bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and treatment of viral hepatitis C in persons who use drugs: a prospective, multicenter outreach study in Flanders, Belgium
Authors: Busschots Dana , Kremer Cécile , Bielen Rob , Koc Özgür Muhammet , Heyens Leen , Dercon Eefje , Verrando Rita , Windelinckx Tessa , Maertens Griet , Bourgeois Stefan , Hens Niel , Matheï Catharina , Robaeys Geert
Published: May 2021

Background

Targeted screening for hepatitis C viral (HCV) infection is not yet widely executed in Belgium. When performed in people who use drugs (PWUD), it is mainly focused on those receiving opiate agonist therapy (OAT). We wanted to reach out to a population of difficult to reach PWUD not on centralized OAT, using non-invasive screening as a bridge to re-integration in medical care supported by facilitated referral to a specialist.

Methods

This was a prospective, multicenter cohort study in PWUD not enrolled in a centralized OAT program in a community-based facility in Limburg or OAT program in a community-based facility in Antwerp, Belgium, from October 2018 until October 2019. Two study teams recruited participants using an outreach method at 18 different locations. Participants were tested for HCV antibodies (Ab) by finger prick, and risk factors were assessed through a face-to-face questionnaire. Univariate analyses were used to assess the association between HCV Ab and each risk factor separately. A generalized linear mixed model was used to investigate the association between the different risk factors and HCV.

Results

In total, 425 PWUD were reached with a mean age of 41.6 ± 10.8, and 78.8% (335/425) were men. HCV Ab prevalence was 14.8% (63/425). Fifty-six (88.9%) PWUD were referred, of whom 37 (66.1%) were linked to care and tested for HCV RNA. Twenty-nine (78.4%) had a chronic HCV infection. Treatment was initiated in 17 (58.6%) patients. The adjusted odds for HCV Ab were highest in those with unstable housing 6 months before inclusion (p < .001, AOR 8.2 CI 95% 3.2–23.3) and in those who had ever shared paraphernalia for intravenous drug use (p < .001, AOR 6.2 CI 95% 2.5–16.0).

Conclusions

An important part tested positive for HCV. Treatment could be started in more than half of the chronically infected referred and tested positive for HCV-RNA. Micro-elimination is necessary to achieve the World Health Organization goals by 2030. However, it remains crucial to screen and link a broader group of PWUD to care than to focus solely on those who inject drugs.

Trial registration: clinicaltrials.gov NCT04363411, Registered 27 April 2020—Retrospectively registered.https://clinicaltrials.gov/ct2/show/NCT04363411?term=NCT04363411&draw=2&rank=1
Psychometric properties of the WHOQOL-BREF(PT) in a sample of elderly citizens
Authors: Goes Margarida , Lopes Manuel , Marôco João , Oliveira Henrique , Fonseca César
Published: May 2021

Background

The goal of this article was to research the psychometric properties of the WHOQOL-BREF(PT) instrument in a sample of elderly citizens residing in a rural area in their own homes or at family members’ or friends’ homes and to compare the results: (i) to those reported by the team of Portuguese researchers that undertaken the instrument's translation/validation to the Portuguese language and (ii) to those reported internationally by the World Health Organization Quality of Life group. An overall quality of life scoring (QOL24—all facets) is also proposed in this article as novelty. The correlation level between QOL24 and the instrument’s general facet was also investigated.

Methods

This was a cross-sectional study with a sample of 351 elderly citizens (46.4% males and 53.6% females) randomly selected from the official dataset of the Local Health Unit of Baixo Alentejo. All the data were collected by health professionals at the participants’ homes following the structured interview methodology and using the WHOQOL-BREF(PT) instrument. Three different structural equation models were developed: (i) a first-order confirmatory factor analysis, to assess the instrument’s psychometric properties; (ii) a hierarchical second-order confirmatory factor analysis model, to allow determining the QOL24 scoring; and (iii) a more generic structural equation model, to investigate the correlation level between QOL24 and the instrument’s general facet.

Results

The WHOQOL-BREF(PT) showed an “almost very good” goodness of fit (comparative fit index of 0.949 and Tucker-Lewis index of 0.943), an adequate internal consistency (Cronbach’s alpha: from 0.64 to 0.90; composite reliability: from 0.59 to 0.88) and tolerable convergent validity (average variance extracted: from 0.374 to 0.614). However, discriminant validity was not reached because strong correlations between the first-order factors (four QOL domains) were obtained, together with low values of the average variance extracted. The scoring of QOL domains and QOL24, determined as weighted averages (proposed in this article as novelty) were significantly different than those determined as unweighted averages. The standardized correlation coefficient between QOL24 and the instrument’s general facet was of 0.89 (statistically highly significant).

Conclusions

The WHOQOL-BREF(PT) is a psychometrically sound instrument to assess the QOL of the considered population sample. However, the QOL domains were found strongly intertwined. More studies are necessary to validate the weighted average scoring strategy of QOL domains and QOL24. Concurrent validity between QOL24 and the instrument’s general facet was considered as “strong”.
Correlation between steroid levels in follicular fluid and hormone synthesis related substances in its exosomes and embryo quality in patients with polycystic ovary syndrome
Authors: Yu Li , Liu Miao , Wang Zhenxin , Liu Te , Liu Suying , Wang Beili , Pan Baishen , Dong Xi , Guo Wei
Published: May 2021

Background

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with various manifestations and complex etiology. Follicular fluid (FF) serves as the complex microenvironment for follicular development. However, the correlation between the concentration of steroid in FF and the pathogenesis of PCOS is still unclear.

Methods

Twenty steroid levels in FF from ten patients with PCOS and ten women with male-factor infertility undergoing in vitro fertilization were tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to explore their possibly correlation with PCOS. Meanwhile, the mRNA levels of core enzymes in steroid synthesis pathway from exosomes of FF were also detected by qPCR.

Results

The estriol (p < 0.01), estradiol (p < 0.05) and prenenolone (p < 0.01) levels in FF of PCOS group were significantly increased, compared to the normal group, and the progesterone levels (p < 0.05) were decreased in PCOS group. Increased mRNA levels ofCYP11A, CYP19AandHSD17B2of exosomes were accompanied by the hormonal changes in FF. Correlation analysis showed that mRNA levels ofCYP11AandHSD17B2were negatively correlated with percent of top-quality embryos and rate of embryos develop to blastocyst.

Conclusion

Our results suggest that increased levels of estrogen and pregnenolone in follicular fluid may affect follicle development in PCOS patients, and the mechanism is partially related toHSD17B1,CYP19A1andCYP11A1expression change in FF exosomes.
Setting the global research agenda for community-based HIV service delivery through the faith sector
Authors: Ndlovu-Teijema Martha T. , Kok Maarten O. , van Elsland Sabine L. , Smeets Hilleen , Barstow David , van Rooyen Lyn , van Furth A. M.
Published: May 2021

Background

While leading AIDS organizations expect faith and health collaborations to play a crucial role in organizing and scaling up community-based HIV services, it is unclear how this can be realized. Little primary research has been conducted into which strategies for collaboration and service provision are most effective, efficient, scalable and sustainable. Seeking to align research with urgent needs, enhance coordination and increase the likelihood that results are used, this study aimed to set an inclusive global research agenda that reflects priority research questions from key stakeholders at the intersection of HIV healthcare and faith.

Methods

In order to develop this global research agenda, we drew from document analyses, focus group discussions, interviews with purposively selected key informants from all continents (policy-makers, healthcare providers, faith leaders, academics and HIV activists), an online questionnaire, and expert meetings at several global conferences. We carried out focus group discussions and interviews with faith leaders in South Africa. Other stakeholder focus groups and interviews were carried out online or in person in France, Switzerland, the Netherlands and South Africa, and virtual questionnaires were distributed to stakeholders worldwide. Respondents were purposively sampled.

Results

We interviewed 53 participants, and 110 stakeholders responded to the online questionnaire. The participants worked in 54 countries, with the majority having research experience (84%), experience with policy processes (73%) and/or experience as a healthcare provider (60%) and identifying as religious (79%). From interviews (N = 53) and questionnaires (N = 110), we identified 10 research themes: addressing sexuality, stigma, supporting specific populations, counselling and disclosure, agenda-setting, mobilizing and organizing funding, evaluating faith-health collaborations, advantage of faith initiatives, gender roles, and education. Respondents emphasized the need for more primary research and prioritized two themes: improving the engagement of faith communities in addressing sexuality and tackling stigma.

Conclusions

A wide range of respondents participated in developing the research agenda. To align research to the prioritized themes and ensure that results are used, it is essential to further engage key users, funders, researchers and other stakeholders, strengthen the capacity for locally embedded research and research uptake and contextualize priorities to diverse religious traditions, key populations and local circumstances.
Correction to: Cost-effectiveness evaluation of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine for children in Taiwan
Authors: Lu Chun-Yi , Chung Ching-Hu , Huang Li-Min , Kruger Eliza , Tan Seng-Chuen , Zhang Xu-Hao , Chiu Nan-Chang
Published: May 2021

An amendment to this paper has been published and can be accessed via the original article.
Equity-specific effects of interventions to promote physical activity among middle-aged and older adults: results from applying a novel equity-specific re-analysis strategy
Authors: Czwikla Gesa , Boen Filip , Cook Derek G. , de Jong Johan , Harris Tess , Hilz Lisa K. , Iliffe Steve , Lechner Lilian , Morris Richard W. , Muellmann Saskia , Peels Denise A. , Pischke Claudia R. , Schüz Benjamin , Stevens Martin , Telkmann Klaus , van Lenthe Frank J. , Vanderlinden Julie , Bolte Gabriele
Published: May 2021

Background

Reducing inequalities in physical activity (PA) and PA-associated health outcomes is a priority for public health. Interventions to promote PA may reduce inequalities, but may also unintentionally increase them. Thus, there is a need to analyze equity-specific intervention effects. However, the potential for analyzing equity-specific effects of PA interventions has not yet been sufficiently exploited. The aim of this study was to set out a novel equity-specific re-analysis strategy tried out in an international interdisciplinary collaboration.

Methods

The re-analysis strategy comprised harmonizing choice and definition of outcomes, exposures, socio-demographic indicators, and statistical analysis strategies across studies, as well as synthesizing results. It was applied in a collaboration of a convenience sample of eight European PA intervention studies in adults aged ≥45 years. Weekly minutes of moderate-to-vigorous PA was harmonized as outcome. Any versus no intervention was harmonized as exposure. Gender, education, income, area deprivation, and marital status were harmonized as socio-demographic indicators. Interactions between the intervention and socio-demographic indicators on moderate-to-vigorous PA were analyzed using multivariable linear regression and random-effects meta-analysis.

Results

The collaborative experience shows that the novel re-analysis strategy can be applied to investigate equity-specific effects of existing PA interventions. Across our convenience sample of studies, no consistent pattern of equity-specific intervention effects was found. Pooled estimates suggested that intervention effects did not differ by gender, education, income, area deprivation, and marital status.

Conclusions

To exploit the potential for equity-specific effect analysis, we encourage future studies to apply the strategy to representative samples of existing study data. Ensuring sufficient representation of ‘hard to reach’ groups such as the most disadvantaged in study samples is of particular importance. This will help to extend the limited evidence required for the design and prioritization of future interventions that are most likely to reduce health inequalities.
CCL21 activation of the MALAT1/SRSF1/mTOR axis underpins the development of gastric carcinoma
Authors: Fu Qianmei , Tan Xiaohong , Tang Huaming , Liu Jijiang
Published: May 2021

Background

As a significant cause of malignancy mortality, gastric carcinoma (GC) has been well documented to be an often-fatal diagnosis. Despite the limitations of effective therapy, immunotherapy has emerged as a promising therapeutic approach capable of killing cancer cells via the immune system. The current study was conducted to investigate the effect of cytokine C–C motif chemokine ligand 21 (CCL21) on GC progression through the metastasis-associated lung adenocarcinoma transcript 1/serine arginine-rich splicing factor 1/mammalian target of rapamycin (MALAT1/SRSF1/mTOR) axis.

Methods

Bioinformatics analysis was conducted to identify the key genes associated with GC and to subsequently predict their downstream genes. The effect of CCL21, MALAT1, and SRSF1 on the malignant phenotypes and epithelial-mesenchymal transition (EMT) of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo were assessed by expression determination and plasmid transfection. Additionally, RNA pull-down and RNA binding protein immunoprecipitation experiments were performed to determine the MALAT1-microRNA-202-3p (miR-203-3p) interaction and miR-202-3p-SRSF1 interaction followed by the analysis of their effect on the mTOR pathway.

Results

CCL21 was identified as a key GC immune gene. Overexpressed CCL21, MALAT1, and SRSF1 along with poorly expressed miR-202-3p were identified in the GC cells. CCL21 induced the MALAT1 expression in a time- and dose-dependent manner. Functionally, MALAT1 targeted miR-202-3p but upregulated SRSF1 and activated mTOR. Crucially, evidence was obtained indicating that CCL21 promoted both the malignant phenotypes and EMT of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo by increasing the MALAT1-induced upregulation of SRSF1.

Conclusions

Taken together, the key observations of our study provide evidence that CCL21 enhances the progression of GC via the MALAT1/SRSF1/mTOR axis, providing a novel therapeutic target for the treatment of GC.
Multimodal immersive trail making-virtual reality paradigm to study cognitive-motor interactions
Authors: Plotnik Meir , Ben-Gal Oran , Doniger Glen M. , Gottlieb Amihai , Bahat Yotam , Cohen Maya , Kimel-Naor Shani , Zeilig Gabi , Beeri Michal Schnaider
Published: May 2021

Background

Neuropsychological tests of executive function have limited real-world predictive and functional relevance. An emerging solution for this limitation is to adapt the tests for implementation in virtual reality (VR). We thus developed two VR-based versions of the classic Color-Trails Test (CTT), a well-validated pencil-and-paper executive function test assessing sustained (Trails A) and divided (Trails B) attention—one for a large-scale VR system (DOME-CTT) and the other for a portable head-mount display VR system (HMD-CTT). We then evaluated construct validity, test–retest reliability, and age-related discriminant validity of the VR-based versions and explored effects on motor function.

Methods

Healthy adults (n = 147) in three age groups (young: n = 50; middle-aged: n = 80; older: n = 17) participated. All participants were administered the original CTT, some completing the DOME-CTT (14 young, 29 middle-aged) and the rest completing the HMD-CTT. Primary outcomes were Trails A and B completion times (tA, tB). Spatiotemporal characteristics of upper-limb reaching movements during VR test performance were reconstructed from motion capture data. Statistics included correlations and repeated measures analysis of variance.

Results

Construct validity was substantiated by moderate correlations between the’gold standard’ pencil-and-paper CTT and the VR adaptations (DOME-CTT: tA 0.58, tB 0.71; HMD-CTT: tA 0.62, tB 0.69). VR versions showed relatively high test–retest reliability (intraclass correlation; VR: tA 0.60–0.75, tB 0.59–0.89; original: tA 0.75–0.85, tB 0.77–0.80) and discriminant validity (area under the curve; VR: tA 0.70–0.92, tB 0.71–0.92; original: tA 0.73–0.95, tB 0.77–0.95). VR completion times were longer than for the original pencil-and-paper test; completion times were longer with advanced age. Compared with Trails A, Trails B target-to-target VR hand trajectories were characterized by delayed, more erratic acceleration and deceleration, consistent with the greater executive function demands of divided vs. sustained attention; acceleration onset later for older participants.

Conclusions

The present study demonstrates the feasibility and validity of converting a neuropsychological test from two-dimensional pencil-and-paper to three-dimensional VR-based format while preserving core neuropsychological task features. Findings on the spatiotemporal morphology of motor planning/execution during the cognitive tasks may lead to multimodal analysis methods that enrich the ecological validity of VR-based neuropsychological testing, representing a novel paradigm for studying cognitive-motor interactions.
Comparison of SARS-CoV-2 indirect and direct RT-qPCR detection methods
Authors: Pearson Joel D. , Trcka Daniel , Lu Suying , Hyduk Sharon J. , Jen Mark , Aynaud Marie-Ming , Hernández J. Javier , Peidis Philippos , Barrios-Rodiles Miriam , Chan Kin , Woodgett Jim , Mazzulli Tony , Attisano Liliana , Pelletier Laurence , Cybulsky Myron I. , Wrana Jeffrey L. , Bremner Rod
Published: May 2021

Background

Sensitive, rapid, and accessible diagnostics continue to be critical to track the COVID-19 pandemic caused by the SARS-CoV-2 virus. RT-qPCR is the gold standard test, and comparison of methodologies and reagents, utilizing patient samples, is important to establish reliable diagnostic pipelines.

Methods

Here, we assessed indirect methods that require RNA extraction with direct RT-qPCR on patient samples. Four different RNA extraction kits (Qiagen, Invitrogen, BGI and Norgen Biotek) were compared. For detection, we assessed two recently developed Taqman-based modules (BGI and Norgen Biotek), a SYBR green-based approach (NEB Luna Universal One-Step Kit) with published and newly-developed primers, and clinical results (Seegene STARMag RNA extraction system and Allplex 2019-nCoV RT-qPCR assay). We also tested and optimized direct, extraction-free detection using these RT-qPCR systems and performed a cost analysis of the different methods evaluated here.

Results

Most RNA isolation procedures performed similarly, and while all RT-qPCR modules effectively detected purified viral RNA, the BGI system provided overall superior performance (lower detection limit, lower Ct values and higher sensitivity), generating comparable results to original clinical diagnostic data, and identifying samples ranging from 65 copies to 2.1 × 105copies of viral genome/μl. However, the BGI detection system is more expensive than other options tested here. With direct RT-qPCR, simply adding an RNase inhibitor greatly improved detection, without the need for any other treatments (e.g. lysis buffers or boiling). The best direct methods detected ~ 10 fold less virus than indirect methods, but this simplified approach reduced sample handling, as well as assay time and cost.

Conclusions

With extracted RNA, the BGI RT-qPCR detection system exhibited superior performance over the Norgen system, matching initial clinical diagnosis with the Seegene Allplex assay. The BGI system was also suitable for direct, extraction-free analysis, providing 78.4% sensitivity. The Norgen system, however, still accurately detected samples with a clinical Ct < 33 from extracted RNA, provided significant cost savings, and was superior to SYBR green assays that exhibited reduced specificity.
Serum levels of miR-21-5p and miR-339-5p associate with occupational trichloroethylene hypersensitivity syndrome
Authors: Liu Wei , Zheng Jian , Ren Xiaohu , Xie Yuxuan , Lin Dafeng , Li Peimao , Lv Yuan , Hoi Maggie Pui Man , Zhang Yanfang , Liu Jianjun
Published: May 2021

Background

Trichloroethylene (TCE) hypersensitivity syndrome (THS) is a dose-independent and potentially life-threatening disease. In this study, we sought to identify THS-related miRNAs and evaluate its potential clinical value.

Methods

Serum samples of five patients and five matched TCE contacts were used for screening differential miRNAs. Another 34 patients and 34 matched TCE contacts were used for verifying significantly differential miRNAs with SYBR™ Green PCR and MGB PCR. The diagnostic model based on these miRNAs was established via the support vector machine (SVM) algorithm. Correlation between differential miRNAs and liver function was analyzed via the Spearman correlation test.

Results

A total of 69 miRNAs was found to be differentially expressed. MiR-21-5p and miR-339-5p were verified to have significant higher expressions in patients. The sensitivity, specificity and accuracy of disease model were 100, 75 and 86%, respectively. The two miRNAs showed significant correlations with liver function.

Conclusion

These findings suggested that miRNAs profiles in serum of THS patients had changed significantly, and miR-21-5p and miR-339-5p were associated with THS.
Determinants of exclusive breastfeeding for the first six months in China: a cross-sectional study
Authors: Shi Huifeng , Yang Yumei , Yin Xiaohan , Li Jia , Fang Jin , Wang Xiaoli
Published: May 2021

Background

Breast milk is the best source of essential nutrients and bioactive components for infants under 6 months. However, little is known about what affects breastfeeding intentions and practices of Chinese mothers. With measures of individual, setting, and sociocultural factors, this study examined determinants of exclusive breastfeeding in the first 6 months of infancy in China.

Methods

Data were obtained from a national cross-sectional survey in China in 2018 that included 5237 infants under 6 months with available measurements of breastfeeding. A 24-h reported food recall method was applied to assess breastfeeding and complementary food intake in the past 24 h. Potential breastfeeding determinants categorized into six aspects were measured: (1) infant health, (2) maternal sociodemographic characteristics, (3) maternal health, (4) breastfeeding support from family, friends, and workplace, (5) social support for breastfeeding, and (6) maternal breastfeeding experiences and knowledge. Reasons for non-commencement or early cessation of breastfeeding were evaluated for non-breastfed infants. For breastfed infants, multivariate logistic regression was used to explore the determinants of exclusive breastfeeding.

Results

About 30 % (29.5%) of infants under 6 months were exclusively breastfed; 2.3% (2.3%) had never been breastfed and 3.2% had ceased breastfeeding. No breast milk (60.7%), maternal illness (13.9%), and infant illness (13.1%) were the top three reasons for non-commencement of breastfeeding. Insufficient breast milk was the reason given for ceasing breastfeeding early by almost two thirds of caregivers who had stopped breastfeeding. The following factors were associated with exclusive breastfeeding: maternal higher education, formal employment with ≥6 months of paid maternity leave, support of the husband and best friends for breastfeeding, a breastfeeding-supportive society, and better breastfeeding knowledge and experiences (a previous successful breastfeeding experience ≥6 months and early initiation of breastfeeding). Maternal age of ≥40 years, caesarean delivery, and infant disease history were associated with non-exclusive breastfeeding.

Conclusions

The exclusive breastfeeding rate is still very low in China. Multidimensional barriers contribute to this situation. A comprehensive intervention framework is needed to increase optimal breastfeeding and achieve substantial public health gains.
HIV testing and its associated factors among street-based female sex workers in Iran: results of a national rapid assessment and response survey
Authors: Ahmadi Sina , Khezri Mehrdad , Roshanfekr Payam , Karimi Salah Eddin , Vameghi Meroe , Ali Delaram , Ahounbar Elahe , Noroozi Mehdi , Shokoohi Mostafa
Published: May 2021

Background

Female sex workers (FSWs) are at a disproportionate risk of sexually transmitted infections and they may face significant barriers to HIV testing. This study aimed to examine HIV testing prevalence and its associated factors among street-based FSWs in Iran.

Method

A total of 898 FSWs were recruited from 414 venues across 19 major cities in Iran between October 2016 and March 2017. Eligible FSWs were women aged 18 years of age who had at least one commercial sexual intercourse in the previous year. HIV testing was defined as having tested for HIV in the lifetime. Bivariable and multivariable logistic regression were used to examine the correlates of HIV testing. We report adjusted odds ratios (aOR) and their 95% confidence intervals (CI).

Result

Overall, 57.8% (95%CI: 20.0, 88.0) of participants reported having tested for HIV, and HIV prevalence among FSWs who tested for HIV was 10.3% (95%CI: 7.5, 13.0). The multivariable model showed that unstable housing (aOR: 8.86, 95%CI: 2.68, 29.32) and drug use (aOR: 3.47, 95%CI: 1.33, 9.06) were associated with increased likelihood of HIV testing. However, FSWs with a higher level of income were less likely to be tested for HIV (aOR: 0.09, 95%CI: 0.02, 0.43).

Conclusion

Almost one in ten street-based FSWs had never tested for HIV. These findings suggest the need for evidence-based strategies such as outreach support and HIV self-testing to improve HIV testing in this marginalized population.
Ostial lesion of the anterior descending coronary artery treated via Szabo technique supported by stent boost imaging: a case report
Authors: Wang Guangliang , Wu Xuemei
Published: May 2021

Background

Stenosis at the opening and bifurcation of the anterior descending branch and circumflex branch around the end of the left main trunk is difficult to repair. Accurate positioning of a stent is the key problem.

Case presentations

Here we report the case of a 61-year-old man who suffered from paroxysmal chest pain for 1 year, without history of diabetes or hypertension. The coronary computed tomography showed mixed plaques in the proximal part of the anterior descending artery, with stenosis severe at 80–90%. The emergency coronary angiography showed occlusion of the anterior descending artery. During percutaneous coronary intervention, a drug-eluting stent was implanted into the anterior descending artery using the Szabo technique, supported by stent boost (StentBoost) imaging to pinpoint the location of the lesion. The patient’s paroxysmal chest pain was relieved after the procedure.

Conclusion

We used StentBoost to verify the accuracy of stent placement and the Szabo technique to rectify long-term coronary stenosis, which achieved satisfactory results. Combining the Szabo technique with StentBoost imaging was helpful to accurately evaluate the area and locate the stent when treating this ostial lesion of the anterior descending coronary artery.
Cdk5 regulatory subunit-associated protein 1 knockout mice show hearing loss phenotypically similar to age-related hearing loss
Authors: Miwa Toru , Wei Fan-yan , Tomizawa Kazuhito
Published: May 2021

Mitochondrial dysfunction is associated with aging and age-related hearing loss (AHL). However, the precise mechanisms underlying the pathophysiology of hearing loss remain unclear. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) enables efficient intramitochondrial translation by catalyzing the deposition of 2-methylthio modifications on mitochondrial tRNAs. Here we investigated the effect of defective mitochondrial protein translation on hearing and AHL in a Cdk5rap1 deficiency C57BL/6 mouse model. Compared to control C57BL/6 mice, Cdk5rap1-knockout female mice displayed hearing loss phenotypically similar to AHL from an early age. The premature hearing loss in Cdk5rap1-knockout mice was associated with the degeneration of the spiral ligament and reduction of endocochlear potentials following the loss of auditory sensory cells. Furthermore, cultured primary mouse embryonic fibroblasts displayed early onset of cellular senescence associated with high oxidative stress and cell death. These results indicate that the CDK5RAP1 deficiency-induced defective mitochondrial translation might cause early hearing loss through the induction of cellular senescence and cochlear dysfunction in the inner ear. Our results suggest that the accumulation of dysfunctional mitochondria might promote AHL progression. Furthermore, our findings suggest that mitochondrial dysfunction and dysregulated mitochondrial tRNA modifications mechanistically cause AHL. Understanding the mechanisms underlying AHL will guide future clinical investigations and interventions in the attempt to mitigate the consequences of AHL.
The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China
Authors: Ni Jing , Cheng Xianzhong , Zhao Qian , Dai Zhiqin , Xu Xia , Guo Wenwen , Gu Hongyuan , Zhou Rui , Wang Yan , Chen Xiaoxiang
Published: May 2021

Background

Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD). We present real-world experience from a single center of China.

Methods

Patients treated with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx®) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity.

Results

Twenty-two patients all received niraparib at a bolus of 200 mg/d. Fifty percent of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI = 0.060–0.759) and disease control rate (DCR) of 50% (95%CI = 0.140–0.861) in the exploratory multi-line monotherapy group. The most common AEs were nausea, thrombocytopenia, and anemia. Grade 3–4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event.

Conclusion

It is feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population can acquire promising efficacy and tolerance. This is the first real-world data about niraparib in ovarian cancer patients with available HRD status from China.
Low prevalence of active trachoma and associated factors among children aged 1–9 years in rural communities of Metema District, Northwest Ethiopia: a community based cross-sectional study
Authors: Ayelgn Kessete , Guadu Tadesse , Getachew Atalay
Published: May 2021

Background

Trachoma is an infectious disease of the eye caused by Chlamydia trachomatis and transmitted via contact with eye discharge from infected persons and leading to blindness worldwide. Children less than 9 years of age affected more seriously. The disease is common where access to water and sanitation are limited.

Objective

To determine the prevalence of active trachoma and associated factors among children aged 1–9 years in rural communities of Metema District, West Gondar Zone, Northwest Ethiopia.

Method

A community based cross-sectional study design was used to collect data from 792 children aged 1–9 years old in Metema district from April to May 2018. Multistage sampling technique was used to select the study participants. Pretested interviewer-administered structured questionnaire and eye examination using binocular loupe to differentiate trachoma cases was the data collection methods and tools. The bivariable and multivariable binary logistic regression model was employed for analysis. P-value < 0.05 was considered to declare statistical significance.

Results

A total of 752 children aged l-9 years were enrolled in this study with response rate of 94.9%. The overall prevalence of active trachoma among the study participants was 11.8% (95% CI, 9.5–13.9). Unprotected source of water (AOR = 4.7; 95% CI: 2.5–8.9), lower household water consumption (AOR = 2.8; 95% CI: 1.3–6.0), improper latrine utilization (AOR = 3.2; 95% CI: 1.5–6.7), and frequency of face washing once per day (AOR = 5.3; 95% CI: 1.2–26.6) were the factors significantly associated with active trachoma.

Conclusion

The current study revealed a lower overall prevalence of active trachoma (11.8%) than the WHO threshold prevalence (20%) used to declare it as a severe public health problem. All residents and health professional should collaborate on trachoma prevention by implementing the WHO SAFE strategy- surgery for trichiasis, antibiotics, facial cleanliness and environmental improvement for further trachoma elimination.
treeclimbR pinpoints the data-dependent resolution of hierarchical hypotheses
Authors: Huang Ruizhu , Soneson Charlotte , Germain Pierre-Luc , Schmidt Thomas S.B. , Mering Christian Von , Robinson Mark D.
Published: May 2021

treeclimbRis for analyzing hierarchical trees of entities, such as phylogenies or cell types, at different resolutions. It proposes multiple candidates that capture the latent signal and pinpoints branches or leaves that contain features of interest, in a data-driven way. It outperforms currently available methods on synthetic data, and we highlight the approach on various applications, including microbiome and microRNA surveys as well as single-cell cytometry and RNA-seq datasets. With the emergence of various multi-resolution genomic datasets,treeclimbRprovides a thorough inspection on entities across resolutions and gives additional flexibility to uncover biological associations.
A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks
Authors: Yuan Chongze , Chen Haojie , Tu Shiqi , Huang Hsin-Yi , Pan Yunjian , Gui Xiuqi , Kuang Muyu , Shen Xuxia , Zheng Qiang , Zhang Yang , Cheng Chao , Hong Hui , Tao Xiaoting , Peng Yizhou , Yao Xingxin , Meng Feilong , Ji Hongbin , Shao Zhen , Sun Yihua
Published: May 2021

Background

Lung adenocarcinoma (LUAD) is a highly malignant and heterogeneous tumor that involves various oncogenic genetic alterations. Epigenetic processes play important roles in lung cancer development. However, the variation in enhancer and super-enhancer landscapes of LUAD patients remains largely unknown. To provide an in-depth understanding of the epigenomic heterogeneity of LUAD, we investigate the H3K27ac histone modification profiles of tumors and adjacent normal lung tissues from 42 LUAD patients and explore the role of epigenetic alterations in LUAD progression.

Results

A high intertumoral epigenetic heterogeneity is observed across the LUAD H3K27ac profiles. We quantitatively model the intertumoral variability of H3K27ac levels at proximal gene promoters and distal enhancers and propose a new epigenetic classification of LUAD patients. Our classification defines two LUAD subgroups which are highly related to histological subtypes. Group II patients have significantly worse prognosis than group I, which is further confirmed in the public TCGA-LUAD cohort. Differential RNA-seq analysis between group I and group II groups reveals that those genes upregulated in group II group tend to promote cell proliferation and induce cell de-differentiation. We construct the gene co-expression networks and identify group-specific core regulators. Most of these core regulators are linked with group-specific regulatory elements, such as super-enhancers. We further show that CLU is regulated by 3 group I-specific core regulators and works as a novel tumor suppressor in LUAD.

Conclusions

Our study systematically characterizes the epigenetic alterations during LUAD progression and provides a new classification model that is helpful for predicting patient prognosis.
Comparison of a fast track protocol and standard care after hip arthroplasty in the reduction of the length of stay and the early weight-bearing resumption: study protocol for a randomized controlled trial
Authors: Rocchi Martina , Stagni Cesare , Govoni Marco , Mazzotta Alessandro , Vivarelli Leonardo , Orlandi Magli Antonella , Perrone Mariada , Benedetti Maria Grazia , Dallari Dante
Published: May 2021

Background

To date, hip arthroplasty is one of the most commonly performed surgical procedures, with growing worldwide demand. In recent decades, major progress made in terms of surgical technique, biomechanics, and tribology knowledge has contributed to improve the medical and functional management of the patient. This study aims to assess if the application of a fast track protocol, consisting of a preoperative educational intervention, adequate postoperative pain control, and intensive rehabilitation intervention, reduces the length of stay (LOS) and allows the early functional recovery compared to standard clinical practice for patients undergoing hip arthroplasty.

Methods

The study population consists of 90 patients with primary arthrosis of the hip with an anterior indication of hip arthroplasty. The exclusion criteria are older than 70 years, a contraindication to performing spinal anesthesia, and bone mass index (BMI) greater than 32. Participants, 45 for each group, are randomly allocated to one of two arms: fast track clinical pathway or standard care protocol. During allocation, baseline parameters such as Harris Hip Score (HHS) and Western Ontario and McMaster Universities (WOMAC) index are collected. On the third postoperative day, the functional autonomy for each patient is assessed by the Iowa Level of Assistance (ILOA) scale, and it is expected the discharge for patients in the fast track group (primary outcome). On the other hand, standard care patient discharge is expected after 5–7 days after surgery. During follow-up fixed at 6 weeks and 3, 6, and 12 months, HHS and WOMAC scores are collected for each patient (secondary outcomes).

Discussion

Although total hip replacement has become a widespread standardized procedure, to the authors’ knowledge, only few randomized controlled trials were performed to evaluate the effectiveness of fast track pathway vs. standard care procedure in the reduction of the LOS after hip arthroplasty. It is expected that our results collected by the application of minimally invasive surgical interventions with concomitant management of perioperative pain and bleeding and early functional rehabilitation will contribute to enriching the understanding of clinical and organizational aspects linked to fast track arthroplasty.

Trial registration

ClinicalTrials.gov NCT03875976. Registered on 15 March 2019—“retrospectively registered”.
Behavioural response of mosquito vectors Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus to synthetic pyrethroid and organophosphorus-based slow-release insecticidal paint
Authors: Dhiman Sunil , Yadav Kavita , Acharya B. N. , Ahirwar Raj Kumar , Sukumaran D.
Published: May 2021

Background

The direct toxicological impact of insecticides on vector mosquitoes has been well emphasized; however, behavioural responses such as excito-repellency and physical avoidance as a result of insecticide exposure have not been much studied. We have demonstrated the excito-repellency and behavioural avoidance in certain vector mosquito species on exposure to a slow-release insecticidal paint (SRIP) formulation in addition to direct toxicity.

Methods

A SRIP formulation developed by the Defence Research and Development Establishment, Gwalior, contains chlorpyriphos, deltamethrin and pyriproxyfen as active insecticides.Anopheles stephensi, Culex quinquefasciatusandAedes aegyptimosquitoes were used to study the excito-repellency response of the formulation. The experiments were performed in a specially designed dual-choice exposure and escape chamber made of transparent polymethyl methacrylate. For the experiments, the SRIP formulation was applied undiluted at a rate of 8 m2per kg on 15 cm2metallic surfaces. Mosquitoes were introduced into the exposure chamber, and observations of the movement of mosquitoes into the escape chamber through the exit portal were taken at 1-min intervals for up to 30 min.

Results

The evaluated formulation displayed strong excito-repellency against all three tested vector mosquito species. Results showed that the ET50(escape time 50%) forAe. aegypti,An. stephensiandCx. quinquefasciatuswas 20.9 min, 14.5 min and 17.9 min for contact exposure (CE) respectively. Altogether in CE, the escape rates were stronger inAn. stephensimosquitoes at different time intervals compared toAe. aegyptiandCx. quinquefasciatusmosquitoes. The probit analysis revealed that the determined ET did not deviate from linearity for both non-contact exposure (NCE) and placebo exposure (PE) (χ2 ≤ 7.9;p = 1.0) forAe. aegyptimosquitoes and for NCE (χ2 = 8.3;p = 1.0) and PE (χ2 = 1.7;p = 1.0) treatments inCx. quinquefasciatus. Mortality (24 h) was found to be statistically higher (F = 6.4;p = 0.02) inAn. stephensifor CE but did not vary for NCE (p ≥ 0.3) and PE (p = 0.6) treatments among the tested mosquito species. Survival probability response suggested that all the three tested species displayed similar survival responses for similar exposures (χ2 ≤ 2.3;p ≥ 0.1).

Conclusion

The study demonstrates the toxicity and strong behavioural avoidance in known vector mosquito species on exposure to an insecticide-based paint formulation. The combination of insecticides in the present formulation will broaden the overall impact spectrum for protecting users from mosquito bites. The efficacy data generated in the study provide crucial information on the effectiveness of the tested formulation and could be useful in reducing the transmission intensity and disease risk in endemic countries.

Graphical Abstract
Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) against natural intestinal nematode infections in dogs presented as veterinary patients in Europe
Authors: Hayes Brad , Wiseman Scott , Snyder Daniel E.
Published: May 2021

Background

A randomised, blinded, positive controlled, multicentre, Good Clinical Practice-compliant, pivotal field study was conducted to evaluate the effectiveness and safety of a new combination of lotilaner + milbemycin oxime tablets (Credelio® Plus; Elanco Animal Health) administered orally to client-owned dogs naturally infected with intestinal nematodes.

Methods

Client-owned dogs presenting to veterinary clinics from households in France, Hungary and Germany were screened for intestinal nematodes. Dogs with an initial positive faecal egg count that was subsequently confirmed with a follow-up faecal examination to demonstrate the presence of naturally occurring mixed or mono-infections with Toxocara canis, Toxascaris leonina, Trichuris vulpis or Ancylostoma caninum were enrolled on Day 0 into the study. Households were randomised in an approximately 2:1 ratio to receive either an investigational product (IP; Credelio Plus tablets) or control product (CP; Nexgard Spectra® tablets) as treatment. Dogs were administered the IP (n = 278) or CP (n = 117) once on Day 0 at a dose rate of 0.75–1.56 mg/kg bodyweight milbemycin oxime and 20.0–41.5 mg/kg bodyweight lotilaner (IP) or as recommended (CP). Effectiveness of the IP and CP treatments was based on the post-treatment reduction in geometric mean faecal egg counts on Day 8 (range Day 7–10) after treatment as compared to their pre-treatment nematode faecal egg counts.

Results

Geometric mean (GM) faecal egg counts for T. canis, A caninum and T. vulpis were reduced by ≥ 97.2% in the Credelio Plus group and  by ≥ 95.3% in the afoxolaner + milbemycin oxime group. There were insufficient data to calculate a percentage reduction in GM faecal egg counts between Day 0 and Day 8 for T. leonina due to low prevalence. Credelio Plus was well tolerated in this field study. Of the 355 total doses administered, 82.3% were accepted free choice in the IP group compared to 80.8% in the CP group.

Conclusions

This study demonstrated effectiveness (≥ 97.2% reduction), safety and tablet acceptance of a combination of milbemycin oxime and lotilaner (Credelio Plus) administered orally to dogs with natural intestinal infections of T. canis, A. caninum and T. vulpis.

Graphical Abstract