bluuebunny/crossref_metadata_2025 huggingface dataset:
Positive intervention for depression and teacher–student relationship in Iranian high school girl students with moderate/mild depression: a pilot randomized controlled trial
Authors: Taghvaienia Ali , Zonobitabar Arash
Published: June 2020

Background

Positive intervention (PI) is a modern and therapeutic approach broadly based on the principles of positive psychology (Rashid in J Posit Psychol 1:25–40, 2014). PI effects at schools have received little attention to date. However, since PI offers a focus on the positive aspects of human experience (Seligman and Csikszentmihalyi in Am Psychol 55:5–14, 2000), we hypothesized that it could exert positive changes in the teacher-student relationship (TSR) and depression symptoms. Therefore, the mentioned pilot study conducted in this article aimed at evaluating PI effects on depression and TSR among Iranian high school girl students with moderate/mild depression.

Method

In this research, 60 eligible female students (aged 15–18) with a Beck Depression Inventory-II (BDI-II) mild-moderate depression diagnosis, were randomly divided into PI (n = 30) and control groups (n = 30) at the time of entering the study and 2 months later following their assessments through the Inventory of TSR (IT-SR) and BDI-II. The intervention group participated in 8-week 2 h group sessions of PI and the control group was evaluated without any intervention.

Results

The study was completed with a total number of 49 girls [PI group (n = 24), and control group (n = 25)] and everybody participate in 8 sessions. The intervention group was effective on the variables of BDI-II and IT-SR in a way that the involved girls increased their communication (p = 0.001,d = 0.17), trust (p = 0.001d = 0.14) after PI training and decreased alienation (p = 0.012,d = 0.11) and depression (p = 0.001,d = 0.15) among other high school students.

Conclusion

This intervention could function as an unspecific component of a stepped care approach for teenage girls suffering from depression. This study recommends more RCT with large sample sizes among high school boys students and follow-up.
Health care professionals’ perspectives on barriers to treatment seeking for formal health services among orphan children and adolescents with HIV/AIDS and mental distress in a rural district in central, Uganda
Authors: Mugisha James , Kinyanda Eugene , Osafo Joseph , Nalukenge Winfred , Knizek Birthe Loa
Published: June 2020

Background

Little/no research has been conducted in Uganda in particular and sub-Saharan Africa in general on the health professional’s perspectives on barriers to treatment seeking for formal health services among orphan children and adolescents with a double burden of HIV/AIDS and mental distress.

Aim

To explore health professionals’ perspectives on barriers to treatment seeking for formal health services among orphan children and adolescents with HIV/AIDS and mental distress in Masaka, Uganda.

Method

Qualitative research design using key informant interviews with health service managers and staff in agencies working with children and adolescents with HIV/AIDS in Masaka district, Uganda.

Results

Barriers to treatment seeking reported by health care professionals were quite enormous and are summarized under: family, individual, community and health systems level barriers. The crosscutting finding here is that the societal informal and formal systems of care had been affected by the HIV/AIDs epidemic, and, mental distress aggravates this challenge for the individuals afflicted and families affected by mental distress.

Conclusion

Children and adolescents with both HIV/AIDS and mental distress are vulnerable due to constraints at family, community and health systems levels. Effective public health interventions to address the double burden of HIV/AIDS and mental distress will be vital in the study communities addressing the constraints at family, community and institutional level. Public health interventions should aim at increased access and effective utilization of services for both HIV/AIDS and mental health services. Stigma reduction strategies at individual, family and community levels are also recommended.
Propionic acid induces dendritic spine loss by MAPK/ERK signaling and dysregulation of autophagic flux
Authors: Choi Hyosun , Kim In Sik , Mun Ji Young
Published: June 2020

Propionic acid (PPA) is a short-chain fatty acid that is an important mediator of cellular metabolism. It is also a by-product of human gut enterobacteria and a common food preservative. A recent study found that rats administered with PPA showed autistic-like behaviors like restricted interest, impaired social behavior, and impaired reversal in a T-maze task. This study aimed to identify a link between PPA and autism phenotypes facilitated by signaling mechanisms in hippocampal neurons. Findings indicated autism-like pathogenesis associated with reduced dendritic spines in PPA-treated hippocampal neurons. To uncover the mechanisms underlying this loss, we evaluated autophagic flux, a functional readout of autophagy, using relevant biomedical markers. Results indicated that autophagic flux is impaired in PPA-treated hippocampal neurons. At a molecular level, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway was activated and autophagic activity was impaired. We also observed that a MAPK inhibitor rescued dendritic spine loss in PPA-treated hippocampal neurons. Taken together, these results suggest a previously unknown link between PPA and autophagy in spine formation regulation in hippocampal neurons via MAPK/ERK signaling. Our results indicate that MAPK/ERK signaling participates in autism pathogenesis by autophagy disruption affecting dendritic spine density. This study may help to elucidate other mechanisms underlying autism and provide a potential strategy for treating ASD-associated pathology.
Transcription activation of circ-STAT3 induced by Gli2 promotes the progression of hepatoblastoma via acting as a sponge for miR-29a/b/c-3p to upregulate STAT3/Gli2
Authors: Liu Yanfeng , Song Jianping , Liu Yu , Zhou Zhipeng , Wang Xianqiang
Published: June 2020

Background

Hepatoblastoma (HB) is a common liver malignancy in children. Our previous study has disclosed the crucial role of STAT3 (signal transducer and activator of transcription 3) in HB.

Aim of the study

Present study was designed to study the circular RNA (circRNA) STAT3 in HB.

Methods

Gel electrophoresis revealed the circular characteristics of circ-STAT3. Function assays like EdU, transwell and sphere formation assay disclosed the function of circ-STAT3 in HB cells. Mechanism assays including ChIP, RIP, RNA pull down assay demonstrated the macular mechanism underlying circ-STAT3.

Results

Circ_0043800, which was originated from STAT3, was up-regulated in HB tissues and cells. More importantly, silencing of circ-STAT3 led to the inhibition on HB cell growth, migration and stem-cell characteristics. Circ_0043800 was predominantly located in the cytoplasm of HB cells. Then, circ_0043800 was found to up-regulate STAT3 via sponging miR-29a/b/c-3p. Besides, we identified that STAT3 overexpression partially rescued silenced circ_0043800, while miR-29a/b/c-3p inhibition completely rescued silenced circ_0043800 on HB cellular biological behaviors. Subsequently, Gli2 (GLI family zinc finger 2) was identified as another target of miR-29a/b/c-3p. Circ_0043800 served as a competing endogenous RNA (ceRNA) to up-regulate both Gli2 and STAT3 via sponging miR-29a/b/c-3p. Moreover, we figured out that Gli2 overexpression completely rescued silenced circ_0043800 on HB cell malignant behaviors. After that, we discovered that Gli2 transcriptionally activated circ_0043800. The in-vivo assays further revealed that circ_0043800 promoted HB tumor growth by up-regulation of Gli2 and STAT3.

Conclusion

Gli2-induced circ_0043800 served as the ceRNA to promote HB by up-regulation of STAT3 and Gli2 at a miR-29a/b/c-3p dependent manner.
PKM2 inhibition may reverse therapeutic resistance to transarterial chemoembolization in hepatocellular carcinoma
Authors: Martin Sean P. , Fako Valerie , Dang Hien , Dominguez Dana A. , Khatib Subreen , Ma Lichun , Wang Haiyang , Zheng Wei , Wang Xin Wei
Published: June 2020

Background

Therapeutic options for patients with hepatocellular carcinoma (HCC) are limited. Transarterial chemoembolization (TACE) is an interventional procedure used to deliver chemotherapy and embolizing agents directly to the tumor and is the procedure of choice for patients with intermediate stage HCC. While effective, more than 40% of patients do not respond to therapy, highlighting the need to investigate possible mechanisms of resistance. We sought to evaluate mechanisms of TACE resistance and evaluate a potential therapeutic target to overcome this resistance.

Methods

Using a prognostic gene signature which predicts TACE response (TACE Navigator) in a cohort of HCC patients who received TACE, patients were classified as responders and non-responders. Transcriptomic and gene pathway analysis were used to identify potential drivers of TACE resistance. Knockdown of the gene encoding rate limiting enzyme PKM2 using shRNA in HCC cell lines, as well as pharmacologic inhibition of PKM2 with shikonin using an in vitro TACE model measured response to chemotherapy under hypoxia. Finally, we replicated the TACE model with shikonin using patient derived cell line organoids (PDC). Functional studies were performed in vitro using immunoblotting, quantitative polymerase chain reaction, glycolysis and hypoxia assays.

Results

In patient non-responders, we identified enrichment of the glycolysis pathway, specifically of the gene encoding the rate-limiting enzyme PKM2. We identified four HCC cell lines which recapitulated a TACE responder-like and non-responder-like phenotype. PKM2 knockdown in HCC cell lines demonstrated a less proliferative and aggressive phenotype as well as improved drug sensitivity to both doxorubicin and cisplatin. In vitro TACE model demonstrated that TACE non-responder-like cells overcame therapeutic resistance and rendered them susceptible to therapy through PKM2 knockdown. Lastly, we obtained similar results using a pharmacologic PKM2 inhibitor, shikonin in both cell lines, and PDC organoids.

Conclusion

Elevated PKM2 is associated with treatment resistance and abbreviated survival in patients receiving TACE. Elevated PKM2 in vitro is associated with increased utilization of the glycolysis pathway, resulting in oxygen independent cell metabolism. Through PKM2 knockdown as well as with pharmacologic inhibition with shikonin, non-responder cells can be reprogrammed to act as responders and could improve TACE efficacy in patients.
Impact of fecal microbiota transplantation on chronic recurrent pouchitis in ulcerative colitis with ileo-anal anastomosis: study protocol for a prospective, multicenter, double-blind, randomized, controlled trial
Authors: Trang-Poisson Caroline , Kerdreux Elise , Poinas Alexandra , Planche Lucie , Sokol Harry , Bemer Pascale , Cabanas Karine , Hivernaud Eliane , Biron Laetitia , Flet Laurent , Montassier Emmanuel , Le Garcasson Ghislaine , Chiffoleau Anne , Jobert Alexandra , Lepelletier Didier , Caillon Jocelyne , Le Pape Patrice , Imbert Berthe-Marie , Bourreille Arnaud
Published: June 2020

Background

Almost 15% of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch–anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available.

Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UC-associated pouchitis. However, there is currently no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis.

Methods

Our project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation.

Discussion

On April 30, 2014, the World Health Organization published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future.

Trial registration

ClinicalTrials.gov, NCT03524352. Registered on 14 May 2018.
The Stop-Tabac smartphone application for smoking cessation: study protocol for a randomized controlled trial in the general population
Authors: Etter Jean-François , Khazaal Yasser
Published: June 2020

Background

Smartphone-based support can reach thousands of smokers and help those who would otherwise try to quit smoking by themselves with little chance of success. Nicotine medications double the chances of quitting smoking, but few smokers use them, and they often use them for too short a time and at an insufficient dose. It is therefore important to increase access to support for smoking cessation and compliance with nicotine therapy. The objectives of this study are to assess whether the Stop-Tabac application (app) is effective for smoking cessation and to examine whether the outcome is influenced by the personal characteristics of participants.

Methods

Trial design: this is a two-arm, parallel-group, superiority, individually randomized, “placebo” controlled trial in 5200 smokers, with follow up after 1 week, 1 month and 6 months. The participants are adult daily smokers (N = 5200) enrolled on the Internet, living in France or Switzerland. The intervention is the Stop-tabac fully-automated app for smartphones, which was launched in 2012 and continuously improved thereafter. It includes fact sheets; calculators of cigarettes not smoked, money saved, and years of life gained; an interactive “coach” that provides automated, individually tailored counseling messages based on the user’s personal profile, sent regularly for 6 months; immediate feedback during episodes of craving and tobacco withdrawal symptoms; a discussion forum (“The Tribe”) where participants provide and receive social support; a quiz that informs users in a playful way; and a module on nicotine therapy that includes personalized feedback and follow up. The outcome is self-reported smoking cessation after 6 months (no puff of tobacco in the past 4 weeks), and after 1 week and 1 month (no puff in the past 7 days). Participants will be randomized automatically based on a list of random numbers. Participants, assistants in charge of collecting follow-up data and data analysts will be blinded to allocation. Funding is provided by the Swiss National Science Foundation, CHF 194,942 (EUR 182,200, USD 200,700), grant 32003_179369. JFE’s salary is paid by the University of Geneva, YK’s salary is paid by the Lausanne University Hospitals.

Discussion

There is little evidence from randomized trials of the impact of health apps in general and of smoking cessation apps in particular. This study will fill this gap.

Trial registration

ISRCTN Registry: ISRCTN11318024. Registered on 17 May 2018.
CASS (CyanoAcrylate closure versus Surgical Stripping for incompetent saphenous veins) study: a randomized controlled trial comparing clinical outcomes after cyanoacrylate closure and surgical stripping for the treatment of incompetent saphenous veins
Authors: Cho Sungsin , Park Hyung Sub , Lee Taeseung , Byun Seung Jae , Yun Woo-Sung , Yang Shin-Seok , Kim Hyangkyoung , Kim Woo-Shik , Joh Jin Hyun , Jung In Mok
Published: June 2020

Background

Several modalities are used for the treatment of varicose veins. Open surgical treatment with ligation and stripping of the saphenous vein has been the standard of care for many years. Endovenous thermal ablation has been shown to be a safe and effective alternative with high, long-term, target-vein closure rates. Despite this, there is the possibility of thermal injury to surrounding structures. The recently introduced cyanoacrylate closure is also considered to be a good alternative and the risk of injury to surrounding structures is minimal. The purpose of this study is to demonstrate the non-inferiority of cyanoacrylate closure with the VenaSeal™ closure system compared to surgical stripping in terms of clinical outcomes for the treatment of incompetent great saphenous veins.

Methods/design

This is an open-label, multicenter, prospective, randomized controlled trial evaluating the non-inferior clinical outcomes of cyanoacrylate closure compared to surgical stripping for the treatment of incompetent saphenous veins. After baseline measurements, participants will be randomly allocated into either the cyanoacrylate closure group or the surgical-stripping group. The primary endpoint of the study is the complete closure rate of the target vein in the cyanoacrylate closure group, and the absence of venous reflux or residual venous tissue after surgical stripping in the surgical-stripping group. These endpoints will be measured by Doppler ultrasound performed by qualified vascular technologists or investigators at 3 months after treatment. Secondary outcomes include perioperative pain, postoperative ecchymosis, clinical assessment (including general and disease-specific quality of life evaluations), complete closure rate, and absence of venous reflux or residual venous tissue at the 12- and 24-month follow-ups, as well as all adverse event rates during the 24-month follow-up period.

Discussion

This multicenter randomized controlled trial is designed to show non-inferiority in terms of complete closure rate of cyanoacrylate compared to surgical stripping for the treatment of incompetent saphenous veins.

Trial registration

Clinical Research Information Service (CRIS), ID: KCT0003203. Registered on 20 September 2018.
A techno-practical method for overcoming the biotoxicity and volatility obstacles of butanol and butyric acid during whole-cell catalysis by Gluconobacter oxydans
Authors: Hua Xia , Du GenLai , Zhou Xin , Nawaz Ali , ul Haq Ikram , Xu Yong
Published: June 2020

Background

Butyric acid is a platform chemical material, the production of which has been greatly stimulated by the diverse range of downstream applications in many industries. In particular, higher quality butyric acid used in food and medicine, is more dependent on microbiological production methods. Hence, the bio-oxidation of butanol to butyric acid has been identified as a promising method with good potential economic and environmental benefits. However, both butanol and butyric acid are usually intensively toxic to most microorganisms as well as the bio-oxidation pathway. To develop a green, efficient and competitive microbiological method is the primary work to overcome the bottleneck of butyric acid industry.

Result

A combined bioprocess was designed with alternative whole-cell catalysis for butyric acid bio-conversion from butanol by Gluconobacter oxydans in a sealed-oxygen supply bioreactor (SOS). In the operation system, the escape of volatile substrates and toxic chemicals to cells can be avoided by the use of a sealed bioreactor, combined with the rejuvenation of cells by supplying energy co-factors. Finally, during a one-batch whole-cell catalysis, the utilization rate of substrate increased from 56.6 to 96.0% by the simple skill. Additionally, the techno-practical bioprocess can realize the purpose of cell-recycling technology through the rejuvenation effect of co-factor. Finally, we obtained 135.3 g/L butyric acid and 216.7 g/L sorbose during a 60-h whole-cell catalysis. This techno-practical technology provides a promising approach to promote the industrial production of butyric acid with more competitiveness.

Conclusion

The techno-practical biotechnology has powerfully promoted the process of butyric acid production by microorganisms, especially makes up for the lack of aerobic fermentation in the industry, and surmounts the shortcomings of traditional anaerobic fermentation. At the same time, this technically practical system provides a promising approach for the promotion of the industrial production of butyric acid in a more competitive manner.
First record of besnoitiosis caused by Besnoitia bennetti in donkeys from the UK
Authors: Elsheikha Hany M. , Schares Gereon , Paraschou Georgios , Sullivan Rebekah , Fox Richard
Published: June 2020

Background

The involvement of Besnoitia bennetti in skin pathologies was investigated in a series of 20 donkeys from the Donkey Sanctuary in England, in the 2013–2019 period.

Methods

The initial histopathological finding of Besnoitia cysts in skin lumps that were presumed to be sarcoids in 2013 triggered our cognisance of this parasite and resulted in identification of a total of 20 cases. Histopathological examination of surgical biopsy samples collected from 8 live donkeys and tissue specimens from 12 deceased donkeys at post-mortem examination revealed the presence of Besnoitia cysts in all 20 donkeys. The indirect fluorescent antibody test (IFAT) and immunoblotting analysis showed the presence of anti-Besnoitia antibodies in archived serum samples from 4 deceased donkeys. Additionally, infection was evidenced in one live donkey based on IFAT and immunoblot analysis of tissue fluid of a dermal mass containing Besnoitia cysts, and real-time (RT)-PCR analysis and microsatellite genotyping of DNA isolated from the tissue of the same dermal mass confirmed the infection specifically as B. bennetti.

Results

Both serological and microsatellite analyses confirmed the aetiology to be B. bennetti. Our findings suggested that in cases of skin masses such as sarcoids, the suspicion of B. bennetti infection should be borne in mind even when clinical and histopathology examination results are negative in order to avoid misdiagnosis.

Conclusions

This case series documents, to our knowledge, the first report of B. bennetti infection in donkeys in the UK, indicating that donkey besnoitiosis has become noteworthy in the UK. Further investigations of the occurrence, epidemiological characteristics, and clinical manifestations of B. bennetti infection in donkeys and other equids are warranted.
The egg and larval pheromone dodecanoic acid mediates density-dependent oviposition of Phlebotomus papatasi
Authors: Kowacich Dannielle , Hatano Eduardo , Schal Coby , Ponnusamy Loganathan , Apperson Charles S. , Shymanovich Tatsiana , Wasserberg Gideon
Published: June 2020

Background

Gravid females assess the conditions of oviposition sites to secure the growth and survival of their offspring. Conspecific-occupied sites may signal suitable oviposition sites but may also impose risk due to competition or cannibalism at high population density or heterogeneous larval stage structure, respectively. Chemicals in the habitat, including chemicals emitted from other organisms, serve as cues for females to assess habitat conditions. Here, we investigated the attraction and oviposition preference of the Old World cutaneous leishmaniasis vector, Phlebotomus papatasi, to young and old conspecific stages, including eggs and evaluated the effect of a semiochemical associated with eggs and neonate larvae.

Methods

Attraction and oviposition preference of Ph. papatasi to each of various life stages (eggs, first-, second-, third-, fourth-instar larvae, pupae and male and female adults) was investigated using cage and oviposition jar behavioral assays. Identification of organic chemical compounds extracted from eggs was performed using GC-MS and chemicals were tested in the same behavioral assays in a dose-response manner. Behavioral responses were statistically analyzed using logistic models.

Results

Gravid Ph. papatasi females were significantly attracted to and preferred to oviposit on medium containing young life stages (eggs and first instars). This preference decreased towards older life stages. Dose effect of eggs indicated a hump-shaped response with respect to attraction but a concave-up pattern with respect to oviposition. Chemical analysis of semiochemicals from eggs and first-instar larvae revealed the presence of dodecanoic acid (DA) and isovaleric acid. Sand flies were attracted to and laid more eggs at the lowest DA dose tested followed by a negative dose-response.

Conclusions

Findings corroborated our hypothesis that gravid sand flies should prefer early colonized oviposition sites as indicators of site suitability but avoid sites containing older stages as indicators of potential competition. Findings also supported the predictions of our hump-shaped oviposition regulation (HSR) model, with attraction to conspecific eggs at low-medium densities and switching to repellence at high egg densities. This oviposition behavior is mediated by DA that was identified from surface extracts of both eggs and first-instar larvae. Isovaleric acid was also found in extracts of both stages.
Nocturnal blood pressure dipping as a marker of endothelial function and subclinical atherosclerosis in pediatric-onset systemic lupus erythematosus
Authors: Chang Joyce C. , Xiao Rui , Meyers Kevin E. , Mercer-Rosa Laura , Natarajan Shobha S. , Weiss Pamela F. , Knight Andrea M.
Published: June 2020

Background

Loss of the normal nocturnal decline in blood pressure (BP), known as non-dipping, is a potential measure of cardiovascular risk identified by ambulatory blood pressure monitoring (ABPM). We sought to determine whether non-dipping is a useful marker of abnormal vascular function and subclinical atherosclerosis in pediatric-onset systemic lupus erythematosus (pSLE).

Methods

Twenty subjects 9–19 years of age with pSLE underwent ABPM, peripheral endothelial function testing, carotid-femoral pulse wave velocity/analysis for aortic stiffness, and carotid intima-media thickness. We assessed the prevalence of non-dipping and other ABPM abnormalities. Pearson or Spearman rank correlation tests were used to evaluate relationships between nocturnal BP dipping, BP load (% of abnormally elevated BPs over 24-h), and vascular outcome measures.

Results

The majority (75%) of subjects had inactive disease, with mean disease duration of 3.2 years (± 2.1). The prevalence of non-dipping was 50%, which occurred even in the absence of nocturnal or daytime hypertension. Reduced diastolic BP dipping was associated with poorer endothelial function (r 0.5, p = 0.04). Intima-media thickness was significantly greater in subjects with non-dipping (mean standard deviation score of 3.0 vs 1.6, p = 0.02). In contrast, higher systolic and diastolic BP load were associated with increased aortic stiffness (ρ 0.6, p = 0.01 and ρ 0.7, p < 0.01, respectively), but not with endothelial function or intima-media thickness.

Conclusion

In a pSLE cohort with low disease activity, isolated nocturnal BP non-dipping is prevalent and associated with endothelial dysfunction and atherosclerotic changes. In addition to hypertension assessment, ABPM has a promising role in risk stratification and understanding heterogeneous mechanisms of cardiovascular disease in pSLE.
A transient CRISPR/Cas9 expression system for genome editing in Trypanosoma brucei
Authors: Shaw Sebastian , Knüsel Sebastian , Hoenner Sarah , Roditi Isabel
Published: June 2020

Objective

Generation of knockouts and in situ tagging of genes in Trypanosoma brucei has been greatly facilitated by using CRISPR/Cas9 as a genome editing tool. To date, this has entailed using a limited number of cell lines that are stably transformed to express Cas9 and T7 RNA polymerase (T7RNAP). It would be desirable, however, to be able to use CRISPR/Cas9 for any trypanosome cell line.

Results

We describe a sequential transfection expression system that enables transient expression of the two proteins, followed by delivery of PCR products for gRNAs and repair templates. This procedure can be used for genome editing without the need for stable integration of the Cas9 and T7RNAP genes.
Effects of bone marrow mononuclear cells on induction of axonal sprouting in cortico-cortical and cortico-striatal pathways in an animal model of cortical ablation
Authors: dos Santos Sampaio Maria de Fátima , Giraldi-Guimarães Arthur , da Silva Lourenço Camila , Pereira Messias Gonzaga , Coimbra Norberto Cysne
Published: June 2020

Objectives

Many therapies have been proposed in order to investigate the mechanisms of neural repair associated with neurological diseases, including bone marrow mononuclear cells (BMMC) transplantation. However, there is evidence that some encephalic injuries are less responsive to neural repair, such as, for example, cortical ablation. On the other hand, some models of cortical ablation have shown functional recovery after BMMC transplantation. Thus, it is relevant to expand the knowledge of BMMC transplantation-induced neuroplasticity in animal models, considering a promising approach for the rehabilitation of patients with neurological diseases. Using an experimental model of cerebral cortex ablation in adult male Wistar rats, which is known to be poorly responsive to neuroplasticity, the aim of this study was to investigate the effects of BMMC on axonal sprouting in cortico-cortical and cortico-striatal pathways synaptic fields. An anterograde neurotracer was used to evaluate the distribution of axonal fibres.

Results

The results showed that BMMC were not able to significantly induce axonal sprouting in the evaluated synaptic fields. Our results reinforced the idea that cortical ablation may be less responsive to neuroplasticity and the beneficial effects of BMMC therapy depend on the particularities of a neural microenvironment intrinsic to a given cortical lesion.
Pluripotent stem cell-derived skeletal muscle fibers preferentially express myosin heavy-chain isoforms associated with slow and oxidative muscles
Authors: Incitti Tania , Magli Alessandro , Jenkins Asher , Lin Karena , Yamamoto Ami , Perlingeiro Rita C. R.
Published: June 2020

Background

Skeletal muscle function is essential for health, and it depends on the proper activity of myofibers and their innervating motor neurons. Each adult muscle is composed of different types of myofibers with distinct contractile and metabolic characteristics. The proper balance of myofiber types is disrupted in most muscle degenerative disorders, representing another factor compromising muscle function. One promising therapeutic approach for the treatment of these diseases is cell replacement based on the targeted differentiation of pluripotent stem cells (PSCs) towards the myogenic lineage. We have previously shown that transient induction of Pax3 or Pax7 in PSCs allows for the generation of skeletal myogenic progenitors endowed with myogenic regenerative potential, but whether they contribute to different fiber types remains unknown.

Results

Here, we investigate the fiber type composition of mouse PSC-derived myofibers upon their transplantation into dystrophic and non-dystrophic mice. Our data reveal that PSC-derived myofibers express slow and oxidative myosin heavy-chain isoforms, along with developmental myosins, regardless of the recipient background. Furthermore, transplantation of the mononuclear cell fraction re-isolated from primary grafts into secondary recipients results in myofibers that maintain preferential expression of slow and oxidative myosin heavy-chain isoforms but no longer express developmental myosins, thus indicating postnatal composition.

Conclusions

Considering oxidative fibers are commonly spared in the context of dystrophic pathogenesis, this feature of PSC-derived myofibers could be advantageous for therapeutic applications.
Three dimensional microcarrier system in mesenchymal stem cell culture: a systematic review
Authors: Koh Benson , Sulaiman Nadiah , Fauzi Mh Busra , Law Jia Xian , Ng Min Hwei , Idrus Ruszymah Bt Hj , Yazid Muhammad Dain
Published: June 2020

Stem cell-based regenerative medicine is a promising approach for tissue reconstruction. However, a large number of cells are needed in a typical clinical study, where conventional monolayer cultures might pose a limitation for scale-up. The purpose of this review was to systematically assess the application of microcarriers in Mesenchymal Stem Cell cultures. A comprehensive search was conducted in Medline via Ebscohost, Pubmed, and Scopus, and relevant studies published between 2015 and 2019 were selected. The literature search identified 53 related studies, but only 14 articles met the inclusion criteria. These include 7 utilised commercially available microcarriers, while the rest were formulated based on different surface characteristics, all of which are discussed in this review. Current applications of microcarriers were focused on MSC expansion and induction of MSCs into different lineages. These studies demonstrated that MSCs could proliferate in a microcarrier culture system in-fold compared to monolayer cultures, and the culture system could simulate a three-dimensional environment which induces cell differentiation. However, detailed studies are still required before this system were to be adapted into the scale of GMP manufacturing.
Low computational complexity methods for decoding of STBC in the uplink of a massive MIMO system
Authors: Mousavi Seyed Hosein , Pourrostam Jafar
Published: June 2020

Reducing the computational complexity of the modern wireless communication systems such as massive MIMO configurations is of utmost interest. In this paper, we propose algorithms which can be used to accelerate matrix inversion and reduce the complexity of common spatial multiplexing schemes in massive MIMO systems. Here, we specifically investigate the performance of the proposed methods in systems that utilize STBC (Space-Time Block Code) in the uplink of dynamic massive MIMO systems for different scenarios. A multi-user system in which the base station is equipped with a large number of antennas and each user has two antennas is considered. In addition, users can enter or exit the system dynamically. For a given space-time block coding/decoding scheme, the computational complexity of the receiver will be significantly reduced by employing the proposed methods. The first approach is utilizing Neumann series to approximate the inverse matrix for linear decoders. The second tactic is reducing the computational complexity of the STBC decoders when a user is added to system or removed from it. In the proposed schemes, the matrix inversion for ZF and MMSE decoding is derived from inversing a partitioned matrix and Woodbury matrix identity. Furthermore, the suggested techniques can be utilized when the number of users is fixed but the CSI changes for a particular user. The mathematical equations for both approaches are derived and the complexity of the suggested methods is compared to the direct computation of the inverse matrix. Moreover, the performance of the proposed algorithms is evaluated in terms of the system BER (bit error rate). Evaluations confirm the effectiveness of the proposed approaches.
Concentration inequalities for upper probabilities
Authors: Tan Yuzhen
Published: June 2020

In this paper, we obtain a Bernstein-type concentration inequality and McDiarmid’s inequality under upper probabilities for exponential independent random variables. Compared with the classical result, our inequalities are investigated under a family of probability measures, rather than one probability measure. As applications, the convergence rates of the law of large numbers and the Marcinkiewicz–Zygmund-type law of large numbers about the random variables in upper expectation spaces are obtained.
Development and validation of an LC-MS/MS method for monitoring larotrectinib, a tropomyosin-related kinase inhibitor, in mouse and human plasma and application to pharmacokinetic studies
Authors: Chae Yoon-Jee , Song Yoo-Kyung , Chae Song-Hee , Kim Min Ju , Kang Jong Soon , Lee Jae-Young , Koo Tae-Sung , Lee Kyeong-Ryoon
Published: June 2020

Larotrectinib is an orally administered drug and the first and only selective pan-tropomyosin receptor kinase (TRK) inhibitor in clinical development to treat cancer patients harboring a neurotrophic receptor tyrosine kinase gene fusion. In this study, an analytical method to quantify the TRK inhibitor in mouse and human plasma was developed and validated using LC-MS/MS following protein precipitation with acetonitrile. Larotrectinib and an internal standard (carbamazepine) were separated from endogenous substances using an Xterra C18 column with acetonitrile containing 0.1% formic acid as the mobile phase. The ions m/z 429.8 → 342.8 for larotrectinib and m/z 237.0 → 194.0 for carbamazepine detected in multiple reaction monitoring mode were used for the quantitation. The detector response of larotrectinib was linear within the concentration range 5–10,000 ng/mL with a correlation coefficient (r2) of not less than 0.999. The intra- and inter-day precision and accuracy were less than 10.48% and within − 8.99%, respectively, in mouse and human plasma. Larotrectinib was stable under various storage and handling conditions, and no significant matrix effect was observed in both mouse and human plasma. Finally, the assay was successfully applied to the pharmacokinetic study of larotrectinib after its intravenous and oral administration to mice.
Estimation of temporal and spatial variation of sound speed in ocean from GNSS-A measurements for observation using moored buoy
Authors: Kinugasa Natsuki , Tadokoro Keiichi , Kato Teruyuki , Terada Yukihiro
Published: June 2020

Using Global Navigation Satellite System–Acoustic (GNSS-A) technique, we have been developing observation system on a moored buoy for continuous monitoring of seafloor crustal deformation. The sound speed structure near a warm current has heterogeneity, which is the main cause of a seafloor positioning error. Assuming a sloping structure, previous studies proposed sound speed model to reduce positioning error. We examined the validity of the model by comparing the estimated structure with the actual structure measured at multiple points around our observation site. The result shows that the gradient parameter estimated from GNSS-A data acquired by vessel is appropriate. The numerical examination indicates that modeling error caused by the misinterpretation of the depth of gradient layer occurs, and it can be suppressed by performing acoustic ranging at the point near the centroid of units. From the calculation of estimation error of sound speed variation, the predicted acoustic ranging error observed using the moored buoy staying near the centroid is 9.0 cm or below. Therefore, seafloor displacement can be detected with centimeter class via moored buoy in the basin of a warm current.
Impact of sitagliptin combination therapy and hypoglycemia in Japanese patients with type 2 diabetes: a multi-center retrospective observational cohort study
Authors: Saito Tomoyuki , Ohmura Hirotoshi , Nojiri Shuko , Daida Hiroyuki
Published: June 2020

Background

Patients with diabetes are at higher risk of developing polypharmacy because of the high frequency of comorbidities. There have been several reports on the hypoglycemic risk of the combination of hypoglycemic agents and other medications. This study aimed to investigate the hypoglycemic risk of drug-drug interaction between sitagliptin and other oral hypoglycemic agents or antihypertensive agents in Japanese patients with type 2 diabetes.

Methods

From January 2010 to March 2012, a total of 3247 patients were recruited and evaluated at outpatient clinics at Juntendo University Hospital, other satellite hospitals, and private clinics. This study was a sub-analysis of the Sitagliptin Registration Type 2 Diabetes-Juntendo Collaborating Project. Participants were limited to those treated with oral hypoglycemic agents, excluding insulin users, to investigate the association of the first hypoglycemic events with oral hypoglycemic agents or other medications within 6 months after starting sitagliptin. The factors related to the first hypoglycemic event were analyzed using Cox regression analysis.

Results

In total, 2956 patients with a mean age of 65.1 ± 11.3 years were included. A total of 46 hypoglycemic events (1.6%) were observed. One patient had severe hypoglycemia followed by emergency transport to the hospital. Sitagliptin was not associated with hypoglycemia, but its combination with sulfonylurea (hazard ratio: 4.42, 95% confidential interval: 1.36–14.42) or β-blocker (hazard ratio, 3.50, 95% confidential interval: 1.54–7.96) was significantly associated with hypoglycemia.

Conclusions

The drug-drug interactions between sitagliptin and sulfonylurea or β-blocker likely increases the hypoglycemic risk in Japanese patients with type 2 diabetes. Pharmacists should consider potential adverse events from drug-drug interaction in type 2 diabetes with polypharmacy, particularly those who are managed by several doctors or clinics.
Network analysis as a tool for humanitarian protection: research and practice
Authors: Cachia Romina , Holgado Ramos Daniel
Published: June 2020

In this article, we explore how network analysis could be used for humanitarian protection. Our objective is bringing together what is known about the role of networks for humanitarian aid intervention and examining how it could be used to respond to emergencies, through interventions which can aid and improve different aspects of the humanitarian protection. Based on this previous research, we develop a systematic framework aimed at informing researchers and practitioners on the different applications of network analysis and visualisations for humanitarian protection in two main areas: (1) to protect individuals and (2) to enable protection at the community level. We believe that the versatility of social network analysis is worth investigating in the context of humanitarian protection.
Translational simulation for rapid transformation of health services, using the example of the COVID-19 pandemic preparation
Authors: Brazil Victoria , Lowe Belinda , Ryan Leanne , Bourke Rachel , Scott Clare , Myers Simone , Kaneko Hellen , Schweitzer Jane , Shanahan Brenton
Published: June 2020

Healthcare simulation has significant potential for helping health services to deal with the COVID-19 pandemic. Rapid changes to care pathways and processes needed for protection of staff and patients may be facilitated by a translational simulation approach—diagnosing changes needed, developing and testing new processes and then embedding new systems and teamwork through training. However, there are also practical constraints on running in situ simulations during a pandemic—the need for physical distancing, rigorous infection control for manikins and training equipment and awareness of heightened anxiety among simulation participants. We describe our institution’s simulation strategy for COVID-19 preparation and reflect on the lessons learned—for simulation programs and for health services seeking to utilise translational simulation during and beyond the COVID-19 pandemic. We offer practical suggestions for a translational simulation strategy and simulation delivery within pandemic constraints. We also suggest simulation programs develop robust strategies, governance and relationships for managing change within institutions—balancing clinician engagement, systems engineering expertise and the power of translational simulation for diagnosing, testing and embedding changes.
The COVID-19 response must integrate people living with HIV needs in Sub-Saharan Africa: the case of Mali
Authors: Sagaon-Teyssier Luis , Yattassaye Adam , Bourrelly Michel , Dembélé Keïta Bintou , Spire Bruno
Published: June 2020

The first COVID-19 cases in Mali were reported almost 1 month after the first case in the African continent. However, the outbreak continues to spread faster there than in other countries which, along with Mali, successfully tackled the 2014 Ebola outbreak in Africa. Given this context, specific actions targeting people living with HIV (PLWH) are needed to reinforce prevention. Community-based involvement is crucial to ensure continuity of care and treatment for PLWH. Furthermore, the health of frontline healthcare workers must take priority in any actions taken. The long-established trustful relationship between NGOs and PLWH in Mali is indispensable to disseminate key messages about COVID-19.
The China-UK Global Health Support Programme: looking for new roles and partnerships in changing times
Authors: Husain Lewis , Bloom Gerald , McPherson Sam
Published: June 2020

China’s engagement in global affairs has changed substantially in the 2010s. One aspect of the country’s global reorientation has been its increased interest in, and willingness to play a role in, global health. In the early 2010s, the UK Department for International Development (DFID) initiated a collaboration with the Chinese government on a programme to support the country to play a greater and more effective global role in health and explore how the UK and China could work together on issues of key concern and contribute to improved global development outcomes. The programme worked with key Chinese agencies to carry out capacity building, support analysis of China’s approaches to engagement in global health governance and assistance, and provide support to government decision making. It also trialled several small-scale interventions in third countries through which Chinese agencies gained experience of working on health programmes overseas. The article reports on the main findings of an evaluation commissioned by DFID to learn from the programme. The programme provided support at a key time in China’s global reorientation; however, there is a need for continued development of capacity and systems for China to play the role envisaged by the country’s leadership. There is also a need for continued exploration on the part of China and partners of how to effectively collaborate to support improved global outcomes.