bluuebunny/crossref_metadata_2025 huggingface dataset:
Intersecting inequalities, gender and adolescent health in Ethiopia
Authors: Jones Nicola , Pincock Kate , Baird Sarah , Yadete Workneh , Hamory Hicks Joan
Published: June 2020

Background

Until recently, global public health initiatives have tended to overlook the ways that social factors shape adolescent health, and particularly how these dynamics affect the specific needs of adolescents in relation to information about puberty, menstruation and sexual health. This article draws on mixed methods data from rural and urban areas of Ethiopia to explore how access to health information and resources - and subsequently health outcomes - for adolescents are mediated by gender and age norms, living in different geographical locations, poverty, disability and migration.

Methods

Data was collected in 2017–2018 for the Gender and Adolescence: Global Evidence (GAGE) mixed-methods longitudinal research baseline in three regions of Ethiopia (Afar, Amhara and Oromia). Quantitative data was collected from over 6800 adolescents and their caregivers, with qualitative data obtained from a sub-sample of 220 adolescents, their families and communities. Adolescent participants shared their experiences of health, illness and nutrition over the previous year; their knowledge and sources of information about sexual and reproductive health and puberty; and their attitudes toward sexual and reproductive health. Regression analysis was used to explore differences by gender, age, rural/urban residence, and disability status, across a set of adolescents’ health knowledge and other outcomes in the quantitative data. Intersectional analysis was used in analysing the qualitative data.

Results

Analysis suggested that gender inequality intersects with age, disability and rural/urban differences to shape young people’s access to information about puberty, with knowledge about this topic particularly lacking amongst younger adolescents in rural areas. Drought and lack of access to clean water exacerbates health challenges for adolescents in rural areas, where a lack of information and absence of access to preventive healthcare services can lead to permanent disability. The research also found that gaps in both school-based and alternative sources of education about puberty and menstruation reinforce stigma and misinformation, especially in rural areas where adolescents have higher school attrition rates. Gendered cultural norms that place high value on marriage and motherhood generate barriers to contraceptive use, particularly in certain rural communities.

Conclusions

As they progress through adolescence, young people’s overall health and access to information about their changing bodies is heavily shaped by intersecting social identities. Structural disadvantages such as poverty, distress migration and differential access to healthcare intersect with gender norms to generate further inequalities in adolescent girls’ and boys’ health outcomes.
pH-dependent nanodiamonds enhance the mechanical properties of 3D-printed hyaluronic acid nanocomposite hydrogels
Authors: Lim Dae Gon , Kang Eunah , Jeong Seong Hoon
Published: June 2020

Nanocomposite hydrogels capable of undergoing manufacturing process have recently attracted attention in biomedical applications due to their desired mechanical properties and high functionality. 3D printing nanocomposite hydrogels of hyaluronic acid (HA)/nanodiamond (ND) revealed that the addition of ND with the low weight ratio of 0.02 wt% resulted in higher compressive force and gel breaking point, compared with HA only nanocomposites. These HA nanocomposite hydrogels loaded with surface functionalized ND allowed for the enforced compressive stress to be tuned in a pH-dependent manner. HA nanocomposite hydrogels with ND-OH at pH 8 showed an increase of 1.40-fold (0.02%: 236.18 kPa) and 1.37-fold (0.04%: 616.72 kPa) the compressive stress at the composition of 0.02 wt% and 0.04 wt, respectively, compared to those of ND-COOH (0.02%: 168.31 kPa, 0.04%: 449.59 kPa) at the same pH. Moreover, the compressive stress of HA/ND-OH (0.04 wt%) at pH 8 was mechanically enhanced 1.29-fold, compared to that of HA/ND-OH (0.04 wt%) at pH 7. These results indicate that the tunable buffering environment and interaction with the long chains of HA at the molecular level have a critical role in the dependency of the mechanical properties on pH. Due to the pH stability of the ND-OH nanophase, filament-based processing and layer-based deposition at microscale attained enforced mechanical properties of hydrogel. Fine surface tuning of the inorganic ND nanophase and controlled 3D printing leads to improved control over the pH-dependent mechanical properties of the nanocomposite hydrogels reported herein.
Structural vulnerabilities and HIV risk among sexual minority female sex workers (SM-FSW) by identity and behavior in Baltimore, MD
Authors: Glick Jennifer L. , Lim Sahnah , Beckham S. Wilson , Tomko Catherine , Park Ju Nyeong , Sherman Susan G.
Published: June 2020

Background

Research suggests sexual minority female sex workers (SM-FSW) face elevated structural vulnerability and HIV risk compared to their heterosexual counterparts. Structural vulnerabilities reflect societal level factors (e.g., sexism, homophobia, racism) that constrain an individual’s agency, particularly related to health outcomes. This study examines the association between SM status by identity and behavior, structural vulnerability, and HIV risk among a sample of street-based FSW.

Methods

The current study utilizes baseline data from the SAPPHIRE study, a prospective cohort of cis gender and transgender FSW in Baltimore, MD, recruited through targeted time-location sampling from April 2016 to January 2017. The current analysis focuses on cisgender women. The baseline survey ascertained demographics, substance use, intimate partner violence (IPV), and sex work characteristics. Multivariable models were constructed using self-identity and behaviorally defined SM status as independent variables with vulnerability outcomes (e.g., injection drug use, injection speedball, binge drinking, homelessness, physical IPV, ever had a pimp, and being a minor at sex work entry (age < 18)) as dependent variables.

Results

Of the participants (n = 247), 25.5% (n = 63) self-identified as a SM by identity (e.g., gay or bisexual), and 8.5% (n = 21) reported SM behavior (e.g., same-gender sexual behavior) in the past 3 months. In multivariable logistic regression models, SM status by identity was associated with increased odds of injection drug use, binge drinking, homelessness, physical IPV, and being a minor at sex work entry. SM status by behavior was associated with increased odds of binge drinking, homelessness, ever having a pimp, and being a minor at sex work entry.

Conclusion

The study indicates disproportionate structural vulnerability and heightened HIV risk among SM-FSW, as compared to their heterosexual counterparts, with differences in their profile by sexual identity and behavior. Findings suggest a need for nuanced interventions tailored to these populations.
Baseline prevalence and correlates of HIV and HCV infection among people who inject drugs accessing a syringe services program; Miami, FL
Authors: Bartholomew Tyler S. , Onugha Jason , Bullock Corinne , Scaramutti Carolina , Patel Hardik , Forrest David W. , Feaster Daniel J. , Tookes Hansel E.
Published: June 2020

Background

Blood-borne viral infections, such as HIV and hepatitis C (HCV), are common infections among people who inject drugs (PWID). This study aims to determine the prevalence of HIV and HCV infection among PWID accessing the first legal syringe services program (SSP) in the state of Florida, along with examining baseline correlates of HIV and HCV infection.

Methods

Baseline behavioral enrollment assessments of 837 participants accessing an SSP for the first time were analyzed. Patients self-reporting or testing HIV or HCV positive at the enrollment visit were included. Socio-demographic, drug use, and injection-related risk behaviors in the last 30 days were compared across groups defined by all combinations of HIV and HCV serostatus.

Bivariate and multivariable logistic regression models were used to assess correlates of baseline HCV and HIV infection independently.

Results

Overall prevalence for HCV and HIV infection were 44.4% and 10.2%, respectively. After adjusting for confounders, the most significant correlates of baseline HCV infection were age (aOR = 1.01), lower education level (aOR = 1.13), currently homeless (aOR = 1.16), injecting more than seven times a day (aOR = 1.14), reusing syringes (aOR = 1.18), and sharing injection equipment (aOR = 1.13). The most significant predictors of baseline HIV infection were age (aOR = 1.01), non-Hispanic Black race (aOR = 1.28), Hispanic ethnicity (aOR = 1.12), gay or bisexual orientation (aOR = 1.22), and methamphetamine injection (aOR = 1.22). In addition, heroin injection (aOR = 0.92) was significantly associated with a lower odds of HIV infection.

Discussion/conclusion

Baseline behavioral predictors differed between HIV infection and HCV infection among participants accessing syringe services. Understanding the risk factors associated with each infection should be considered when developing additional harm reduction interventions tailored for diverse PWID populations served at SSPs.
Factor structure and reliability of Persian version of hospital anxiety and depression scale in patients with breast cancer survivors
Authors: Hajian-Tilaki Karimollah , Hajian-Tilaki Erfaneh
Published: June 2020

Introduction

Anxiety and depression are significant concerns in breast cancer patients, and it may remain for a long term after primary treatments. The hospital anxiety and depression scale (HADS) is widely used to measure depressive and anxiety symptoms in clinical practices. The purpose of this study was to assess the psychometric properties of the Persian version of this scale in Iranian breast cancer survivors.

Methods

A total of 305 patients with breast cancer, refered to Cancer Hospital in northen Iran and completed the primary treatments were enrolled in. All patients responded to a 14-item HADS. We performed confirmatory factor analysis (CFA) to examine the factor structure of HADS and the item-scale analysis in order to estimate the item reliability and consider the Cronbach’s alpha as a measure of internal consistency.

Results

With a threshold of ≥8, the prevalence of anxiety and depression symptoms (moderate/severe) was 78.9 and 66.9%, respectively. The Cronbach’s alpha coefficients for anxiety and depression were 0.81 and 0.78, respectively. The CFA confirmed the two-factor structure model for HADS, indicating a good fitting summary indexes (χ2/df = 2.83, NFI = 0.88, RFI = 0.82, IFI = 0.92, CFI = 0.92, and RMSEA = 0.078).

Conclusion

The CFA and item reliability analysis have indicated an excellent psychometric property of the Persian version of HADS to measure depressive and anxiety symptoms in breast cancer survivors. Thus, HADS is a useful screening tool to identify post-breast cancer anxiety and depressive disorders.
Survival outcomes of neoadjuvant versus adjuvant chemotherapy in triple-negative breast cancer: a meta-analysis of 36,480 cases
Authors: Xia Lin-Yu , Hu Qing-Lin , Zhang Jing , Xu Wei-Yun , Li Xiao-Shi
Published: June 2020

Background

The survival outcomes of neoadjuvant chemotherapy (NACT) versus adjuvant chemotherapy (ACT) for patients with triple-negative breast cancer (TNBC) remain unclear. Therefore, in this study, a meta-analysis was conducted to analyze current evidence on the survival outcomes of NACT versus ACT in TNBC.

Methods

A systematic search was performed on the PubMed and Embase databases to identify relevant articles investigating the survival outcomes of NACT versus ACT in TNBC.

Results

A total of nine studies involving 36,480 patients met the selection criteria. Among them, 10,728 (29.41%) received NACT, and 25,752 (70.59%) received ACT. The pathological complete response (pCR) rate was 35% (95% CI = 0.23–0.48). Compared with ACT, the overall survival (OS) of NACT was poor (HR = 1.59; 95% CI = 1.25–2.02; P = 0.0001), and there was no significant difference in disease-free survival (DFS) between the two treatments (HR = 0.85; 95% CI = 0.54–1.34; P = 0.49). NACT with pCR significantly improved the OS (HR = 0.53; 95% CI = 0.29–0.98; P = 0.04) and DFS (HR = 0.52; 95% CI = 0.29–0.94; P = 0.03), while the OS (HR = 1.18; 95% CI = 1.09–1.28; P < 0.0001) and DFS (HR = 2.36; 95% CI = 1.42–3.89; P = 0.0008) of patients with residual disease (RD) following NACT were worse compared to those receiving ACT.

Conclusion

These findings suggest that, for TNBC, NACT with pCR is superior to ACT in improving OS and DFS, and it turns to be opposite when patients are receiving NACT with RD.
Comparable endocrine and neuromuscular adaptations to variable vs. constant gravity-dependent resistance training among young women
Authors: Arazi Hamid , Salek Lida , Nikfal Elham , Izadi Mani , Tufano James J. , Elliott Bradley T. , Brughelli Matt
Published: June 2020

Background

Variable resistance has been shown to induce greater total work and muscle activation when compared to constant resistance. However, little is known regarding the effects of chronic exposure to variable resistance training in comparison with constant resistance training. The aim of the present study was therefore to examine the effects of chain-loaded variable and constant gravity-dependent resistance training on resting hormonal and neuromuscular adaptations.

Methods

Young women were randomly assigned to variable resistance training (VRT; n = 12; age, 23.75 ± 3.64 years; and BMI, 26.80 ± 4.21 kg m−2), constant resistance training (CRT; n = 12; age, 23.58 ± 3.84 years; BMI, 25.25 ± 3.84 kg m−2), or control (Con; n = 12; age, 23.50 ± 2.93 years; BMI, 27.12 ± 12 kg m−2) groups. CRT performed 8-week total-body free-weight training three times per week with moderate-to-high intensity (65–80% 1RM; periodized). VRT was the same as CRT but included variable resistance via chains (15% of total load). Resting serum samples were taken before and after the 8-week intervention for GH, IGF-1, cortisol, myostatin, and follistatin analyses.

Results

Both VRT and CRT groups displayed moderate-to-large significant increases in GH (197.1%; ES = 0.78 vs. 229.9%; ES = 1.55), IGF-1 (82.3%; ES = 1.87 vs. 66%; ES = 1.66), and follistatin (58.8%; ES = 0.80 vs. 49.15%; ES = 0.80) and decreases in cortisol (− 19.9%; ES = − 1.34 vs. − 17.1%; ES = − 1.05) and myostatin (− 26.9%; ES = − 0.78 vs. − 23.2%; ES = − 0.82). Also, VRT and CRT resulted in large significant increases in bench press (30.54%; ES = 1.45 vs. 25.08%; ES = 1.12) and squat (30.63%; ES = 1.28 vs. 24.81%; ES = 1.21) strength, with no differences between groups.

Conclusions

Implementing chain-loaded VRT into a periodized resistance training program can be an effective alternative to constant loading during free-weight RT among untrained young women.
Effects of transcranial direct current stimulation with virtual reality on upper limb function in patients with ischemic stroke: a randomized controlled trial
Authors: Yao Xiaoling , Cui Lijun , Wang Jixian , Feng Wuwei , Bao Yong , Xie Qing
Published: June 2020

Background

Non-invasive brain stimulation techniques have been shown in several studies to improve the motor recovery of the affected upper-limbs in stroke patients. This study aims to investigate whether or not cathodal transcranial direct current stimulation (c-tDCS), combined with virtual reality (VR), is superior to VR alone in reducing motor impairment and improving upper limb function and quality of life in stroke patients.

Methods

Forty patients who suffered ischemic stroke between 2 weeks to 12 months were recruited for this single-blind randomized control trial. The patients were randomly assigned either to an experimental group who receiving c-tDCS and VR, or a control group receiving sham stimulation and VR. The cathodal electrode was positioned over the primary motor cortex (M1) of the unaffected hemisphere. The treatment session consisted of 20 min of daily therapy, for 10 sessions over a 2-week period. The outcome measures were the Fugl-Meyer Upper Extremity (FM-UE), the Action Research Arm Test (ARAT) and the Barthel Index (BI).

Results

The two groups were comparable in demographic characteristic and motor impairment. After 2 weeks of intervention, both groups demonstrated significant improvement in FM-UE, ARAT and BI scores (P<0.05).The experiment group demonstrated more improvement in FM-UE than the control group (10.1 vs. 6.4, p = 0.003) and, ARAT (7.0 vs 3.6, p = 0.026) and BI (12.8 vs 8.5, p = 0.043).

Conclusions

The findings from our study support that c-tDCS, along with VR, can facilitate a stronger beneficial effect on upper limb motor impairment, function and quality of life than VR alone in patients with ischemic stroke.

Trial registration

The study was registered in the Chinese Clinical Trial Registry (ChiCTR1800019386) in November 8, 2018-Retrospectively registered.
A detached leaf assay for testing transient gene expression and gene editing in cowpea (Vigna unguiculata [L.] Walp.)
Authors: Juranić Martina , Nagahatenna Dilrukshi S. K. , Salinas-Gamboa Rigel , Hand Melanie L. , Sánchez-León Nidia , Leong Weng Herng , How Tracy , Bazanova Natalia , Spriggs Andrew , Vielle-Calzada Jean-Philippe , Koltunow Anna M. G.
Published: June 2020

Background

The legume cowpea (Vigna unguiculata L.) is extensively grown in sub-Saharan Africa. Cowpea, like many legumes has proved recalcitrant to plant transformation. A rapid transient leaf assay was developed for testing gene expression and editing constructs prior to stable cowpea transformation, to accelerate cowpea and legume crop improvement.

Results

Attempts to develop a transient protoplast system for cowpea were unsuccessful. Leaflets from plants 3–4 weeks post-germination were age selected to establish a rapid Agrobacterium (Agro) infiltration-mediated transient system for efficacy testing of gene expression and CRISPR/Cas9 gene editing constructs. In planta, Agro-infiltration of leaflets with fluorescent expression constructs, resulted in necrosis. By contrast, Agro-infiltration of detached leaflets with an Arabidopsis (At) ubiquitin3 promoter:ZsGreen construct, followed by culture on solid nutrient medium resulted in fluorescence in over 48% of leaf cells. Expression efficiency was leaf age-dependent. Three cowpea meiosis genes were identified for CRISPR/Cas9 gene-editing, with the forward aim of meiosis-knock out for asexual seed induction in cowpea. Constructs were designed and tested containing candidate gene-specific guide RNAs, expressed using either the cowpea or Arabidopsis U6 promoters with Cas9 expression directed by either the Arabidopsis 40S ribosomal protein or parsley ubiquitin4-2 promoters. Leaflets were infiltrated with test gene-editing constructs and analytical methods developed to identify gene-specific mutations. A construct that produced mutations predicted to induce functional knockout of in the VuSPO11-1 meiosis gene was tested for efficacy in primary transgenic cowpea plants using a previously established stable transformation protocol. Vuspo11-1 mutants were identified, that cytologically phenocopied spo11-1 mutants previously characterized in Arabidopsis, and rice. Importantly, a biallelic male and female sterile mutant was identified in primary transgenics, exhibiting the expected defects in 100% of examined male and female meiocytes.

Conclusion

The transient, detached cowpea leaf assay, and supporting analytical methods developed, provide a rapid and reproducible means for testing gene expression constructs, and constructs for inducing mutagenesis in genes involved in both vegetative and reproductive developmental programs. The method and tested editing constructs and components have potential application for a range of crop legumes.
Good syndrome with cytomegalovirus hepatitis: successful resection of Thymoma: a case report
Authors: Isobe Sho , Sano Atsushi , Otsuka Hajime , Azuma Yoko , Koezuka Satoshi , Makino Takashi , Sakai Takashi , Ito Takafumi , Maeda Tadashi , Ejima Kozue , Homma Sakae , Iyoda Akira
Published: June 2020

Background

Good syndrome is a rare condition, manifesting as immunodeficiency due to hypogammaglobulinemia associated with thymoma. Herein, we present a patient with Good syndrome whose thymoma was resected after treatment of cytomegalovirus hepatitis.

Case presentation

The patient was a 45-year-old woman presenting with fever, cough, and nasal discharge, and was diagnosed with thymoma and hypogammaglobulinemia. She subsequently developed cytomegalovirus hepatitis that was treated by immunoglobulin. After resolution of the hepatitis, she underwent thymectomy through a left anterior thoracotomy. Her postoperative course was uneventful, and while receiving ongoing immunoglobulin therapy, she has been doing well without signs of infection.

Conclusions

Management of infections is important for patients with Good syndrome. To minimize the risk of perioperative infection, we should take care while planning the surgical approach and procedure.
Do investigator meetings improve recruitment rates in clinical trials? A retrospective before-and-after study of data from nine multi-centre clinical trials
Authors: Mitchell E. J. , Godolphin P. J. , Meakin G. , Sprange K.
Published: June 2020

Background

Poor recruitment in clinical trials is well-documented. In large, multi-centre trials, communication between the coordinating centre and trial sites is essential. A commonly used communication tool is the hosting of an investigator/collaborator meeting, which offers an opportunity for sites to re-train and receive trial updates, learn from each other, share best practice and troubleshoot issues. Anecdotally, there is a perception that recruitment rates may increase after holding such a meeting. The aim of this before-and-after study was to examine any changes in recruitment after an investigator meeting.

Methods

We conducted a retrospective study of nine trials at the Nottingham Clinical Trials Unit (NCTU) that were open to recruitment between 2014 and 2018. In the 8 weeks prior to the date of the investigator meeting, 82 sites (across nine trials) were open to recruitment; 60 of which attended the meeting, 22 who did not. Using meeting attendance data available in Trial Master Files (TMF) and recruitment data from randomisation datasets, we examined recruitment rates in the 8 weeks prior to and following the date of the investigator meeting.

Results

For the 82 sites included, 284 participants were recruited in the 8 weeks prior to the meeting, with a further 300 participants recruited in the 8 weeks post meeting. This gives a mean change in weekly recruitment of 0.073 (− 0.129, 0.275) per site, demonstrating no statistically significant increase in recruitment after the investigator meeting. For the 60 attending sites, recruitment increased from 254 participants prior to the meeting to 271 post meeting, giving a 0.100 (− 0.160, 0.360) mean change in weekly recruitment per site, providing no evidence that recruitment rates increase following an investigator meeting.

Conclusion

There is no statistical evidence to conclude that holding an investigator meeting increases recruitment in the 8 weeks following the meeting. Thus, if the meeting has been held in the belief that it will have a positive impact upon recruitment, trialists may wish to consider other evidence-based strategies known to increase recruitment rates. However, since there are a variety of reasons why an investigator meeting may be held, trialists should continue to consider this as a communication strategy with sites.
Zoonotic potential of Enterocytozoon bieneusi in pre-weaned Korean native calves
Authors: Hwang Sunwoo , Shin Seung-Uk , Kim SuHee , Ryu Ji-Hyoung , Choi Kyoung-Seong
Published: June 2020

Background

Enterocytozoon bieneusi is the most common microsporidian species infecting humans and various animals worldwide. To date, there has been limited information on the prevalence of infection and genotypes of E. bieneusi in cattle in the Republic of Korea. Therefore, this study investigated the prevalence and genotypes of E. bieneusi circulating in pre-weaned Korean native calves and determined the age pattern of E. bieneusi infection and the relationship between E. bieneusi infection and diarrhea.

Methods

The prevalence of E. bieneusi infection in pre-weaned Korean native calves was screened by polymerase chain reaction. PCR-positive products were sequenced to determine the genotype of E. bieneusi. A Chi-square analysis was used to compare the association between diarrhea and the infection rate of E. bieneusi in each age range or for all ages.

Results

PCR and sequencing analysis revealed an overall prevalence (16.9%, 53/314) of E. bieneusi in pre-weaned calves. The prevalence of E. bieneusi was highest in September (36.2%), followed by March (28.3%). Enterocytozoon bieneusi infection was associated with diarrhea in calves (χ2 = 5.82, P = 0.016). Our results also indicated that E. bieneusi infection was significantly associated with calf age (χ2 = 11.61, P = 0.003), and the prevalence of E. bieneusi infection was significantly higher in calves aged 21–40 days-old (odds ratio: 2.90, 95% confidence interval: 1.54–5.45; P = 0.001) than in those aged 1–20 days-old. Interestingly, the association between E. bieneusi infection and diarrhea was observed only in calves aged 1–20 days-old (χ2 = 5.82, P = 0.010). We identified three known genotypes, BEB4 (n = 12), BEB8 (n = 21) and J (n = 16), and three novel genotypes, BEB8-like (n = 21), KCALF1 (n = 1) and KCALF2 (n = 1). The genotype BEB8 was the most prevalent among all age groups. All genotypes identified in this study exhibited zoonotic potential.

Conclusions

To our knowledge, this is the first report of the genotype BEB4 in pre-weaned Korean native calves. Zoonotic E. bieneusi infection was prevalent in pre-weaned calves, indicating that cattle may play an important role as a reservoir host for E. bieneusi transmission to humans.
Age-structured vectorial capacity reveals timing, not magnitude of within-mosquito dynamics is critical for arbovirus fitness assessment
Authors: Mayton E. Handly , Tramonte A. Ryan , Wearing Helen J. , Christofferson Rebecca C.
Published: June 2020

Background

Transmission dynamics of arboviruses like Zika virus are often evaluated by vector competence (the proportion of infectious vectors given exposure) and the extrinsic incubation period (EIP, the time it takes for a vector to become infectious), but vector age is another critical driver of transmission dynamics. Vectorial capacity (VC) is a measure of transmission potential of a vector-pathogen system, but how these three components, EIP, vector competence and vector age, affect VC in concert still needs study.

Methods

The interaction of vector competence, EIP, and mosquito age at the time of infection acquisition (Ageacquisition) was experimentally measured in an Aedes aegypti-ZIKV model system, as well as the age-dependence of probability of survival and the willingness to bite. An age-structured vectorial capacity framework (VCage) was then developed using both EIPMin and EIPMax, defined as the time to first observed minimum proportion of transmitting mosquitoes and the time to observed maximum proportion of transmitting mosquitoes.

Results

The within-mosquito dynamics of vector competence/EIP were not significant among treatments where mosquitoes were exposed at different ages. However, VCage revealed: (i) age-dependence in vector-virus interactions is important for transmission success; (ii) lower vector competence but at shorter EIPs was sufficient for transmission perpetuation; and (iii) R0 may be overestimated by using non-age-structured VC.

Conclusions

The results indicate that ultimately the temporal component of the virus-vector dynamics is most critical, especially when exposure occurred at advanced mosquito age. While our study is limited to a single virus-vector system, and a multitude of other factors affect both vector competence and mosquito mortality, our methods can be extrapolated to these other scenarios. Results indicate that how ‘highly’ or ‘negligibly’ competent vectors are categorized may need adjustment.
Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis: the ANSWER cohort study
Authors: Ebina Kosuke , Hirano Toru , Maeda Yuichi , Yamamoto Wataru , Hashimoto Motomu , Murata Koichi , Takeuchi Tohru , Shiba Hideyuki , Son Yonsu , Amuro Hideki , Onishi Akira , Akashi Kengo , Hara Ryota , Katayama Masaki , Yamamoto Keiichi , Kumanogoh Atsushi , Hirao Makoto
Published: June 2020

Background

This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of 7 biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib (TOF), one of the janus kinase inhibitors, in bDMARDs-naïve and bDMARDs-switched patients with rheumatoid arthritis (RA).

Methods

This study assessed 3897 patients and 4415 treatment courses with bDMARDs and TOF from 2001 to 2019 (2737 bDMARDs-naïve courses and 1678 bDMARDs-switched courses [59.5% of switched courses were their second agent], female 82.3%, baseline age 57.4 years, disease duration 8.5 years; rheumatoid factor positivity 78.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate 4.3; concomitant prednisolone [PSL] dose 6.1 mg/day [usage 42.4%], and methotrexate [MTX] dose 8.5 mg/week [usage 60.9%]). Treatment courses included abatacept (ABT; n = 663), adalimumab (ADA; n = 536), certolizumab pegol (CZP; n = 226), etanercept (ETN; n = 856), golimumab (GLM; n = 458), infliximab (IFX; n = 724), tocilizumab (TCZ; n = 851), and TOF (n = 101/only bDMARDs-switched cases). Drug discontinuation reasons (categorized into lack of effectiveness, toxic adverse events, non-toxic reasons, or remission) and rates were estimated at 36 months using Gray’s test and statistically evaluated after adjusted by potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX usage, starting date, and number of switched bDMARDs) using the Fine-Gray model.

Results

Cumulative incidence of drug discontinuation for each reason was as follows: lack of effectiveness in the bDMARDs-naïve group (from 13.7% [ABT] to 26.9% [CZP]; P < 0.001 between agents) and the bDMARDs-switched group (from 18.9% [TCZ] to 46.1% [CZP]; P < 0.001 between agents); toxic adverse events in the bDMARDs-naïve group (from 4.6% [ABT] to 11.2% [ETN]; P < 0.001 between agents) and the bDMARDs-switched group (from 5.0% [ETN] to 15.7% [TOF]; P = 0.004 between agents); and remission in the bDMARDs-naïve group (from 2.9% [ETN] to 10.0% [IFX]; P < 0.001 between agents) and the bDMARDs-switched group (from 1.1% [CZP] to 3.3% [GLM]; P = 0.9 between agents).

Conclusions

Remarkable differences were observed in drug retention of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases.
The first composite score predicting Digital Ulcers in systemic sclerosis patients using Clinical data, Imaging and Patient history—CIP-DUS
Authors: Friedrich S. , Lüders S. , Klotsche J. , Burmester G. R. , Riemekasten G. , Ohrndorf S.
Published: June 2020

Background

Digital ulcers (DU) present a challenging complication in systemic sclerosis (SSc). The aim of this study was to combine clinical characteristics and imaging methods to a composite score for the prediction of DU in SSc patients.

Methods

Seventy-nine SSc patients received clinical examination, their patient history was taken and nailfold capillaroscopy (NC), colour Doppler ultrasonography (CDUS) and fluorescence optical imaging (FOI) of the hands were performed at baseline. Newly developed DU over a period of approximately 12 months were registered. We used criteria with area under the curve (AUC) of at least 0.6 in regard to the development of these new DU to create the score (CIP-DUS, clinical features, imaging, patient history—digital ulcer score).

Results

Twenty-nine percent of all SSc patients developed new DU during follow-up (48.1% diffuse, 18.4% limited SSc). Based on the cross-validated (cv) AUC, a weight (cvAUC > 0.6 and ≤ 0.65: 1; cvAUC > 0.65 and ≤ 0.7: 2; cvAUC > 0.7: 3) was assigned to each selected parameter. The performance of the final CIP-DUS was assessed with and without the CDUS/FOI component. For the scleroderma patterns in NC, three points were appointed to late, two to active and one point to early capillaroscopy pattern according to Cutolo et al. The CIP-DUS including the CDUS and FOI parameters resulted in a good diagnostic performance (AUC after cross-validation: 0.83, 95%CI 0.74 to 0.92) and was well calibrated (chi-square = 12.3, p = 0.58). The cut-off associated with the maximum of sensitivity and specificity was estimated at ≥ 10 points resulting in a sensitivity of 100% and specificity of 74% for new DU during follow-up. Excluding CDUS and FOI parameters leads to a non-statistically significant lower performance (AUC after cross-validation: 0.81, 95%CI 0.72 to 0.91). However, including CDUS and FOI resulted in a better classification of patients in respect to the outcome new DU in follow-up due to significantly better reclassification performance (NRI = 62.1, p = 0.001) and discrimination improvement (IDI = 9.7, p = 0.01).

Conclusion

A new score was introduced with the aim to predict digital ulcers. If applied correctly and with the new imaging techniques proposed, all patients at risk of digital ulcers throughout 12 months could be identified.
The predictive value of red cell distribution width for stroke severity and outcome
Authors: Shahsavarinia Kavous , Ghavam Laleh Younes , Moharramzadeh Payman , Pouraghaei Mahboob , Sadeghi-Hokmabadi Elyar , Seifar Fatemeh , Hajibonabi Farid , Khamnian Zhila , Farhoudi Mehdi , Mafi Sara
Published: June 2020

Objectives

In the present study, we sought to investigate the association between red cell distribution width (RDW) and stroke severity and outcome in patients who underwent anti-thrombolytic therapy with tissue plasminogen activator (tPA).

Results

In this prospective study, 282 stroke patients who underwent tPA injection were included. The categorization of RDW to < 12.9% and > 13% values revealed insignificant difference in stroke severity score, accounting for the mean 36-h NIHSS of 8.19 ± 8.2 in normal RDW values and 9.94 ± 8.28in higher RDW group (p = 0.64). In seventh day, NIHSS was 6.46 ± 7.28 in normal RDW group and was 8.52 ± 8.35 in increased RDW group (p = 0.058). Neither the 36-h, nor the seventh day and 3-month mRS demonstrated significant difference between those with normal and higher RDW values.
Harnessing peripheral DNA methylation differences in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to reveal novel biomarkers of disease
Authors: Vasanthakumar Aparna , Davis Justin W. , Idler Kenneth , Waring Jeffrey F. , Asque Elizabeth , Riley-Gillis Bridget , Grosskurth Shaun , Srivastava Gyan , Kim Sungeun , Nho Kwangsik , Nudelman Kelly N. H. , Faber Kelley , Sun Yu , Foroud Tatiana M. , Estrada Karol , Apostolova Liana G. , Li Qingqin S. , Saykin Andrew J. ,   for the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: June 2020

Background

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease impacting an estimated 44 million adults worldwide. The causal pathology of AD (accumulation of amyloid-beta and tau), precedes hallmark symptoms of dementia by more than a decade, necessitating development of early diagnostic markers of disease onset, particularly for new drugs that aim to modify disease processes. To evaluate differentially methylated positions (DMPs) as novel blood-based biomarkers of AD, we used a subset of 653 individuals with peripheral blood (PB) samples in the Alzheimer’s disease Neuroimaging Initiative (ADNI) consortium. The selected cohort of AD, mild cognitive impairment (MCI), and age-matched healthy controls (CN) all had imaging, genetics, transcriptomics, cerebrospinal protein markers, and comprehensive clinical records, providing a rich resource of concurrent multi-omics and phenotypic information on a well-phenotyped subset of ADNI participants.

Results

In this manuscript, we report cross-diagnosis differential peripheral DNA methylation in a cohort of AD, MCI, and age-matched CN individuals with longitudinal DNA methylation measurements. Epigenome-wide association studies (EWAS) were performed using a mixed model with repeated measures over time with aPvalue cutoff of 1 × 10−5to test contrasts of pairwise differential peripheral methylation in AD vs CN, AD vs MCI, and MCI vs CN. The most highly significant differentially methylated loci also tracked with Mini Mental State Examination (MMSE) scores. Differentially methylated loci were enriched near brain and neurodegeneration-related genes (e.g.,BDNF, BIN1, APOC1) validated using the genotype tissue expression project portal (GTex).

Conclusions

Our work shows that peripheral differential methylation between age-matched subjects with AD relative to healthy controls will provide opportunities to further investigate and validate differential methylation as a surrogate of disease. Given the inaccessibility of brain tissue, the PB-associated methylation marks may help identify the stage of disease and progression phenotype, information that would be central to bringing forward successful drugs for AD.
Pulp stem cells with hepatocyte growth factor overexpression exhibit dual effects in rheumatoid arthritis
Authors: Dong Xiwen , Kong Fanxuan , Liu Chao , Dai Shiyun , Zhang Yuning , Xiao Fengjun , Zhang Huan , Wu Chu-Tse , Wang Hua
Published: June 2020

Background

To investigate the therapeutic effect of human dental pulp stem cells (DPSCs) transfected with adenovirus expressing hepatocyte growth factor (HGF) in a mouse model of collagen-induced arthritis (CIA).

Methods

DPSCs were modified with Ad-HGF to produce HGF-overexpressing DPSCs, DPSCs-HGF. In experimental mouse CIA model, DPSCs-HGF and DPSCs-Null (modified with Ad-Null) were engrafted via intravenously after disease onset, which was determined by the presence of joint swelling. The therapeutic effects on joints were evaluated at 49 days after collagen injection by histopathological analysis and microcomputed tomography imaging. The inflammatory cytokines were analyzed both in sera and joints via MILLIPLEX kit and immunohistochemical staining, respectively, and the regulatory T cells (Tregs) were analyzed in peripheral blood by using flow cytometry. Furthermore, primary fibroblast-like synoviocytes were isolated, colony formation analysis and FACS were performed to evaluate the effect of HGF on the proliferation and cell cycle of FLSs. Western blot assay was carried out to clarify the signal pathway of HGF-cMet.

Results

We found that without HGF modification, DPSC transfusion was helpful in controlling autoimmune status, local synovitis, and bone erosion after intravenous administration. However, HGF-modified DPSCs have dual role in rheumatoid arthritis (RA). In the early phase, HGF overexpression inhibited RA progression by its immunosuppressive effects, while in the late phase, HGF promoted synovitis by activating fibroblast-like synoviocytes to produce pathogenic IL-6, accelerating cell proliferation and inducing apoptosis resistance via phosphorylating the c-Met/Akt pathway. The overall effect of HGF modification attenuated the therapeutic effect of DPSCs.

Conclusions

Our study provides a comprehensive evaluation of the therapeutic effect of DPSCs in the mouse model and a primary answer to the divergence of whether HGF is harmful or helpful in RA.
Tumour-to-liver ratio determined by [68Ga]Ga-DOTA-TOC PET/CT as a prognostic factor of lanreotide efficacy for patients with well-differentiated gastroenteropancreatic-neuroendocrine tumours
Authors: Kim Yong-il , Yoo Changhoon , Oh Seung Jun , Lee Sang Ju , Kang Junho , Hwang Hee-Sang , Hong Seung-Mo , Ryoo Baek-Yeol , Ryu Jin-Sook
Published: June 2020

Background

Lanreotide is a long-acting somatostatin analogue with proven antitumour effects against well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumours (GEP-NETs). However, there are no globally established prognostic factors associated with the efficacy of lanreotide as a treatment for GEP-NETs. We investigated the prognostic value of [68Ga]Ga-DOTA-TOC positron emission tomography (PET)/computed tomography (CT) somatostatin receptor imaging for patients with WD GEP-NETs treated with lanreotide.

Methods

In this retrospective study, we included 31 patients with unresectable or metastatic WD GEP-NETs who received lanreotide and underwent [68Ga]Ga-DOTA-TOC PET/CT before receiving lanreotide. We captured the following clinicopathological variables: Eastern Cooperative Oncology Group (ECOG) performance status, primary tumour site, NET World Health Organization grade, existence of carcinoid symptoms, previous surgery, previous chemotherapy, and hepatic tumour volume assessed by CT or magnetic resonance imaging (MRI). We also assessed the following [68Ga]Ga-DOTA-TOC PET/CT variables: Krenning score, tumour-to-liver ratio (TLR), maximum standardized uptake value (SUVmax), whole tumour volume (WTV), and total receptor expression (TRE, WTV multiplied by SUVmean). The associations between these markers and progression-free survival (PFS) with lanreotide were analysed.

Results

The mean age was 55.1 ± 15.5 years (range 16.0–81.0). The most common primary tumour site was the pancreas, followed by the stomach, and rectum. The median PFS interval with lanreotide was 14.4 months (range 1.3–34.9), with identified disease progression in 20 patients (64.5%). Among the [68Ga]Ga-DOTA-TOC PET/CT variables, TLR (< 8.1 vs. ≥ 8.1; p = 0.013), SUVmax (< 42.9 vs. ≥ 42.9; p = 0.037), and WTV (≥ 58.9 cm3 vs. < 58.9 cm3; p = 0.030) were significantly associated with PFS in the univariate analyses, but only TLR (hazard ratio 3.182 [95% CI 1.189–8.514], p = 0.021) remained an independent factor for PFS in the multivariate analysis.

Conclusions

Low TLR, determined via [68Ga]Ga-DOTA-TOC PET/CT, can be a factor of worse prognosis in patients with advanced WD GEP-NETs treated with lanreotide.
Characterization of a Trichinella spiralis aminopeptidase and its participation in invasion, development and fecundity
Authors: Guo Kai Xia , Bai Ying , Ren Hua Nan , Sun Xiang Yuan , Song Yan Yan , Liu Ruo Dan , Long Shao Rong , Zhang Xi , Jiang Peng , Wang Zhong Quan , Cui Jing
Published: June 2020

A Trichinella spiralis aminopeptidase (TsAP) has been identified in intestinal infectious larvae (IIL) and adult worms (AW), but its biological function in the T. spiralis life cycle is unknown. The aim of this study was to characterize TsAP and ascertain its functions in the invasion, development and fecundity of T. spiralis. Recombinant TsAP (rTsAP) was expressed and purified. rTsAP has strong immunogenicity. qPCR and western blotting show that TsAP was transcribed and expressed at all T. spiralis lifecycle stages, but the expression level of TsAP mRNA and proteins at IIL and AW stages was obviously higher than those in muscle larvae (ML) and newborn larvae (NBL). The IFT results reveal that TsAP was principally located at the cuticle and the intrauterine embryos of this nematode. rTsAP had the enzymatic activity of natural aminopeptidase to hydrolyze the substrate Leu-pNA with an optimal temperature of 50 °C and optimal pH of 8.0. rTsAP promoted the larval penetration into intestinal epithelial cells, whereas anti-rTsAP antibodies suppressed the larval intrusion; the promotion and suppression was dose-dependently related to rTsAP or anti-rTsAP antibodies. TsAP protein expression level and enzymatic activity were reduced by 50.90 and 49.72% through silencing of the TsAP gene by specific siRNA 842. Intestinal AW and muscle larval burdens, worm length and female reproductive capacity were significantly declined in mice infected with siRNA-transfected ML compared to the control siRNA and PBS group. These results indicate that TsAP participates in the invasion, development and fecundity of T. spiralis and it might be a candidate target for anti-Trichinella vaccines.
Characterization of humoral and cell-mediated immunity in rabbits orally infected with Encephalitozoon cuniculi
Authors: Jeklova Edita , Leva Lenka , Matiasovic Jan , Ondrackova Petra , Kummer Vladimir , Faldyna Martin
Published: June 2020

Encephalitozoonosis is a common infectious disease widely spread among rabbits.Encephalitozoon cuniculi, is considered as a zoonotic and emerging pathogen capable of infecting both immunocompetent and immunocompromised hosts. The aim of the study was to describe in detail the spread of theE. cuniculiin a rabbit organism after experimental infection and the host humoral and cellular immune response including cytokine production. For that purpose, healthy immunocompetent rabbits were infected orally in order to simulate the natural route of infection and euthanised at 2, 4, 6 and 8-weeks post-infection. Dissemination ofE. cuniculiin the body of the rabbit was more rapid than previously reported. As early as 2 weeks post-infection,E. cuniculiwas detected using immunohistochemistry not only in the intestine, mesenteric lymph nodes, spleen, liver, kidneys, lungs and heart, but also in nervous tissues, especially in medulla oblongata, cerebellum, and leptomeninges. Based on flow cytometry, no conspicuous changes in lymphocyte subpopulations were detected in the examined lymphoid organs of infected rabbits. Cell-mediated immunity was characterized by ability of both CD4+and CD8+T cells to proliferate after stimulation with specific antigens. Th1 polarization of immune response with a predominance of IFN-γ expression was detected in spleen, mesenteric lymph nodes and Peyer’s patches. The increased expression of IL-4 and IL-10 mRNA in mixed samples from the small intestine is indicative of balanced control of IFN-γ, which prevents tissue damage. On the other hand, it can enableE. cuniculito survive and persist in the host organism in a balanced host-parasite relationship. The Th17 immunity lineage seems to play only a minor role inE. cuniculiinfection in rabbits.
MicroRNA-466c-3p exerts protective effect on neuronal apoptosis and improves functional recovery post spinal cord injury via mitochondrial apoptotic pathway
Authors: An Yan , Li Jianing , Yuan Qiang , Fan Mingxing
Published: June 2020

Spinal cord injury (SCI) is involved with abnormal expression of miRNAs (miRs) which are responsible for some IIry injury responses which include apoptosis, inflammation and oxidative stress. Mechanisms involving miRs induced apoptosis still needs to be investigated. In the present work we developed a rat model of SCI, followed by microarray analysis for expression of miRs at various time points after SCI. The locomotor activity was assessed by Basso, Beattie and Bresnahan score, lesion volume was analyzed by cresyl violet staining and TUNEL staining for extent of apoptosis at various time points of post SCI. Numbers of miRs were altered after 2 weeks of SCI among which miR-466c-3p was the most significantly down-regulated. Transfection with miR-466c-3p mimics caused overexpression of miR-466c-3p, also improvement in functional recovery, decrease in apoptosis of neuronal cells and lesion size was observed in SCI rats. The Luciferase assay suggested that miR-466c-3p suppressed the expression of Bcl-2 (apoptosis regulator). It was also evidenced that upon restoring the levels of Bcl-2 with the help of pc-DNA3-Bcl-2 halted the attenuating action of miR-466c-3p in hydrogen peroxide exposed N9 microglia cells. The findings suggested that miR-466c-3p may inhibit mitochondrial apoptotic pathway via blocking Bcl-2 and cleaved capase-9/-3in rats after SCI. Altogether, the results suggested that miR-466c-3p may exert attenuating effect on functional recovery and inhibit the apoptosis of neuronal cells via halting the mitochondrial apoptosis cascade in SCI rats indicating that miR-466c-3p can be attractive therapeutic candidate in treating SCI.