the functional characterization of the RPL14B gene previously identified in the QTL region as a candidate gene that responds to stress and initiates mechanisms that enhance stress tolerance. ResultsComprehensive identification and functional analysis were conducted in this study, in which 26, 8, and 5 proteins containing the RPL14B domain were identified in G. hirsutum, G. raimondii, and G. arboreum, respectively. Moreover, Cis-regulatory elements associated with the RPL genes were identified. The Myb binding sites (MBS), Myb, Abscisic acid-responsive element (ABRE), CAAT-box, TATA box, TGACG-motif, and CGTCA-motif responsive to Meja, and TCA- motif responsive to salicylic acid were identified. Validation of the candidate gene through virus-induced gene silencing (VIGS) revealed that the Gh_D01G0234 (RPL14B) knockdown significantly affected the cotton seedling's performance under drought/ salt stress conditions as evidenced by a significant reduction in various morphological and physiological traits. Moreover, antioxidant enzyme levels were significantly reduced in VIGS-plants, with substantially higher oxidant enzyme levels, as evidenced by the higher concentration level of Malondialdehyde (MDA). ConclusionThe results revealed the potential role of the gene, and it can be further exploited to breed climate-smart cotton varieties resilient to drought and salt stress conditions
Single-cell transcriptomic analysis elucidates APOE genotype specific changes across cell types in two brain regions in Alzheimer’s disease
Authors: Belonwu Stella , Li Yaqiao , Bunis Daniel , Rao Arjun Arkal , Solsberg Caroline Warly , Oskotsky Tomiko , Taubes Alice , Grone Brian , Zalocusky Kelly , Fragiadakis Gabriela , Huang Yadong , Sirota Marina
Published: March 2021

Alzheimer’s Disease (AD) is a complex neurodegenerative disease that gravely affects patients and imposes an immense burden on caregivers. Apolipoprotein E4 (APOE4) has been identified as the most common genetic risk factor for AD, yet the molecular mechanisms connecting APOE4 to AD are not well understood. Past transcriptomic analyses in AD have revealed APOE genotype-specific transcriptomic differences; however, these differences have not been explored at a single-cell level. Here, we leverage the first two single-nucleus RNA sequencing AD datasets from human brain samples, including nearly 55,000 cells from the prefrontal and entorhinal cortices. We observed more global transcriptomic changes in APOE4 positive AD cells and identified differences across APOE genotypes primarily in glial cell types. Our findings highlight the differential transcriptomic perturbations of APOE isoforms at a single-cell level in AD pathogenesis and have implications for precision medicine development in the diagnosis and treatment of AD.