bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychedelic Treatment for Trauma-Related Psychological and Cognitive Impairment Among US Special Operations Forces Veterans
Authors: Davis Alan K. , Averill Lynnette A. , Sepeda Nathan D. , Barsuglia Joseph P. , Amoroso Timothy
Published: July 2020

Background

U.S. Special Operations Forces Veterans are at increased risk for a variety of mental health problems and cognitive impairment associated with military service. Current treatments are lacking in effectiveness and adherence. Therefore, this study examined psychedelic treatment with ibogaine and 5-methoxy-N,N-dimethyltryptamine for trauma-related psychological and cognitive impairment among U.S. Special Operations Forces Veterans.

Method

We conducted a survey of Veterans who completed a specific psychedelic clinical program in Mexico between 2017 and 2019. Questions probed retrospective reports of mental health and cognitive functioning during the 30 days before and 30 days after treatment. A total of 65 people completed treatment during this time frame and were eligible for contact. Of these, 51 (78%) completed the survey and were included in data analyses (mean age = 40; male = 96%; married = 55%; Caucasian/White = 92%; Operation Enduring Freedom/Operation Iraqi Freedom Service = 96%).

Results

Results indicated significant and very large reductions in retrospective report of suicidal ideation (p < .001; d = −1.9), cognitive impairment (p < .001; d = −2.8), and symptoms of posttraumatic stress disorder (p < .001; d = −3.6), depression (p < .001; d = −3.7), and anxiety (p < .001; d = −3.1). Results also showed a significant and large increase in retrospective report of psychological flexibility (p < .001; d = 2.9) from before-to-after the psychedelic treatment. Increases in the retrospective report of psychological flexibility were strongly associated with retrospective report of reductions in cognitive impairment, and symptoms of posttraumatic stress disorder, depression, and anxiety (rs range −0.61 to −0.75; p < .001). Additionally, most participants rated the psychedelic experiences as one of the top five personally meaningful (84%), spiritually significant (88%), and psychologically insightful (86%) experiences of their lives. Limitations: Several limitations should be considered including the retrospective, self-report, survey design of the study, and the lack of randomization and blinding, thus making these finding preliminary.

Conclusion

U.S. Special Operations Forces Veterans may have unique treatment needs because of the sequela of problems associated with repeated trauma exposure and the nature of the exposure. Psychedelic-assisted therapy with these under-researched psychedelics may hold unique promise for this population. However, controlled studies are needed to determine whether this treatment is efficacious in relieving mental health and cognitive impairment among U.S. Special Operations Forces Veterans.
circCELSR1 facilitates ovarian cancer proliferation and metastasis by sponging miR-598 to activate BRD4 signals
Authors: Zeng Xiang-Yang , Yuan Jing , Wang Chen , Zeng Da , Yong Jia-Hui , Jiang Xiao-Yan , Lan Hua , Xiao Song-Shu
Published: July 2020

Background

Ovarian cancer is one of the most common gynecologic cancers and has high mortality rate due to the lack of early diagnosis method and efficient therapeutic agents. circCELSR1 is up-regulated in ovarian cancer, but its role and mechanisms in ovarian cancer are unclear.

Methods

Gene expression of circCELSR1, miR-598 and BRD4 in ovarian cells was examined by qRT-PCR. Protein level was determined by Western blotting. Bioinformatic analysis and luciferase assay determined the molecular binding among circCELSR1, miR-598 and BRD4 3′ UTR. Cell proliferation, migration, invasion and apoptosis were determined by colony formation, wound healing assay, transwell assay and flow cytometry analysis, respectively. An abdominal cavity metastasis nude mice model was used to determine the in vivo function of circCELSR1.

Results

circCELSR1 and BRD4 were promoted, but miR-598 was suppressed in various ovarian cancer cells. circCELSR1 bound to miR-598 and promoted expression of its downstream target BRD4. Knockdown of circCELSR1 suppressed proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), but promoted apoptosis in ovarian cancer cells, and these effects were reversed by miR-598 inhibition or BRD4 overexpression. circCELSR1 inhibition decreased the expression of BRD4 and its downstream proliferation/migration related genes by targeting miR-598. Furthermore, knockdown of circCELSR1 suppressed ovarian cancer growth and metastasis in nude mice.

Conclusion

Knockdown of circCELSR1 inhibited BRD4-mediated proliferation/migration related signaling via sponging miR-598, thereby repressing ovarian cancer progression. This study provides a new regulatory mechanism of ovarian cancer may facilitate the development of therapeutic agents for ovarian cancer.
Rubus apetalus (Rosaceae) improves spermatozoa characteristics, antioxidant enzymes and fertility potential in unilateral cryptorchid rats
Authors: Alumeti Munyali Désiré , Tetsatsi Momo Aimé Césaire , Bonsou Fozin Georges Romeo , Deeh Defo Patrick Brice , Petnga Tchatat Yannick , Lieunang Boris , Watcho Pierre
Published: July 2020

Background

Cryptorchidism (CPT) is an important cause of male infertility. Rubus apetalus is a medicinal plant with a powerful antioxidant potential. We investigated the effects of aqueous and methanolic extracts of R. apetalus on spermatozoa parameters, antioxidant enzymes and fertility potential of rats with experimental unilateral CPT.

Method

Normal (n = 15), sham-operated (n = 15) and cryptorchid rats (n = 80; distributed into 16 groups of 5 rats/group) were treated for 2, 4 or 8 weeks with either distilled water (10 ml/kg/day), vitamin E (75 mg/kg/day), aqueous or methanolic extract of R. apetalus (12 and 60 mg/kg). Sex organ weights, spermatozoa parameters, testicular proteins, sex hormones, fertility potential, morphometric characteristics of testis and oxidative stress markers were measured.

Results

CPT significantly (p < 0.05–0.001) decreased testicular and epididymal weights, spermatozoa density, spermatozoa motility, spermatozoa normality, testicular proteins, LH, FSH and testosterone concentrations. In cryptorchid rats, peri-vascular fibrosis significantly increased (p < 0.001), while diameter of the seminiferous tube, germ cell thickness, gestation index and fertility index decreased when compared to control. Additionally, CPT induced oxidative stress by increasing lipid peroxidation and by reducing superoxide dismutase and catalase activities. These alterations were corrected by R. apetalus. For instance, a significantly increase (p < 0.05–0.001) in spermatozoa motility, normality, viability and density after 2, 4 and 8 weeks of treatment was noticed. R. apetalus also increased (p < 0.05–0.001) testicular proteins, gestation index (90–100%) and fertility index (90–100%), compared to the untreated cryptorchid rats.

Conclusion

R. apetalus boosts fertility potential in cryptorchid rats and could be considered as a promising alternative agent for the management of infertility associated with CPT.
Matrine inhibits the growth of natural killer/T-cell lymphoma cells by modulating CaMKIIγ-c-Myc signaling pathway
Authors: Gu Jianyou , Zhang Yu , Wang Xiao , Xiang Jingjing , Deng Shu , Wu Dijiong , Chen Junfa , Yu Lihong , Zhou Yan , Wang Yaokun , Shen Jianping
Published: July 2020

Background

C-Myc overexpression is associated with poor prognosis and aggressive progression of natural killer/T-cell lymphoma (NKTCL). Matrine, a main alkaloid of the traditional Chinese herb Sophora flavescens Ait, has been shown to inhibit cellular proliferation and induce apoptosis of various cancer cells. The present study investigated the effects and possible mechanisms of matrine inhibiting the growth of natural killer/T-cell lymphoma cells.

Methods

The effects of matrine on the proliferation, apoptosis and expression of apoptotic molecules, STAT3, LMP1, RUNX3, EZH2 and activation of CaMKIIγ/c-Myc pathway were examined in cultured NKTCL cell line NK92 cells.

Results

In cultured NK92 cells, matrine inhibited the proliferation in a dose and time dependent manner. The IC50 value of matrine was 1.71 mM for 72 h post exposure in NK92 cells. Matrine induced apoptosis with decreased Bcl-2 expression and the proteasome-dependent degradation of c-Myc protein in NK92 cells. c-Myc protein half-life in NK92 was reduced from 80.7 min to 33.4 min after matrine treatment, which meant the stability of c-Myc was decreased after matrine exposure. Furthermore, we found that matrine downregulated c-Myc phosphorylation at Ser62 together with the inhibition of CaMKIIγ, a key regulator of c-Myc protein in NKTCL. The downregulation of c-Myc transcription by matrine was mediated through LMP1 inhibition. We also observed that anti-proliferative activity of matrine was irrelevant to STAT3, RUNX3 and EZH2.

Conclusions

The results of the present study indicated that matrine inhibits the growth of natural killer/T-cell lymphoma cells by modulating LMP1-c-Myc and CaMKIIγ-c-Myc signaling pathway.
Diagnostic anticipation to reduce emergency department length of stay: a retrospective cohort study in Ferrara University hospital, Italy
Authors: Strada Andrea , Bolognesi Niccolò , Manzoli Lamberto , Valpiani Giorgia , Morotti Chiara , Bravi Francesca , Bentivegna Roberto , Forini Elena , Pesci Antonella , Stefanati Armando , Di Ruscio Eugenio , Carradori Tiziano
Published: July 2020

Background

Emergency Department (ED) crowding reduces staff satisfaction and healthcare quality and safety, which in turn increase costs. Despite a number of proposed solutions, ED length of stay (LOS) - a main cause of overcrowding - remains a major issue worldwide.

This retrospective cohort study was aimed at evaluating the effectiveness on ED LOS of a procedure called “Diagnostic Anticipation” (DA), which consisted in anticipating the ordering of blood tests by nurses, at triage, following a diagnostic algorithm approved by physicians.

Methods

In the second half of 2019, the ED of the University Hospital of Ferrara, Italy, adopted the DA protocol on alternate weeks for all patients with chest pain, abdominal pain, and non-traumatic bleeding. A retrospective cohort study on DA impact was conducted. Using ED electronic data, LOS independent predictors (age, sex, NEDOCS and Priority Color Code, imaging tests, specialistic consultations, hospital admission) were evaluated through multiple regression.

Results

During the weeks when DA was adopted, as compared to control weeks, the mean LOS was shorter by 18.2 min for chest pain, but longer by 15.7 min for abdominal pain, and 33.3 for non-traumatic bleeding. At multivariate analysis, adjusting for age, gender, triage priority, specialist consultations, imaging test, hospitalization and ED crowding, the difference in visit time was significant for chest pain only (p < 0.001).

Conclusions

The impact of DA varied by patients’ condition, being significant for chest pain only. Further research is needed before the implementation, estimating the potential proportion of inappropriate blood tests and ED crowding status.
An application of analytic network process model in supporting decision making to address pharmaceutical shortage
Authors: Zarei Leila , Moradi Najmeh , Peiravian Farzad , Mehralian Gholamhosein
Published: July 2020

Background

The present study aimed to develop an Analytic Network Process (ANP) model to assist policymakers in identifying and prioritizing allocation indicators, which are being used or should be used to distribute drugs in short supply among different provinces.

Methods

The model encompasses the interactions between various indicators and efficiency, equity, and effectiveness paradigms. Accordingly, a set of clusters and elements, which were associated with the allocation of drugs in short supply in Iran’s pharmaceutical system, were detected to develop the model and were then compared in pairs in terms of a specified factor to show the priorities.

Results

Equity had the highest priority (0.459) following by Efficiency (0.37), and Effectiveness (0.171). The 4 most important allocation indicator were “number of prescriptions” (0.26) and “total bed occupancy rate” (0.19) related to equity, “total population” (0.21) in efficiency and “the burden of rare and incurable disease” (0.07) in effectiveness paradigm.

Conclusions

The capability to overcome inefficient resource allocation patterns caused by both oversupply and undersupply derived from historic resource allocation may be highly limited in the absence of the need indicators. The quality of the decision is related to a careful balancing act of the three paradigms which represents roughly the triple aim of public healthcare systems: clinical improvement (effectiveness), population health improvement (equity and access), and reducing cost (economic aspects -efficiency).
Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis
Authors: Jin Tian , Wu Di , Liu Xiao-Ming , Xu Jiang-Tao , Ma Bing-Jie , Ji Yun , Jin Yu-Ying , Wu Si-Yin , Wu Tao , Ma Ke
Published: July 2020

Background

Celastrol has been proven effective in anti-inflammatory but was limited in the clinic due to the poor solubility and side effects induced by low bioavailability. Osteoarthritis has acidic and inflammatory environment. Our aim was to load celastrol into HMSNs and capped with chitosan to construct a pH-responsive nanoparticle medicine (CSL@HMSNs-Cs), which is of high solubility for osteoarthritis intra-articular injection treatment.

Methods

The CSL@HMSNs-Cs were assembled and the characteristics were measured. The CSL@HMSNs-Cs was applied in vitro in the chondrocytes collected from rats cartilage tissue and in vivo in the MIA induced knee osteoarthritis rats via intra-articular injection. Cytotoxicity assay, pH-responsive release, pain behavior, MRI, safranin o fast green staining, ELISA and western blot analysis were applied to evaluate the bioavailability and therapeutic effect of CSL@HMSNs-Cs.

Results

CSL@HMSNs-Cs was stable due to the protection of the chitosan layers in alkaline environment (pH = 7.7) but revealed good solubility and therapeutic effect in acidic environment (pH = 6.0). The cytotoxicity assay showed no cytotoxicity at relatively low concentration (200 μg/mL) and the cell viability of chondrocytes stimulated by IL-1β was increased in CSL@HMSNs-Cs group. Paw withdrawal threshold in CSL@HMSNs-Cs group is increased, and MRI and Safranin O Fast Green staining showed improvements in articular surface erosion and joint effusion. The upregulated expression levels of IL-1β, TNF-α, IL-6, MMP-3 and MMP-13 and NF-κB signaling pathway of chondrocytes were inhibited in CSL@HMSNs-Cs group.

Conclusion

Hollow mesoporous silica nanoparticles were an ideal carrier for natural drugs with poor solubility and were of high biocompatibility for intra-articular injection. These intra-articular injectable CSL@HMSNs-Cs with improved solubility, present a pH-responsive therapeutic strategy against osteoarthritis.
Identification of six candidate genes for endometrial carcinoma by bioinformatics analysis
Authors: Zhu Yiming , Shi Liang , Chen Ping , Zhang Yingli , Zhu Tao
Published: July 2020

Background

Endometrial carcinoma (EC) is the most common gynecological malignant tumors which poses a serious threat to women health. This study aimed to screen the candidate genes differentially expressed in EC by bioinformatics analysis.

Methods

GEO database and GEO2R online tool were applied to screen the differentially expressed genes (DEGs) of EC from the microarray datasets. Protein-protein interaction (PPI) network for the DEGs was constructed to further explore the relationships among these genes and identify hub DEGs. Gene ontology and KEGG enrichment analyses were performed to investigate the biological role of DEGs. Besides, correlation analysis, genetic alteration, expression profile, and survival analysis of these hub DEGs were also investigated to further explore the roles of these hub gene in mechanism of EC tumorigenesis. qRT-PCR analysis was also performed to verify the expression of identified hub DEGs.

Results

A total of 40 DEGs were screened out as the DEGs with 3 upregulated and 37 downregulated in EC. The gene ontology analysis showed that these genes were significantly enriched in cell adhesion, response to estradiol, and growth factor activity, etc. The KEGG pathway analysis showed that DEGs were enriched in focal adhesion, leukocyte transendothelial migration, PI3K-Akt signaling pathway, and ECM-receptor interaction pathway. More importantly, COL1A1, IGF1, COL5A1, CXCL12, PTEN, and SPP1 were identified as the hub genes of EC. The genetic alteration analysis showed that hub genes were mainly altered in mutation and deep deletion. Expression validation by bioinformatic analysis and qRT-PCR also proved the expression of these six hub genes were differentially expressed in EC. Additionally, significantly better overall survival and disease-free survival were observed with six hub genes altered, and survival outcome in high expression of COL1A1, IGF1, and PTEN patients was also significantly better than low expression patients.

Conclusions

COL1A1, IGF1, COL5A1, CXCL12, PTEN, and SPP1 involved in the pathogenesis of EC and might be candidate genes for diagnosis of EC.
Predictive factors for pleural drainage volume after uniportal video-assisted thoracic surgery lobectomy for non-small cell lung cancer: a single-institution retrospective study
Authors: Tang Ming-bo , Li Jia-lin , Tian Su-yan , Gao Xin-liang , Liu Wei
Published: July 2020

Objective

To identify the predictive factors associated with pleural drainage volume (PDV) after uniportal video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC).

Methods

A total of 440 consecutive NSCLC patients who underwent uniportal VATS lobectomy were enrolled in this study between November 2016 and July 2019. Thirty-four parameters, including patients’ clinicopathological characteristics and other potential predictors were collected. Daily drainage volume was summed up as PDV. Univariate analysis and multivariate regression models were fitted to identify independent predictive factors for PDV.

Results

The median PDV was 840 ml during the median drainage duration of 4 days. A strong correlation was observed between PDV and drainage duration (correlation coefficient = 0.936). On univariate analysis, age, forced expiratory volume in 1 s % predicted (FEV1%), left ventricular ejection fraction (LVEF), operation time, serum total protein (TP), and body mass index (BMI) showed a significant correlation with PDV (P value, < 0.001, < 0.001, 0.003, 0.008, 0.028, and 0.045, respectively). Patients with smoking history (P = 0.030) or who underwent lower lobectomy (P = 0.015) showed significantly increased PDV than never smokers or those who underwent upper or middle lobectomy, respectively. On multivariate regression analysis, older age (P< 0.001), lower FEV1% (P< 0.001), lower LVEF (P = 0.011), lower TP (P = 0.013), and lower lobectomy (P = 0.016) were independent predictors of increased PDV.

Conclusions

Predictive factors of PDV can be identified. Based on these predictors, patients can be treated with tailored individualized safe chest tube management.
Evaluating interventions to improve test, treat, and track (T3) malaria strategy among over-the-counter medicine sellers (OTCMS) in some rural communities of Fanteakwa North district, Ghana: study protocol for a cluster randomized controlled trial
Authors: Soniran Olajoju Temidayo , Abuaku Benjamin , Ahorlu Collins Stephen
Published: July 2020

Background

The World Health Organization initiated test, treat, and track (T3) malaria strategy to support malaria-endemic countries in their efforts to achieve universal coverage with diagnostic testing, antimalarial treatment, and strengthening surveillance systems. Unfortunately, T3 is not adopted by over-the-counter medicine sellers (OTCMS) where many patients with malaria-like symptoms first seek treatment. Sub-Saharan African countries are considering introducing and scaling up RDTs in these outlets to reduce malaria burden. In this context, this study is aimed at improving implementation of the T3 among OTCMS using a number of intervention tools that could be scaled-up easily at the national level.

Methods/design

The interventions will be evaluated using a two-arm, cluster randomized trial across 8 rural communities (4 clusters per arm), in two adjacent districts (Fanteakwa North and Fanteakwa South districts) of Ghana. A total of 8 OTCMS in the intervention arm and 5 OTCMS in the control arm in the selected communities will participate in the study. In the intervention arm only, subsidized malaria rapid diagnostic test (mRDT) kits will be introduced after the OTCMS have been trained on how to use the kit appropriately. Supervision, technical assistance, feedbacks, and collection of data will be provided on a regular basis at the participating medicine stores. The primary outcome is the proportion of children under 10 years with fever or suspected to have malaria visiting OTCMS and tested (using mRDT) before treatment. Secondary outcomes will include adherence to national malaria treatment guidelines and recommended mRDT retail price. Outcomes will be measured using mainly a household survey supplemented by mystery client survey and a surveillance register on malaria tests conducted by the OTCMS during patient consultations. Data collected will be double entered and verified using Microsoft Access 2010 (Microsoft Inc., Redmond, Washington) and analyzed using STATA version 11.0.

Discussion

The trial will provide evidence on the combined effectiveness of provider and community interventions in improving adherence to the T3 initiative among OTCMS in rural Ghana.

Ethical clearance

NMIMR-IRB CPN 086/18-19

Trial registration

ISRCTN registry ISRCTN77836926. Registered on 4 November 2019.
Protocol for a randomized controlled trial to assess two procedures of vaginal native tissue repair for pelvic organ prolapse at the time of the questioning on vaginal prosthesis: the TAPP trial
Authors: Lacorre A. , Vidal F. , Campagne-Loiseau S. , Marin B. , Aubard Y. , Siegerth F. , Mesnard C. , Chantalat E. , Hocke C. , Gauthier T.
Published: July 2020

Background

Native tissue cystocele repair has been the cornerstone of prolapse surgery, especially since the learned societies warned clinicians and patients about serious mesh-related complications. Surgical techniques mainly consist in anterior colporraphy and vaginal patch plastron. However, success rates of native tissue cystocele repair are heterogeneous, depending on the design of studies and definition of outcomes. To date, high-quality data comparing vaginal native tissue procedures are still lacking.

Methods

Herein we aimed to describe the design of the first randomized controlled trial (TAPP) comparing anterior colporraphy (plication of the muscularis and adventitial layers of the vaginal wall) and vaginal patch plastron (bladder support anchored on the tendinous arch of the pelvic fascia by lateral sutures) techniques.

Our aim is to assess the effectiveness of vaginal native tissue repair at 1 year for cystocele with a combined definition of success—anatomic and functional. The primary endpoint will be the success rate 1 year after surgery with a composite of objective and subjective measures (Aa and Ba points < 0 from POP-Q (Pelvic Organ Prolapse Quantification System) and a negative answer to question 3 of Pelvic Floor Distress Inventory and no need for additional treatment).

Discussion

A prospective study has found a success rate at 35% for anterior colporraphy based on a combined definition, both anatomic and functional, as recently recommended. However, the definition of anatomic was strict (POP-Q< 2), while it seems that the best definition of anatomic success is “no prolapse among the hymen”, that is to say Aa and Ba points from the POP-Q classification < 0. We hypothesize that vaginal patch plastron will have a better anatomic and functional success comparatively to anterior colporraphy because native tissue is added, as it corrects both median and lateral cystoceles thanks to bilateral paravaginal suspension.

Trial registration

CHU LIMOGES is the sponsor of this research (n°87RI18_0013).

This research is supported by the French Department of Health (PHRC 2018-A03476-49) and will be conducted with the support of DGOS (PHRC interregional – GIRCI SOHO).

The study protocol was approved by the Human Subjects Protection Review Board (Comité de Protection des Personnes) on May 16, 2019.

The trial is registered in the ClinicalTrials.gov registry (NCT03875989).
A network-wide view-based detection and mitigation of a sophisticated Interest Flooding Attack
Authors: Cheng Guang , Zhao Lixia , Hu Xiaoyan , Zheng Shaoqi , Wu Hua , Fan Chengyu
Published: July 2020

Interest Flooding Attack (IFA) is one of the main security threats for the Named Data Networking (NDN). Most of its existing countermeasures enable intermediate routers near the attackers to independently detect the attack and consider the typical attack scenario in which attackers directly send malicious Interests at a constant and relatively high rate after the attack starts. Moreover, they may also throttle legitimate Interests when enforcing the existing defense measures at intermediate routers as it is still difficult for them to distinguish the Interests issued by attackers from those issued by legitimate consumers. Instead, this work aims at a more sophisticated attack scenario in which attackers start the attack at a relatively lower rate but gradually speed up to keep the Pending Interest Tables (PITs) of the victims increasing to finally deplete the PIT resources for legitimate consumers. It is relatively difficult for intermediate routers to independently and timely detect such a sophisticated IFA. To solve this problem, we propose a mechanism to detect and mitigate the sophisticated IFA from the network-wide view, dubbed as DMNWV. In DMNWV, a central controller monitors the network and makes a comprehensive and prompt decision on whether there is an ongoing IFA based on the overall state of the whole network collected from the abnormity information reports sent by the first-hop routers of attackers. Attack sources can be directly located after an IFA is determined, and then the routers directly connected to attackers (i.e., access routers) can take targeted measures based on the located attackers to prevent malicious Interest from entering the network without throttling legitimate Interests. We conduct an experimental study to evaluate the performance of DMNWV, explore the parameter settings of the attack detection algorithm at access routers, and measure the communication overhead of the central controller. The experimental results validate that DMNWV can timely detect and mitigate the sophisticated IFA without throttling requests from legitimate consumers with significantly low communication overhead of the central controller, which will not bring about too much burden to the network.
Exponential mean-square stability of numerical solutions for stochastic delay integro-differential equations with Poisson jump
Authors: Ahmadian Davood , Farkhondeh Rouz Omid
Published: July 2020

In this paper, we investigate the exponential mean-square stability for both the solution of n-dimensional stochastic delay integro-differential equations (SDIDEs) with Poisson jump, as well for the split-step θ-Milstein (SSTM) scheme implemented of the proposed model. First, by virtue of Lyapunov function and continuous semi-martingale convergence theorem, we prove that the considered model has the property of exponential mean-square stability. Moreover, it is shown that the SSTM scheme can inherit the exponential mean-square stability by using the delayed difference inequality established in the paper. Eventually, three numerical examples are provided to show the effectiveness of the theoretical results.
The controllability of damped fractional differential system with impulses and state delay
Authors: Nawaz Musarrat , Wei Jiang , Sheng Jiale , Khan Azmat Ullaha
Published: July 2020

We discuss the controllability for a damped fractional differential system with impulses and state delay, which involves Caputo fractional derivatives. Deriving the condition based on the Gramian matrix defined by the Mittag-Leffler matrix function and Laplace transformation, we establish necessary and sufficient conditions of controllability criteria. Finally, we construct two numerical examples to support the result.
Theoretical analysis of the delay on the p53 micronetwork
Authors: Wang Danni , Liu Nan , Yang Hongli , Yang Liangui
Published: July 2020

Time delay plays a crucial role in p53 dynamic. However, the theoretical understanding is still lower. Thus we construct a micro-differential equation model and introduce the time delay τ based on the regulation process. Firstly, we linearize the system and analyze the associated characteristic equation. We can conclude that there exists the delay threshold $\tau _{0}$

τ
0

such that when the delay τ is less than $\tau _{0}$

τ
0

, the system is asymptotically stable and otherwise stable oscillations occur. Secondly, we use the normal form method and the center manifold theorem to derive the direction and stability of the Hopf bifurcation. Finally, by numerical simulations we verify our theoretical results. We also find that the effect of noise on the amplitude is more severe than that of the period, which well agrees with the experimental results.
High level MYCN amplification and distinct methylation signature define an aggressive subtype of spinal cord ependymoma
Authors: Raffeld Mark , Abdullaev Zied , Pack Svetlana D. , Xi Liqiang , Nagaraj Sushma , Briceno Nicole , Vera Elizabeth , Pittaluga Stefania , Lopes Abath Neto Osorio , Quezado Martha , Aldape Kenneth , Armstrong Terri S. , Gilbert Mark R.
Published: July 2020

We report a novel group of clinically aggressive spinal cord ependymomas characterized by Grade III histology, MYCN amplification, an absence of NF2 alterations or other recurrent pathogenic mutations, and a unique methylation classifier profile. Seven cases were found to have MYCN amplification in the course of routine mutational profiling of 552 patients with central nervous system tumors between December 2016 and July of 2019 and an eighth patient was identified from an unrelated set of cases. Methylation array analysis revealed that none of the 8 cases clustered with any of the nine previously described ependymoma methylation subgroups, and 7 of 8 formed their own tight unique cluster. Histologically all cases showed grade III features, and all demonstrated aggressive clinical behavior. These findings are presented in the context of data from three other studies describing similar cases. Therefore, a combined total of 27 MYCN amplified spinal cord ependymoma cases have now been reported in the literature, warranting their consideration as a distinctive subtype of spinal cord ependymoma (SP-EPN-MYCN) with their unique molecular characteristics and aggressive clinical behavior.
Erythrocytic α-synuclein contained in microvesicles regulates astrocytic glutamate homeostasis: a new perspective on Parkinson’s disease pathogenesis
Authors: Sheng Lifu , Stewart Tessandra , Yang Dishun , Thorland Eric , Soltys David , Aro Patrick , Khrisat Tarek , Xie Zhiying , Li Na , Liu Zongran , Tian Chen , Bercow Matthew , Matsumoto Junichi , Zabetian Cyrus P. , Peskind Elaine , Quinn Joseph F. , Shi Min , Zhang Jing
Published: July 2020

Parkinson’s disease is a neurodegenerative disorder characterized by the transmission and accumulation of toxic species of α-synuclein (α-syn). Extracellular vesicles (EVs) are believed to play a vital role in the spread of toxic α-syn species. Recently, peripheral α-syn pathology has been investigated, but little attention has been devoted to erythrocytes, which contain abundant α-syn. In this study, we first demonstrated that erythrocyte-derived EVs isolated from Parkinson’s disease patients carried elevated levels of oligomeric α-syn, compared to those from healthy controls. Moreover, human erythrocyte-derived EVs, when injected into peripheral blood in a mouse model of Parkinson’s disease, were found to readily cross the blood-brain barrier (BBB). These EVs accumulated in astrocyte endfeet, a component of the BBB, where they impaired glutamate uptake, likely via interaction between excitatory amino acid transporter 2 (EAAT2) and oligomeric α-syn. These data suggest that erythrocyte-derived EVs and the oligomeric α-syn carried in them may play critical roles in the progression or even initiation of Parkinson’s disease. Additionally, the mechanisms involved are attributable at least in part to dysfunction of astrocytes induced by these EVs. These observations provide new insight into the understanding of the mechanisms involved in Parkinson’s disease.
Comment on “volume-outcome relationship on survival and cost benefits in severe burn injury: a retrospective analysis of a Japanese nationwide administrative database” (Endo et al., Journal of Intensive Care 2019)
Authors: Osuka Akinori , Miyao Daiki , Kuroki Yuichi
Published: July 2020

This is a critical comment on the paper by Endo et al. on the volume-outcome relationship on survival and cost benefits in severe burn injury which addresses biases related to patient transfer and burn severity assessment.
Gluteal-fold flap repair of rectovaginal fistula caused by aluminum potassium sulfate hydrate-tannic acid injection for internal hemorrhoids: a case report
Authors: Yoshimitsu Masanori , Egi Hiroyuki , Nagamatsu Shogo , Shimomura Manabu , Hakoda Keishi , Miguchi Masashi , Kohashi Toshihiko , Okajima Masazumi , Ohdan Hideki
Published: July 2020

Background

Rectovaginal fistula (RVF) following aluminum potassium sulfate hydrate-tannic acid (ALTA) injection therapy for hemorrhoids is a rare complication. We report the first case of RVF after ALTA injection therapy successfully treated by gluteal-fold flap.

Case presentation

A 49-year-old female suffered from a fever and rectal ulcer after undergoing internal hemorrhoid treatment with a submucosal ALTA injection at a previous clinic. One week after ALTA therapy, she noted obvious passage of flatus and stool through the vagina, and was diagnosed with RVF by anoscope at another clinic. She was referred to our hospital 3 weeks after ALTA therapy. Sigmoid colostomy was performed for fecal diversion as a preliminary step for fistula repair. However, the fistula was scarred and the defect between the rectum and vagina did not improve at all. Ten months after ALTA therapy, we performed fistula repair by gluteal-fold flap. Seven months later, sigmoid-colostomy reversal was performed. The patient has experienced no RVF in the 3 years since sigmoid-colostomy reversal.

Conclusions

The gluteal-fold flap strategy is a useful option for severe RVF management.
New findings useful for clinical practice using swept-source optical coherence tomography angiography in the follow-up of active ocular toxoplasmosis
Authors: de Oliveira Dias João Rafael , Campelo Camila , Novais Eduardo Amorim , de Andrade Gabriel Costa , Marinho Paula , Zamora Yusláy Fernández , Peixoto Luciana Finamor , Maia Maurício , Nascimento Heloísa , Belfort Rubens
Published: July 2020

Background

Ocular toxoplasmosis is one of the most common causes of intraocular inflammation and posterior uveitis in immunocompetent patients. This paper aims to investigate swept-source optical coherence tomography angiography (SS-OCTA) findings in eyes with active toxoplasmic retinochoroiditis.

Methods

This case series was conducted from November 2017 through October 2019 in two Brazilian centers. 15 eyes of 15 patients with active toxoplasmic retinochoroiditis were included, and were imaged at baseline and after at least 4 weeks of follow-up. All patients underwent ophthalmic examinations and multimodal imaging including SS-OCT and SS-OCTA before and after treatment of ocular toxoplasmosis. The differential diagnoses included toxoplasmosis, syphilis, and human immunodeficiency virus, which were eliminated through serologic and clinical evaluations.

Results

All 15 patients presented with positive anti-Toxoplasma gondii immunoglobulin G titers and three also presented with positive anti-T. gondii immunoglobulin M titers. The mean age at examination was 32.4 years ± 12.7 years (range 15–59 years). Sixty percent of the patients were female. In all eyes, the inner retinal layers were abnormally hyperreflective with full-thickness disorganization of the retinal reflective layers at the site of the active toxoplasmic retinochoroiditis. At baseline, 80% of eyes had focal choroidal thickening beneath the retinitis area, and all eyes had a choroidal hyporeflective signal. Before treatment, SS-OCTA showed no OCTA decorrelation signal next to the lesion site in all eyes, and flow signal improvement was noticed after treatment. Three eyes presented with intraretinal vascular abnormalities during follow-up. SS-OCTA showed retinal neovascularization in one patient and a presumed subclinical choroidal neovascular membrane in another patient.

Conclusions

SS-OCT and SS-OCTA are useful for assessing unexpected structural and vascular retinal and choroidal changes in active and post-treatment toxoplasmic retinochoroiditis and these findings are useful for clinical practice.
Failure prediction using personalized models and an application to heart failure prediction
Authors: Roy Asim , Bruce Charles , Schulte Phillip , Olson Lyle , Pola Manasa
Published: July 2020

Background

To reduce disruptions of processes and the cost of maintenance, predicting the onset of failure (or a similar event) of a physical system (or components of a physical system) has become important. Prediction of onset of failure would allow appropriate corrective actions at the right time. In this paper, we present a method to predict the “onset” of failure (the start of a degradation process or similar types of events) of a physical system that minimizes data collection and personalizes it for the physical system. The method applies to situations where one monitors the operating characteristics of the physical system at regular time intervals by means of attached sensors and other measurement instruments. It creates a model of the physical system, during normal operations, using the time-series data produced by the sensors and measurement instruments. However, it does not create or use any time-series models. It simply examines the distribution of time-series data across different time periods. It uses this model of normal operations in subsequent time periods to monitor the physical system for deviations from normality.

Results

We illustrate this method with an application to predict the “onset” of subsequent decompensated heart failures for patients already treated for a heart failure at a hospital. As part of an NIH study, these heart failure patients received two ECG patches, an accelerometer and a bio-impedance measurement device for regular monitoring for a period after their release from the hospital.

Conclusions

When dealing with non-homogenous, disparate physical systems, personalized models can be better predictors of a phenomenon compared to generalized models based on data collected from an assortment of such physical systems. In medicine such models can be a powerful addition to the set of medical diagnostic tools. And such personalized models can be built rather quickly without waiting for extensive data collection.
Virtual experimental platforms in chemistry laboratory education and its impact on experimental self-efficacy
Authors: Kolil Vysakh Kani , Muthupalani Sharanya , Achuthan Krishnashree
Published: July 2020

Self-efficacy is an important determinant in successfully attempting a task. In the area of education, self-efficacy plays a crucial role in causing behavioral changes, resulting in enhanced performance over the course of learning. In chemistry education, students often develop anxiety towards performing experiments due to the perceived negative outcomes resulting from lack of understanding and improper experimentation. This anxiety negatively impacts the self-efficacy of students in performing laboratory experiments. We define student-held beliefs about their experimental skills as ’experimental self-efficacy’ (ESE), and examine the four prominent factors that impact ESE in chemical laboratories. Through the development of an instrument, this work characterizes ESE and the impact of pre-laboratory interventions such as exposure to virtual laboratories (VL) on ESE and conceptual knowledge of students. Furthermore, analysis using statistical techniques such as t-tests and dissimilarity matrices reveal the positive impact of VL in enhancing students’ ESE.
Harnessing repeated measurements of predictor variables for clinical risk prediction: a review of existing methods
Authors: Bull Lucy M. , Lunt Mark , Martin Glen P. , Hyrich Kimme , Sergeant Jamie C.
Published: July 2020

Background

Clinical prediction models (CPMs) predict the risk of health outcomes for individual patients. The majority of existing CPMs only harness cross-sectional patient information. Incorporating repeated measurements, such as those stored in electronic health records, into CPMs may provide an opportunity to enhance their performance. However, the number and complexity of methodological approaches available could make it difficult for researchers to explore this opportunity. Our objective was to review the literature and summarise existing approaches for harnessing repeated measurements of predictor variables in CPMs, primarily to make this field more accessible for applied researchers.

Methods

MEDLINE, Embase and Web of Science were searched for articles reporting the development of a multivariable CPM for individual-level prediction of future binary or time-to-event outcomes and modelling repeated measurements of at least one predictor. Information was extracted on the following: the methodology used, its specific aim, reported advantages and limitations, and software available to apply the method.

Results

The search revealed 217 relevant articles. Seven methodological frameworks were identified: time-dependent covariate modelling, generalised estimating equations, landmark analysis, two-stage modelling, joint-modelling, trajectory classification and machine learning. Each of these frameworks satisfies at least one of three aims: to better represent the predictor-outcome relationship over time, to infer a covariate value at a pre-specified time and to account for the effect of covariate change.

Conclusions

The applicability of identified methods depends on the motivation for including longitudinal information and the method’s compatibility with the clinical context and available patient data, for both model development and risk estimation in practice.
Development of an electronic patient-reported outcome measure (ePROM) system to aid the management of patients with advanced chronic kidney disease
Authors: Kyte Derek , Anderson Nicola , Auti Ram , Aiyegbusi Olalekan Lee , Bishop Jon , Bissell Andrew , Brettell Elizabeth , Calvert Melanie , Chadburn Marie , Cockwell Paul , Dutton Mary , Eddington Helen , Forster Elliot , Hadley Gabby , Ives Natalie J. , Jackson Louise , O’Brien Sonja , Price Gary , Sharpe Keeley , Stringer Stephanie , Stephenson Gael , Verdi Rav , Waters Judi , Wilcockson Adrian , Williams Jim
Published: July 2020

Background

Effective management of patients with chronic kidney disease (CKD) relies on timely detection of clinical deterioration towards end stage kidney failure. We aimed to design an electronic Patient-Reported Outcome Measure (ePROM) system, which would allow patients with advanced CKD (pre-dialysis) to: (i) remotely self-report their symptoms using a simple and secure online platform; (ii) share the data with the clinical team in real-time via the electronic patient record to help optimise care. We adopted a staged development process which included: a systematic review of PROMs used in CKD; formation of a co-design team; prototype system design/development, user acceptance testing and refinement; finalisation of the system for testing in a pilot/feasibility trial.

Results

A co-design team was convened, including patients with lived experience of CKD; clinical team members; IT/Informatics experts; academics; and Birmingham Clinical Trials Unit representatives. A prototype system was developed and iterative changes made before finalisation during a series of operational meetings. The system allows patients to remotely self-report their symptoms; provides tailored self-management advice; allows monitoring of real-time patient ePROM data; sends automated notifications to the patient/clinical team in the advent of a severe symptom report; and incorporates longitudinal ePROM symptom data into the electronic patient record. Feasibility of the system will be evaluated as part of the National Institute for Health Research funded RePROM (Renal electronic Patient-Reported Outcome Measure) pilot trial (ISRCTN12669006).

Conclusions

Routine ePROM collection with real-time feedback has the potential to improve outcomes and reduce health service costs. We have successfully developed a trial-ready ePROM system for advanced CKD, the feasibility of which is currently being explored in a pilot trial. Assuming feasibility is demonstrated, formal evaluation of efficacy will take place in a future multi-centre randomised controlled trial.
Isolation of indigenous strains of the white halo fungus as a biological control agent against 3rd instar larvae of tobacco caterpillar, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae)
Authors: Dhanapal R. , Kumar D. V. Sai Ram , Lakshmipathy R. , Rani C. Sandhya , Kumar V. Manoj
Published: July 2020

The farmer interest in biological control-based management practices using entomopathogenic fungi (EPF) for the control of many economically important insects has increased. In this process, selection of effective strains of EPF is an important criterion to control the target insect pests in efficient manner. In this context, this research work was formulated to find out environmentally effective strains of EPF in the soils of costal districts of Andhra Pradesh, India. Out of 135 soil samples collected, 9 yielded 9 strains of Lecanicillium lecanii. Among all 9 L. lecanii isolates, the least median lethal concentration (LC50) for 3rd instar larvae of the tobacco caterpillar, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae), was 1.17 × 106 spores ml−1 in L-8, followed by 1.27 × 106 spores ml−1 in L-5 in an increasing order. Likewise, the median lethal time (LT50) values of different isolates of EPF against the 3rd instar of S. litura were calculated for the uniform highest concentration of 1 × 108 spores ml−1. Among all 9 L. lecanii isolates, the lowest median lethal time (LT50) was observed as 7.70 days by L-8, followed by 7.77 days by L-5 and 8.50 days by L-7.