bluuebunny/crossref_metadata_2025 huggingface dataset:
Anopheles arabiensis and Anopheles funestus s.s. biting pattern in Dielmo, an area of low level exposure to malaria vectors.
Authors: Doucoure Souleymane , Thiaw Omar , Wotodjo Amélé N. , Bouganali Charles , Diagne Nafissatou , Parola Philippe , Sokhna Cheikh
Published: April 2020

Background: In Dielmo, Senegal, the widespread use of long lasting insecticidal nets has decreased both the incidence of malaria and the density of the anopheles population. However, persistent low-level malaria transmission may hamper efforts to eliminate the disease. Therefore, continuous monitoring of the vector population is needed in order to improve knowledge of anopheles biting behaviour and to readjust control interventions.Methods: In 2015, anopheles were collected every month for a whole year and each specimen was identified using morphological and molecular techniques. The biting pattern of each species was analysed according to night (7pm–7am) and day (7am–11am) periods, the place of biting and the season. The ELISA CSP technique was used to evaluate the entomological inoculation rate (EIR).Results: An. arabiensis and An. funestus s.s. were found to be the main vectors biting human in Dielmo. Overall, the biting rate was low, at 3.84bites per night (bpn) and 1.27 bites per day (bpd), respectively. The EIR was 2.51 and 5.03 infected bites per year during the night and day, respectively. During the night, the An. arabiensis and An. funestus biting rate was 1.81 bpn and 1.71 bpn, respectively (p=0.80). During daylight hours, their aggressiveness decreased to 0.51 bpd and 0.73 bpd for An. arabiensis and An. funestus, respectively (p=0.30). During the night, depending on the seasons, only An. funestus displayed a significant outdoor biting behaviour both in the rainy and dry seasons, while during the day, no specific trend of indoor or outdoor biting was observed, regardless of the season for both vectors.Conclusion: This study highlighted low level anopheles nocturnal and diurnal biting and the associated risk of malaria transmission. It showed also the influence of the season on the indoor and outdoor biting pattern, indicating that the human population could be exposed all year round to a low level of anopheles bites. Control programs should increase awareness of the use of bed-nets throughout the year, particularly shortly after dawn when people are still indoors.
Prostate cancer detection improved by optimization of biopsy strategy: Bayesian framework of Network Meta -Analysis and HSROC model for diagnostic accuracy
Authors: Rahman Ilham Akbar , Fauzan Ilham , Syahrir Syakri , Nusaly Harry , Kasim Firdaus
Published: April 2020

Background: The increasing problem in prostate cancer is associated with over-diagnosis and over-treatment. The transrectal ultrasonography (TRUS)-guided biopsy as a current gold standard investigation poses low positive detection rate causing unnecessary biopsies. The choice of optimal biopsy strategy needs to be completely defined. Therefore, in the absence of direct statistical comparison and limited evidence, we undertook the advantage of Bayesian network meta-analysis and Bayesian prediction in the HSROC model to present a method for optimizing biopsy strategy in prostate cancer. Materials and Methods: Relevant 24 studies were comprehensively retrieved through online databases of EMBASE, MEDLINE, and CENTRAL up to February 2020. Markov chain Monte Carlo simulation and SUCRA were used to calculate the rank probability using odds ratio (OR) with 95% CI. HSROC model was used to formulate the predicted true sensitivity and specificity of each biopsy strategy. Data analysis was performed using STATA, R, and WinBUGS statistics. Results: Six different PCa biopsy strategies based on four outcomes were ultimately analyzed in this study with a total of 6768 patients. The rank probability showed that the overall PCa detection rate was higher in FUS+TRUS-GB, MRI-GB, and FUS-GB. In terms of clinically significant PCa detection, FUS+TRUS-GB, and FUS-GB had a relatively higher clinically significant detection rate. Moreover, MRI-GB, FUS-GB, and FUS+TRUS-GB were less associated with insignificant PCa detection rate. MRI-GB and FUS-GB had the highest predicted of true sensitivity and specificity. Conclusion: Taken together, in comprehensive consideration of four endpoints, our analysis highlights the important finding that FUS+TRUS-GB, FUS-GB, and MRI-GB showed their superiority compared with other strategies. TRUS-GB was more associated with over-diagnosis of insignificant PCa, lower sensitivity, and specificity.
Calcaneal Osteotomy “Safe Zone” for Avoiding Injury to the Lateral Plantar Artery: A Fresh Cadaveric Study
Authors: Tonogai Ichiro , Sairyo Koichi , Tsuruo Yoshihiro Tsuruo
Published: April 2020

Background Calcaneal osteotomy is used to correct hindfoot deformity. Pseudoaneurysms of the lateral plantar artery (LPA) have been reported following calcaneal osteotomy and are at risk of rupture. The vascular structures in close proximity to the calcaneal osteotomy have variable courses and branching patterns. However, there is little information on the “safe zone” during calcaneal osteotomy. This study aimed to identify the safe zone that avoids LPA injury during calcaneal osteotomy.Methods Enhanced computed tomography scans of 25 fresh cadaveric feet (13 male and 12 female specimens; mean age 79.0 years at time of death) were assessed. The specimens were injected with barium via the external iliac artery. A landmark line (line A) connecting the posterosuperior aspect of the calcaneal tuberosity and the origin of the plantar fascia was drawn and the shortest perpendicular distance between the LPA and line A was measured on sagittal images.Results The average perpendicular distance between the LPA and line A at its closest point was 15.2 ± 2.9 mm. In 2 feet (8.0%), the perpendicular distance between the LPA and line A at its closest point was very short (approximately 9 mm). In 18 of the 25 feet (72.0%), the point where the perpendicular distance from line A to the LPA was closest was the bifurcation of one of the medial calcaneal branches of the LPA, and in 7 feet (28.0%) the shortest perpendicular distance from line A to the LPA was the trifurcation of the LPA, medial plantar artery, and one of the medial calcaneal branches.Conclusion Calcaneal osteotomy performed more than 9 mm from line A could damage the LPA by overpenetration on the medial side. Calcaneal osteotomy on the medial side should be performed with caution to avoid iatrogenic injury to the LPA.Level of Evidence: IV, cadaveric study
Real-World Safety and Efficacy of Nivolumab in Advanced Squamous and Nonsquamous Non-Small-Cell Lung Cancer: A Retrospective Cohort Study in Croatia, Hungary and Malta
Authors: Vrdoljak Eduard , Jakopović Marko , Geczi Lajos , Bogos Krisztina , Bosković Lidija , Magri Claude , Bitar Lela , Bajić Žarko , Samaržija Miroslav
Published: April 2020

Background: There is a lack of real-world data on the safety and efficacy of nivolumab in patients with previously treated advanced non-small-cell lung cancer (NSCLC) especially in South East Europe, a region with particularly high incidence and an unfavorable mortality-to-incidence ratio for lung cancer. Methods: This is a multicenter, retrospective cohort study on patients with stage IIIB or IV disease with at least one previous systemic treatment who received nivolumab through an expanded-access program between 2015 and 2017 in Croatia, Malta and Hungary. The primary endpoint was the proportion of patients whose therapy was discontinued because of toxicity. Secondary endpoints were incidence of adverse events (AEs), objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: We analyzed data on 239 patients with a median (IQR) age of 62 (57-68), and 33% of them were women. Treatment was discontinued because of toxicity in 11.6% (95% CI 7.8% to 16.5%) of patients. The PFS was 6.4 (95% CI 5.2 to 8.6) months, and the median OS was 14.1 (10.6 to 18.0) months. Conclusions: The safety and efficacy of nivolumab in previously treated patients with advanced NSCLC in the real-world South East Europe clinical settings were consistent with the results of randomized clinical trials and comparable to the results from other countries.
Neurodevelopmental Outcome and Respiratory Management of Congenital Central Hypoventilation Syndrome: A case control study
Authors: Ogata Tomomi , Muramatsu Kazuhiro , Miyana Kaori , Ozawa Hiroshi , Iwasaki Motoki , Arakawa Hirokazu
Published: April 2020

Background: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by sleep apnea. Anoxia often occurs soon after birth, and it is important to prevent anoxia-mediated central nervous system complications; however, data on the relationship between respiratory management and the prognosis for intellectual development of patients with CCHS is scarce. Methods: We performed a retrospective chart review cohort study of patients with CCHS in Japan. We investigated the risk and prognostic factors for developmental outcomes and examined the disease in terms of its symptoms, diagnosis, complications, and treatment. Results: Of the 123 patients with CCHS included in the survey, 88 patients were 6 years old and older. They were divided into two group based on their IQ. Those treated using positive-pressure ventilation via tracheostomy in the first three months of life had a better developmental prognosis than those managed via tracheostomy after three months of age and those treated by ventilation using mask (OR = 3.80; 95% CI: 1.00–14.37, OR = 4.65; 95% CI: 1.11–19.37). There was no significant difference in physical development (P = 0.64). Conclusions: The best respiratory treatment for patients with CCHS is ventilation via tracheostomy, initiated ideally before the age of three months.
Serum level and clinical significance of vitamin E in children with allergic rhinitis
Authors: WANG Shi-yi , WANG Yin-feng , PAN Chun-chen , Sun Jingwu
Published: April 2020

Background: Allergic rhinitis (AR) has an increasing prevalence in children and its etiology has aroused wide concern. This study aimed to investigate the association between serum concentrations of vitamin E and allergic rhinitis (AR) to determine if the vitamin E level is correlated with the occurrence and severity of AR. Methods: A total of 113 children were enrolled in this cross-sectional study. Sixty-five children in the outpatient group were diagnosed with AR, and 48 healthy children were recruited as controls. All subjects underwent serum vitamin E measurements. Serum tototal IgE (tIgE), the five most common allergen- specific IgE (sIgE) levels and skin prick test (SPT) were measured in children with AR. The severity of AR was assessed with the nasal symptoms score. Results: Serum vitamin E levels were significantly lower in the AR group than in the normal children (p<0.001). A significant negative correlation was observed between serum vitamin E levels and sIgE as well as the SPT grade. Serum vitamin E levels were also inversely related to the nasal symptoms score; however, statistical significance was not found. Conclusions: A significantly lower vitamin E level was found in children with AR. Lower serum vitamin E levels play a role in the occurrence of AR in children. However, serum vitamin E levels were not statistically correlated with the severity of AR.
Establishment of a Pediatric Trigger Tool Based on Global Trigger Tool to Identify Adverse Drug Events of Children: Experience in a Chinese hospital
Authors: LIU YI , YAN JUN FENG , XIE YUN FEI , BIAN YUAN
Published: April 2020

Background: The Global Trigger Tool (GTT)，which is a method using “triggers” to review medical record retrospectively to identify possible adverse events. Several studies showed that the GTT was effective. However, there were only a few localized trigger tools that had been established to detect pediatric adverse drug events (ADEs) in China. This study aimed to establish a pediatric trigger tool based on GTT, to examine the performance by detecting pediatric inpatients ADEs in a Chinese hospital (a retrospective review), and to investigate the factors associating with the occurrence of ADEs. Methods: The triggers were established by three steps including literature search, triggers extraction and revision, and experts investigation. A retrospective cohort study was conducted to detect ADEs by using 200 pediatric inpatient records of Sichuan Provincial People's Hospital. Results: 33 preliminary triggers were established, and 2 rounds of experts investigation were conducted. Finally, 33 triggers were established. In the retrospective review, the positive trigger rate was 64.0%, while the positive predictive value (PPV) was 24.9%. The occurrence of inpatients with ADEs was 20.5%. ADEs/100 patients were 49.0. ADEs/1000 patients days were 46.89. The most common ADE categories were leukocyte abnormalities, skin lesions and platelet abnormalities. The severity of 39 ADEs was grade 1, 55 ADEs was grade 2, 4 ADEs was grade 3. The highest frequency of ADE-related drugs was antineoplastic, followed by antibacterial. The length of stay and the leukemia in the diagnosed diseases were positively correlated with ADEs . Conclusion : The 33 pediatric triggers may detect ADEs effectively, but still need to be optimized. This study may provide some references for further research in order to improve the rationality and safety of medication.
Bioinformatics analysis of epitope-based vaccine design against the novel SARS-CoV-2
Authors: Chen Hongzhi , Tang Lingli , Yu Xinling , Zhou Jie , Chang Yunfeng , Wu Xiang
Published: April 2020

Background: An outbreak of infection caused by SARS-CoV-2 recently has brought a great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of pandemic. This study aimed to predict the protective epitopes with bioinformatics methods and resources for vaccine development. Methods: ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DiscoTope 2.0 program. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forecasted epitopes were characterized for immunogen potential evaluation. Results: A total of 63 sequential B-cell epitopes on spike protein were predicted and 4 peptides (Spike315-324, Spike333-338, Spike648-663, Spike1064-1079) exhibited high antigenicity score and good surface accessibility. 10 residues within spike protein (Gly496, Glu498, Pro499, Thr500, Leu1141, Gln1142, Pro1143, Glu1144, Leu1145, Asp1146) are forecasted as components of discontinuous B-cell epitopes. The bioinformatics analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind class-I and class-II molecule respectively. The peptides (Nucleocapsid66-75, Nucleocapsid104-112) were predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. Conclusions: B-cell epitopes on spike protein and T-cell epitopes within nucleocapsid protein were identified and recommended for developing a protective vaccine against SARS-CoV-2.
Evaluation of antiparasitic therapy directly administered for the control of canine echinococcosis in an endemic area of hydatidosis.
Authors: Montalvo Raul , Huiza Alaina , Clemente Johana , Castañeda Lorena , Ccente Yoli , Nuñez Mayori , Arteaga Lizet , Balbuena Lizzeth , Inga Cristhian
Published: April 2020

Background: Echinococcosis remains endemic despite attempts to reduce the prevalence of this disease. The objective of the study was to evaluate the results of an intervention program based on antiparasitic therapy directly administered for the control of canine Echinococcosis in an endemic area of ​​hydatidosis.Methods: Fecal samples of the dogs were analyzed by coproantigen using the immunoenzymatic technique for the diagnosis of echinococcosis before and after the direct and observed administration of praziquantel 5mg by kg orally in three doses every 30 days each cycle was 2 times at year for two consecutive years.Results: Of a total of 252 dogs, 119 (47%) presented positive results to Echinococcus before the intervention. The adverse effects presented with the administration of praziquantel were: 13 (5.2%) dogs had vomiting, 6 (2.4%) dogs had diarrhea, 5 (2%) had drowsiness or lethargy, the most severe complication was death of 02 (0.8%) dogs after 7 days of the first dose. 229 dogs completed the 4 cycles of the administration of praziquantel. 03 (1.3%) dogs presented positive coproantigene after direct antiparasitic administration.Conclusions: Antiparasitic chemotherapy administered directly to the dogs periodically managed to reduce the prevalence of canine echinococcosis.
Continuous inhibition of Sonic hedgehog signaling effectively leads to differentiation of human-induced pluripotent stem cells into functional insulin-producing β cells
Authors: Lee Song , Joo Jae Hyun , Oh Ju Yun , Seo Eun Ha , Kim Yang Hee , Jun Eunsung , Shim In Kyoung , Kim Song Cheol
Published: April 2020

Background: Human-induced pluripotent stem cell (iPSC)-derived insulin-producing cells (IPCs) can be used for islet cell transplantation in type 1 diabetic patients and as patient-specific cells for the development of novel anti-diabetic drugs. Therefore, it is necessary develop a method for generating functional IPCs from iPSCs and simplifying the stepwise protocol. Methods: We compared combinations of small molecules that could efficiently induce the differentiation of cells into a definitive endoderm, and preferentially into islet precursor cells. IPCs, generated using the optimal combination of small molecules, were confirmed to demonstrate insulin secretion in response to glucose stimulation. Finally, we re-constructed spheroid IPCs and verified the optimized culture and maturation conditions. Results: It was confirmed by quantitative polymerase chain reaction that definitive endoderm-specific markers were expressed differently depending on the combination of the small molecules used. Small molecule SANT-1 induced the differentiation of cells into functional IPCs by acting as an inhibitor of Sonic hedgehog signaling. Images of 2D culture showed that IPCs were spheroid-shaped from day 5 and demonstrated sustained insulin secretion. We developed a simple differentiation method using small molecules that produced functional IPCs that responded efficiently to glucose stimulation in a relatively short time. Conclusions: We posit that this method along with a method that refines the process of differentiation can be used for growing IPCs that can be employed in clinical trials.
Diversity and Co-Occurrence Patterns of microbial Communities in the Fertilized Eggs of Thitarodes Insect, the Implication on the Occurrence of Chinese cordyceps
Authors: Guo Lian-Xian , Liu Xiao-Shan , Mai Zhan-Hua , Hong Yue-Hui , Zhu Qi-Jiong , Guo Xu-Ming , Tang Huan-Wen
Published: April 2020

Background

The large-scale artificial cultivation of Chinese cordyceps has not been widely implemented because the crucial factors triggering the occurrence of Chinese cordyceps have not been fully illuminated.

Methods

In this study, the bacterial and fungal structure of fertilized eggs in the host Thitarodes collected from 3 sampling sites with different occurrence rates of Chinese cordyceps (Sites A, B and C: high, low and null Chinese cordyceps, respectively) were analyzed by performing 16S RNA and ITS sequencing, respectively. And the intra-kingdom and inter-kingdom network were analyzed.

Results

For bacterial community, totally 4671 bacterial OTUs were obtained. α-diversity analysis revealed that the evenness of the eggs from site A was significantly higher than that of sites B and C, and the dominance index of site A was significantly lower than that of sites B and C ( P < 0.05). β-diversity analysis showed that the differences of bacterial community among the eggs from the three sampling sites were significantly different. OTU1 ( Wolbachia ) was the overwhelming predominant bacteria in the eggs from sites B and C. Although OTU4 ( Spiroplasma ) was detected in minor abundances, it showed distribution preference in the fertilized eggs from site A. For fungal community, totally 3318 fungal OTUs were obtained. Difference analysis showed significant differences among the three sites, while the differences were not as significant as that of bacterial community. In addition, ten fungal genera in the three most concerned Cordyceps families (Clavicipitaceae, Cordycipitaceae and Ophiocordycipitaceae) were detected in the fertilized eggs, while the most approved anamorph ( Hirsutella ) of Chinese cordyceps wasn’t discovered. Intra-kingdom (fungi) network analysis revealed more positive correlations and average degrees at sites A, and Inter-kingdom network analysis revealed more positive and negative correlations at sites A.

Discussion

The microbial community, especially the bacterial community in the fertilized eggs, might be significantly related with the occurrence of Chinese cordyceps, and Wolbachia might be the most significant microorganism negatively related with the occurrence. A closer correlation of the microbial community, especially closer fungal positive correlation, in the fertilized eggs might help for the occurrence of Chinese cordyceps.
Predictors of thyroglobulin in the lymph nodes recurrence of papillary thyroid carcinoma undergoing total thyroidectomy
Authors: Xing Zhichao , Qiu Yuxuan , Li Zhe , Zhang Lingyun , Fei Yuan , Zhu Jingqiang , Su Anping
Published: April 2020

Purpose: To investigate serum thyroglobulin (Tg) levels in recurrent papillary thyroid carcinoma (PTC) patients, thereby evaluating possible risk factors and structural features of lymph nodes (LNs) recurrence.Patients and Methods: All the patients with primary PTC who underwent total thyroidectomy (TT) with central or lateral neck dissection and then re-operated due to LNs recurrence between January 2013 and June 2018 were included. Patients were subdivided groups by different Tg levels. Results: This study included 60 patients with LNs recurrence. Of all, 49 patients underwent radioactive iodine (RAI) treatment. Maximum unstimulated Tg (uTg) ≥ 0.2 ng/mL were associated with larger diameter of recurrent LNs (P = 0.027), higher possibility of diameters of recurrent LNs ≥ 25mm (P = 0.023) and higher ratio of metastatic LNs (P < 0.001). Pre-RAI ablation serum-stimulated Tg (off-Tg) ≥ 1ng/mL and unstimulated Tg detected at 1 week after RAI ablation (on-Tg) ≥ 0.2 ng/mL were associated with larger diameter of recurrent LNs and higher possibility of diameters of recurrent LNs ≥ 25mm. Number of metastatic LNs ≥ 8 was an independent predictor for maximum uTg ≥ 0.2 ng/mL (OR = 8.767; 95% CI =1.392-55.216; P = 0.021). Ratio of metastatic LNs ≥ 25% was an independent predictor for off-Tg ≥ 1 ng/mL (OR = 20.997; 95% CI =1.649-267.384; P = 0.019). Conclusion: Tg-positive was associated with larger size of recurrent LNs. Number of metastatic LNs ≥8 could independently predict maximum uTg-positive. Ratio of metastatic LNs ≥ 25% was an independent predicator for off-Tg-positive.
Klotho inhibits H 2 O 2 -induced oxidative stress and apoptosis in periodontal ligament stem cells by regulating UCP2 expression
Authors: Zhu Lilei , Xie Hui , Liu Qingqing , Ma Fei , Wu Hao
Published: April 2020

Background Periodontitis, known as a human chronic inflammatory disease, has affected the life of millions of individuals. Known risk factors such as metabolic disease and oxidative stress have been reported to be closely associated with the initiation or development of periodontitis. However, the etiology of periodontitis remains unclear. Klotho, a single-pass transmembrane protein, has been widely reported to modulate cellular processes in various diseases. However, the role of Klotho in periodontitis is unknown.Results In this study, we designed and conducted a series of experiments to evaluate the role of Klotho in chronic periodontitis. Our experimental results showed that Klotho was downregulated in the gingival tissues, gingival crevicular fluid (GCF), and periodontal ligament stem cells (PDLSCs) of chronic periodontitis patients. Besides, Klotho upregulated the production of uncoupling protein 2 (UCP2) in H2O2-treated PDLSCs. In function, Klotho inhibited H2O2-induced oxidative stress and cellular apoptosis in PDLSCs. Moreover, the rescue assay suggested that UCP2 knock-down suppressed the effects of Klotho on H2O2-induced oxidative stress and apoptosis in PDLSCs.Conclusions In conclusion, we found that Klotho inhibits H2O2-induced oxidative stress and apoptosis in PDLSCs by regulating UCP2 expression. This novel discovery may provide a potential target for chronic periodontitis treatment.
An Exploratory Qualitative Study of Health Professional Perspectives on Clinical Outcomes in UK Orthotic Practice
Authors: Hall Natalie , Parker Daniel , Williams Anita Ellen
Published: April 2020

Background: Despite potential savings to the National Health Service, the collection of data on outcomes of NHS orthotic services is patchy. Indeed, several reports into orthotic services in the UK have reported a lack of data relating to outcomes of care and highlighted the need to routinely record outcomes to demonstrate efficacy of services. This research aimed to explore orthotic service professional perspectives on outcomes in orthotic practice. A secondary aim was to explore potential barriers to the routine use of outcome measure tools in practice.Methods: Following a review of the literature, an initial advisory group involving experts in the field was conducted. From this, semi-structured questions were developed, and a focus group was undertaken. Data from the focus group was transcribed and analysed using thematic analysis, creating themes and subthemes for discussion.Results: The participants considered a successful outcome as a ‘usable’ orthosis, this linked to a preference for evaluation of patient reported outcomes. The setting of realistic joint goals via patient education was seen as a method of improving outcomes. Barriers to collection of data were associated with inadequate technology to manage the ‘data burden’, lack of clinical time to complete and difficulties selecting outcome measure tools for a varied population. Issues around usability of current outcome measure tools were also highlighted. Participants discussed ways of addressing these barriers, such as the use of ‘snapshots’ and delegation of data collection. Conclusions:This research is unique in that it is the first-time orthotic service professional opinions have been analysed specifically relating to outcomes, outcome measure tools and possible barriers to their use. The participants acknowledged the relevance of outcome measure tools, identified barriers to use but had created novel ways to address barriers. Further, they indicated that to achieve good outcomes it was important to address service user expectations of treatment, discuss and establish joint goals for care at the outset and communicate/ educate on the clinical reasoning process. This research has contributed to current knowledge within the field of orthotics and may provide a theoretical basis for future research in the field.
The Envelope Protein of Tick-Borne Encephalitis Virus Influence Neuron Entry, Pathogenicity and Vaccine Protection
Authors: Lindqvist Richard , Rosendal Ebba , Asghar Naveed , Schreier Sarah , Lenman Annasara , Johansson Magnus , Dobler Gerhard , Bestehorn Marlena , Kröger Andrea , Överby Anna K
Published: April 2020

Background: Tick-borne encephalitis virus (TBEV) is considered to be the medically most important arthropod-borne virus in Europe. The symptoms of an infection ranges from subclinical to mild flu-like disease to lethal encephalitis. The exact determinants of disease severity are not known, however, the virulence of the strain as well as the immune status of the host are thought to be important factors for the outcome of the infection. Here we investigated virulence determinants in TBEV infection.Method: Mice were infected with different TBEV strains, and high virulent and low virulent TBEV were chosen. Sequence alignment were used to identify differences that were cloned to generate chimera virus. The infection rate of the parental and chimeric virus were evaluated in primary mouse neurons, astrocytes and MEFs. Neutralizing capacity of serum from individuals vaccinated with the FSME-IMMUN® and Encepur® or combined were evaluated.Results: We identified a highly pathogenic and neurovirulent TBEV strain, 93/783. Using sequence analysis, we identified the envelope (E) protein of 93/783 as a potential virulence determinant and cloned it into the less pathogenic TBEV strain Torö. We found that the chimeric virus specifically infected primary neurons more efficiently compared to wild type (WT) Torö and this correlated with enhanced pathogenicity in vivo. The E protein is also the major target of neutralizing antibodies, thus genetic variation in the E protein could influence the efficiency of the two available vaccines, FSME-IMMUN® and Encepur®. As TBEV vaccine breakthroughs have occurred in Europe, we choose to compare neutralizing capacity from individuals vaccinated with the two different vaccines or a combination of them. Our data suggest that the different vaccines do not perform equally well against the two Swedish strains.Conclusions: Our findings show that two amino acid substitutions of the E protein found in 93/783, A83T and A463S, enhanced Torö infection of neurons as well as pathogenesis in vivo, furthermore we found that genetic divergence from the vaccine strain resulted in lower neutralizing antibody titers in vaccinated individuals.
Which behaviour change techniques are effective to promote physical activity and reduce sedentary behaviour in adults: a factorial randomized trial of an e- and m-health intervention
Authors: Schroé Helene , Dyck Delfien Van , De Paepe Annick , Poppe Louise , Loh Wen Wei , Verloigne Maïté , Loeys Tom , De Bourdeaudhuij Ilse , Crombez Geert
Published: April 2020

BackgroundE- and m-health interventions are promising to change health behaviour. Many of these interventions use a large variety of behaviour change techniques (BCTs), but it’s not known which BCTs or which combination of BCTs contribute to their efficacy. Therefore, this study investigated the efficacy of three BCTs (i.e. action planning, coping planning and self-monitoring) and their combinations on physical activity (PA) and sedentary behaviour (SB).MethodsIn a 2(action planning: present vs absent) x2(coping planning: present vs absent) x2(self-monitoring: present vs absent) factorial trial, 473 adults from the general population used the self-regulation based e- and m-health intervention ‘MyPlan2.0’ for five weeks. All combinations of BCTs were considered, resulting in eight groups. Participants selected their preferred target behaviour, either PA (n = 335,age = 35.8,28.1% men) or SB (n = 138,age = 37.8,37.7% men), and were then randomly allocated to the experimental groups. Levels of PA (MVPA in minutes/week) or SB (total sedentary time in hours/day) were assessed at baseline and post-intervention using self-reported questionnaires. Linear mixed-effect models were fitted to assess the impact of the different combinations of the BCTs on PA and SB.ResultsFirst, overall efficacy of each BCT was examined. The delivery of self-monitoring increased PA (t = 2.735,p = 0.007) and reduced SB (t=-2.573,p = 0.012) compared with no delivery of self-monitoring. Also, the delivery of coping planning increased PA (t = 2.302,p = 0.022) compared with no delivery of coping planning. Second, we investigated to what extent adding BCTs increased efficacy. Using the combination of the three BCTs was most effective to increase PA (x2 = 8,849,p = 0.003) whereas the combination of action planning and self-monitoring was most effective to decrease SB (x2 = 3.918,p = 0.048). To increase PA, action planning was always more effective in combination with coping planning (x2 = 5.590,p = 0.014;x2 = 17.722,p < 0.001;x2 = 4.552,p = 0.033) compared with using action planning without coping planning. Of note, the use of action planning alone reduced PA compared with using coping planning alone (x2 = 4.389,p = 0.031) and self-monitoring alone (x2 = 8.858,p = 003), respectively.ConclusionsThis study provides indications that different (combinations of) BCTs may be effective to promote PA and reduce SB. More experimental research to investigate the effectiveness of BCTs is needed, which can contribute to improved design and more effective e- and m-health interventions in the future.Trial registrationThis study was preregistered as a clinical trial (ID number: NCT03274271). Release date: 20 October 2017, http://clinicaltrials.gov/ct2/show/NCT03274271
Adverse childhood experiences and the association with initiating Alcohol, and chat Consumption before age of 18, in school going adolescents, Ethiopia: cross sectional study
Authors: Tsehay Mekonnen , Necho Mogese , Belete Asmare
Published: April 2020

Background : Adverse childhood experiences (ACEs) were associated with poor health outcomes and health-threatening behaviors later in life. The objective of the present study was to investigate associations between adverse childhood experiences (ACEs) and early initiation of alcohol and chat use among school going adolescents.Methods : A cross-sectional study was performed with 546 school going adolescents. The ACE International Questionnaire (ACE-IQ) was used to assess ACEs, including emotional, physical, and sexual forms of abuse and neglect, as well as household dysfunction. Alcohol and chat use was assessed by questions prepared by authors. Multiple logistic regression models were used to examine the associations between overall ACE score and alcohol use and the potential moderating effects of confounders.Results : prevalence of chat chewing behavior was 26.6% followed by alcohol use 20%, and small number of student’s use cigarette smoking and other illicit drug users (0.9%) (ganja and Shisha) each. A total of 66.2% of participants reported at least one ACE, and 5.93% reported four or more ACEs. Increased ACE scores were associated with increased risks of drinking (adjusted odds ratio [AOR] = 1.09, 95% confidence intervals [CI]: 1.00–1.09), chronic disease (AOR =1.17, 95% CI: 1.06–1.28), depression (AOR = 1.37, 95% CI: 1.27–1.48), and posttraumatic stress disorder (AOR = 1.32, 95% CI: 1.23–1.42) in adulthood. After adjusting for confounding factors, the individual ACE components had different impacts on risk behavior and health, particularly on poor mental health outcomes in adulthood.Conclusions : Alcohol and Chat use was prevalent and public health concern among school going adolescents. ACEs were significantly associated with risk behaviors, alcohol and chat use may lead poor health and educational outcomes among adolescent students and numbers of ACEs have graded association. Social support, sex, residence, parent educational status and current level of depressive symptoms were significant modulating factors, which parents, school teachers, psychologists and adolescent health care providers should give concern to decrease the effect on school going adolescents.
Relationship between the cytotoxic activity of peripheral blood natural killer cells and recurrent miscarriage
Authors: Zhang Yong-Nu , Huang Chun-Yu , Lian Ruo-Chun , Xu Jian , Fu Yun-Feng , Zeng Yong , Tu Wen-Wei
Published: April 2020

Background: Peripheral natural killer (pNK) cells are granular lymphocytes of the innate immune system that can be recruited by the endometrium to participate in the decidualization and be in contact with the villus in the intervillous space. Moreover, pNK cells were thought to exert cytotoxicity to cytotrophoblast, especially in abnormal pregnancy. However, it is still controversial about the association between pNK cytotoxicity and RM so far. In this study, we aim to compare the percentage, immunophenotype and function of pNK cells between patients with RM and fertile controls.Methods: The peripheral blood was collected from 49 patients with RM and 11 fertile women in their middle luteal phase of the menstrual cycle. pNK cells were co-cultured with K562 cells at three different cell ratios to measure the cytotoxicity. The percentage of CD3-CD56+ pNK was analyzed by flow cytometry and quantified to evaluate the expression of cytotoxic granules (granzyme B, granulysin, and perforin), and the cell surface receptors related to pNK cell cytotoxicity (NKG2D, NKp30, NKp46, CD158a, CD158b) were also detected.Results: The general linear model analysis showed that pNK cell cytotoxicity in patients with RM was significantly lower than that in fertile controls. The RM group possessed a significantly lower level of granzyme B+ pNK cells and significantly higher level of CD158a+, CD158b+ pNK cells than that in the control group. However, there was no significant difference in the proportion of circulating CD3-CD56+ NK cells expressing the granzyme B, granulysin, perforin, NKG2D, NKp30, NKp46, CD158a, CD158b. Conclusions: Our results suggested that a lower pNK cytotoxicity might be associated with RM.
Prevalence and predictors of contraceptives use among women age (15-49) with induced abortion history in Ghana
Authors: Salifu Mohammed Gazali , Kamaldeen Mohammed
Published: April 2020

Background Abortion incidence in Ghana ranges from 27 per 1000 to 61 per 1000 women, causing major gynecological complications or problems and maternal mortality. Though, the use of modern contraceptives has been documented to be a reliable public health preventive measure towards reducing unwanted pregnancies, only 19% of women aged (15-49) with abortion history receive post-abortion contraception support. This study therefore aimed at determining the proportion and identifying predictors of contraceptives use in these underreported and vulnerable population.Methods This study used secondary data from the 2017 Ghana Maternal Health Survey (GMHS) for the analysis. The analysis is on a weighted sample of 3,039 women aged (15-49 years) with history of induced abortion. Both descriptive and inferential methods were employed. Chi- Square test, univariate and multivariate logistic regression techniques were used to assess statistical associations between the outcome variable and the predictors. Statistical significance was set at 95% confidence interval and p-values <0.05.Results Out of the 3039 participants, 37% (95% CI: 34.6, 38.84) used contraceptives. We identified women age, union, place of residence, knowledge of fertile period, total pregnancy outcomes, and region as strong significant (95% CI p<0.005) predictors of post induced abortion contraceptives use.Conclusion Contraceptives use among this vulnerable population is low. Therefore, there is the need to provide widespread access to post-abortion contraception services and enhance efforts to efficiently integrate the safe abortion practices law into health services in Ghana.
Scouting the Receptor Binding Domain of COVID-19: A Comprehensive Immunoinformatics Inquisition
Authors: Rehman Zaira , Fahim Ammad , Bhatti Muhammad Faraz
Published: April 2020

The December of 2019 witnessed emergence of worldwide outbreak by a novel strain of coronavirus termed COVID-19 with sequence similarity of overall 96.2% with BatCoV RaTG13 (coronavirus isolated from bat) and 94% sequence identity with Severe Acute respiratory syndrome Virus (SARS-CoV) that resulted in outbreak in 2002-2003. There is no therapeutic or preventive strategy like vaccine developed so far to overcome infection.The receptor binding domain (RBD) of COVID-19 for any potential vaccine epitopes were explored. The structure of RBD of COVID-19, BatCoV RaTG13 and bACE2 were chalked through homology modeling followed by molecular docking and structural validation. A comprehensive immunoinformatics approach mapped conserved peptide sequence on COVID-19 RBD for their B-, Helper T- & Cytotoxic T-cell epitope profile. The recognized epitopes were further studied and validated for their docking interaction with MHC-I and MHC-II alleles. Through immune-informatics approaches the study identified conserved B- and T-cell epitopes in RBD. The B-cell epitopes lying within the receptor binding motif, LFRKSN and SYGFQPT l were found to be highly antigenic. Among T-cell epitopes, the epitope CVADYSVLY and FTNVYADSF were antigenic and exhibited affinity for maximum number of MHC-I alleles. The T cell epitopes YRLFRKSNL, VYAWNRKRI displayed affinity for maximum number of MHC-II alleles. The docking analysis of the epitopes with MHC proteins revealed strong interactions of T-cell epitopes with MHC-I and MHC-II alleles. The overlapping epitope among B- and T-cells was YRLFRKSNL. The deployment of these epitopes in potential vaccine against COVID-19 may help in sweeping the COVID-19 infectious spread.
Can ACE2 receptor polymorphism predicts species susceptibility to SARS-CoV-2?
Authors: Devaux Christian A. , Pinault Lucile , Osman Ikram Omar , Raoult Didier
Published: April 2020

A novel severe acute respiratory syndrome coronavirus named SARS-CoV-2, emerged in China in December 2019 and recently spread worldwide causing more than 144,987 deaths from COVID-19 disease. Similar to SARS-CoV that was related to a bat-borne coronavirus, this new virus originated from Rhinolophus affinis bats. Because bats usually transmit their coronaviruses to intermediate animal hosts that in turn represent a source of virus able to cross the species barrier to finally infect humans, the identification of an intermediate animal reservoir was recently the subject of intense researches. At the very beginning it was claimed that a reptile (Ophiophagus hannah) was the intermediate host. This hypothesis was quickly eliminated to be replaced by the pangolin (Manis javanica) hypothesis. Yet, several other animal species were recently reported as possible intermediate hosts in between bats and humans. To determine which intermediate animal host could have infected the index case patient with SARS-CoV-2, we used multi-sequence alignment, 3-D structure analysis and electrostatic potential surface generation of the angiotensin I converting enzyme 2 (ACE2) that serves as cellular receptor for SARS-CoV-2. We report evidence that such in silico investigation is a powerful tool that may help identification of potential SARS-CoV-2 susceptible species and that positions K31and Y41 in the a1 ridge, N82 and N90 in the loop and a3 and K353 in loop and b5 play a major role for SARS-CoV-2 binding to ACE2.
All-in-One Dual CRISPR-Cas12a (AIOD-CRISPR) Assay: A Case for Rapid, Ultrasensitive and Visual Detection of Novel Coronavirus SARS-CoV-2 and HIV virus at the Point of Care
Authors: Ding Xiong , Yin Kun , Li Ziyue , Lalla Rajesh V. , Ballesteros Enrique , Sfeir Maroun M. , Liu Changchun
Published: April 2020

The recent outbreak of novel Coronavirus (SARS-CoV-2), the causative agent of COVID-19 disease, has spread rapidly all over the world. Human immunodeficiency virus (HIV) is another deadly virus and causes acquired immunodeficiency syndrome (AIDS). Rapid and early detection of these viruses will facilitate early intervention and prevent disease spread. Here, we present an All-In-One Dual CRISPR-Cas12a (termed "AIOD-CRISPR") assay method for simple, rapid, ultrasensitive, specific, one-pot, and visual detection of coronavirus SARS-CoV- 2 and HIV-1 virus. In our AIOD-CRISPR assay, a pair of crRNAs was introduced to initiate dual CRISPR-Cas12a-based detection and improve both detection sensitivity and fluorescence signals. The AIOD-CRISPR assay method was utilized to detect nucleic acids (DNA and RNA) of the SARS-CoV-2 and HIV-1 with a sensitivity of few copies. We validated our AIOD-CRISPR method by using COVID-19 swab samples and obtained consistent results with that of RT-PCR method. More importantly, we successfully demonstrated to use a low- cost hand warmer (~$ 0.3) as an incubator of our AIOD-CRISPR assay and detect COVID-19 patient samples within 20 minutes, enabling an instrument-free, visual detection of COVID-19 at the point of care. Thus, our method has significant potential for developing next-generation point-of-care molecular diagnostics.
Development of high affinity monobodies recognizing SARS-CoV-2 antigen
Authors: Du Yushen , Zhang Tian-hao , Meng Xiangzhi , Shi Yuan , Hu Menglong , Yuan Shuofeng , La Chit Ying , Li Shu-xing , Liu Siwei , Li Jiayan , Huang Haigen , Jian Hong , Chen Dongdong , Sheng Li , Hong Mengying , Olson Anders , Liao Hsiang-I , Chen Xiaojiang , Li Xinmin , Zhao Gexin , Roberts Richard W. , Chan Jasper F W , Jin Dong-Yan , Chen Irvin SY , Chen Honglin , Yuen Kwok-Yung , Hao Quan , Sun Ren
Published: April 2020

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a threat to global public health. Prompt patient identification and quarantine is the most effective way to control its rapid transmission, which can be facilitated by early detection of viral antigens. Here we present a platform to develop and optimize the fibronectin-based affinity-enhanced antibody mimetics (monobodies) for recognizing viral antigens. Specifically, we developed monobodies targeting SARS-CoV-2 nucleocapsid (N) protein. We showed that two monobodies, NN2 and NC2, bind to N protein’s N- and C-terminal domains respectively with a Kd in nM range.The specificity of the recognition was confirmed with co-immunoprecipitation and immunofluorescence assays. Furthermore, we demonstrated that one round of in vitro maturation using mRNA display can improve the binding affinity of monobodies. Machine learning algorithms were integrated with deep sequencing data for selecting candidates that improve the detection sensitivity of N. Using this pair of monobodies, we have developed an enzyme-linked immunosorbent assay (ELISA) for viral detection. We were able to detect recombinant N at 4 pg/ml and detect N in viral culture supernatant, with no cross-reactivity with other CoV. Integrating high-dense mutagenesis, mRNA display, deep sequencing and machine learning, this platform can be applied through iterations to identify and optimize monobodies against emerging viral antigens, potentiating point-of-care detection of communicable diseases in a cost-and time-sensitive manner.Authors Yushen Du, Tian-hao Zhang, Xiangzhi Meng, Yuan Shi, and Menglong Hu contributed equally to this work.