bluuebunny/crossref_metadata_2025 huggingface dataset:
Human seminal virome: a panel based on recent literature
Authors: de Albuquerque Beatriz Helena Dantas Rodrigues , de Oliveira Maryana Thalyta Ferreira Camara , Aderaldo Janaína Ferreira , de Medeiros Garcia Torres Mychelle , Lanza Daniel Carlos Ferreira
Published: August 2022

Background

The seminal virome and its implications for fertility remain poorly understood. To date, there are no defined panels for the detection of viruses of clinical interest in seminal samples.

Results

In this study, we characterized the human seminal virome based on more than 1,000 studies published over the last five years.

Conclusions

The number of studies investigating viruses that occur in human semen has increased, and to date, these studies have been mostly prospective or related to specific clinical findings. Through the joint analysis of all these studies, we have listed the viruses related to the worsening of seminal parameters and propose a new panel with the main viruses already described that possibly affect male fertility and health. This panel can assist in evaluating semen quality and serve as a tool for investigation in cases of infertility.
Misdiagnosis of vasitis: a potential diagnostic pitfall with computed tomography
Authors: Li Yi Hong , Huang Zhon min , Yu Ji kuen , Lin Yi Sheng , Hsu Chao Yu , Tung Min Che
Published: August 2022

Background

Vasitis is a rare condition that may be challenging for the clinical practitioner. Sometimes it is misdiagnosed as incarcerated inguinal hernia; thus, patients end up receiving unnecessary surgery. Compared with the traditional approach with only sonography, the more recent introduction of computed tomography in the diagnostic process has provided higher quality imaging and more detailed anatomy. Consequently, some urologists advocate the efficacy of computed tomography in the differential diagnosis of difficult cases.

Case presentation

We present the case of a 23-year-old male who suffered from right inguinal pain and swelling. His scrotum ultrasound showed multiple tubular structure dilatation within the subinguinal area and no testis torsion. The initial diagnosis was a right inguinal hernia. Computed tomography supported that initial diagnosis, and we presumed the lesion represented a herniation of the omentum with mesenteric vessels. Since there was a suspicion of hernia incarceration, the patient underwent diagnostic laparoscopy, which did not reveal herniation, but only erythematous reaction and swelling over the right spermatic cord. Following a final diagnosis of vasitis, he received empirical antibiotic treatment and his symptoms entirely resolved.

Conclusions

Even though computed tomography can provide thorough imaging of the urogenital system, the contrast enhancement within vessels and inflammatory organs can still be misleading in the diagnostic process.
SCONCE2: jointly inferring single cell copy number profiles and tumor evolutionary distances
Authors: Hui Sandra , Nielsen Rasmus
Published: August 2022

Background

Single cell whole genome tumor sequencing can yield novel insights into the evolutionary history of somatic copy number alterations. Existing single cell copy number calling methods do not explicitly model the shared evolutionary process of multiple cells, and generally analyze cells independently. Additionally, existing methods for estimating tumor cell phylogenies using copy number profiles are sensitive to profile estimation errors.

Results

We present SCONCE2, a method for jointly calling copy number alterations and estimating pairwise distances for single cell sequencing data. Using simulations, we show that SCONCE2 has higher accuracy in copy number calling and phylogeny estimation than competing methods. We apply SCONCE2 to previously published single cell sequencing data to illustrate the utility of the method.

Conclusions

SCONCE2 jointly estimates copy number profiles and a distance metric for inferring tumor phylogenies in single cell whole genome tumor sequencing across multiple cells, enabling deeper understandings of tumor evolution.
Physical activity as a risk or protective factor for falls and fall-related fractures in non-frail and frail older adults: a longitudinal study
Authors: van Gameren Maaike , Hoogendijk Emiel O. , van Schoor Natasja M. , Bossen Daniël , Visser Bart , Bosmans Judith E. , Pijnappels Mirjam
Published: August 2022

Background

Physical activity may be both a risk and protective factor for falls and fall-related fractures. Despite its positive effects on muscle and bone health, physical activity also increases exposure to situations where falls and fractures occur. This paradox could possibly be explained by frailty status. Therefore, the aim of this study was to investigate the associations between physical activity and both falls and fractures, and to determine whether frailty modifies the association of physical activity with falls, and fractures.

Methods

Data of 311 community-dwelling participants aged 75 years or older from the Longitudinal Aging Study Amsterdam, who participated in a three-year longitudinal study with five nine-monthly measurements between 2015/2016 and 2018/2019. Their mean age was 81.1 (SD 4.8) years and frailty was present in 30.9% of the participants. Physical activity in minutes per day was objectively assessed with an inertial sensor (Actigraph) for seven consecutive days. Falls and fractures were assessed every nine months using self-report during an interview over a follow-up period of three years. Frailty was determined at baseline using the frailty index. Associations were estimated using longitudinal logistic regression analyses based on generalized estimating equations.

Results

No association between physical activity and falls was found (OR = 1.00, 95% CI: 0.99–1.00). Fall risk was higher in frail compared to non-frail adults (OR = 2.21, 95% CI: 1.33–3.68), but no effect modification was seen of frailty on the association between physical activity and falls. Also no relation between physical activity and fractures was found (OR = 1.00, 95% CI: 0.99–1.01). Fracture risk was higher in frail compared to non-frail adults (OR = 2.81, 95% CI: 1.02–7.75), but also no effect modification of frailty was present in the association between physical activity and fractures.

Conclusions

No association between physical activity and neither falls nor fractures was found, and frailty appeared not to be an effect modifier. However, frailty was a risk factor for falls and fractures in this population of older adults. Our findings suggest that physical activity can be safely recommended in non-frail and frail populations for general health benefits, without increasing the risk of falls.
Lower grip strength and insufficient physical activity can increase depressive symptoms among middle-aged and older European adults: a longitudinal study
Authors: Zheng Han , He Qingwen , Xu Hongyan , Zheng Xiaowei , Gu Yanfang
Published: August 2022

Objectives

The present study aimed to identify the gender-specific trajectories of grip strength using group-based trajectories, explore the interaction between grip strength and physical activity on depression, and investigate the association of physical activity with the change in depression by different grip strength groups among middle-aged and older European adults.

Methods

A total of 14,098 participants aged 50 years or older from the Survey of Health, Ageing and Retirement in Europe 2007–2019 were included in this study. Group-based trajectory modeling was used to identify the low, middle and high group of grip strength by gender. Generalized estimated equations were fitted to analyze the interaction effect. The data of wave 2-wave 5 and wave 2-wave 7 were chosen to conduct sensitivity analyses.

Results

Significant interactions between grip strength group and physical inactivity were found (x2interaction = 11.16, P = 0.004). Significant interactions between physical inactivity and time on depression were identified in low (x2interaction = 27.83, P < 0.001) and moderate (x2interaction = 23.67, P < 0.001) grip strength, but a similar result was not found in high grip strength (x2interaction = 4.39, P = 0.495). Participants in the physical inactivity group had higher depression scores in the low and moderate grip strength groups. Sensitivity analyses yield almost similar results.

Conclusions

Grip strength and physical inactivity interact with depression. Lower grip strength and insufficient physical activity can increase depressive symptoms. People with lower grip strength and physical inactivity should pay special attention to the prevention of depression.
Psychoeducational group intervention for intellectually able adults with autism and their close relations (Prisma) – an open feasibility study
Authors: Hidalgo Nathaniel , Sjöwall Douglas , Agius Hanna , Byström Caroline , Brar Annika , Borg Jacqueline , Hirvikoski Tatja
Published: August 2022

Background

Autism spectrum disorder (ASD) in adulthood is associated with severe impairments in functioning and poor health, while ASD is also affecting close relations. Accessible first-line interventions addressing the complex clinical needs and care coordination are lacking.

Methods

This study investigated the feasibility and preliminary effects of a new psychoeducational intervention (Prisma) developed for intellectually able adults with ASD and their close relations in an outpatient setting. The manualized Prisma intervention consist of four weekly group sessions guided by trained group leaders and providing information about autism, support, and services. Feasibility was examined through treatment completion rate and group-level comparisons between intervention completers and non-completers (Student’s t-test, Fisher’s exact test, and Pearson’s chi-squared test). Perceived treatment credibility was investigated by within-group comparisons of participant’s self-ratings from pre-intervention to post-intervention, as well as by group leaders’ ratings using an adjusted questionnaire. Treatment satisfaction was examined quantitatively regarding the session evaluations (Student’s t-tests), as well as by a qualitative thematic analysis of participants’ feedback. Preliminary efficacy was studied using paired t-tests (pre- and post-intervention).

Results

Completion rate was 77% (n = 71 of the 92 adults with ASD) and 73% (n = 69 of the 94 close relations), respectively. Participants considered Prisma to be an acceptable intervention indicated by increases in treatment credibility and expectations from pre- to post-intervention. The group leaders reported treatment credibility in the same range as the participants. Both autistic adults and their close relations reported good treatment satisfaction for each session, while the qualitative thematic analysis indicated that Prisma could be improved by enhancing active participation. This participant feedback will be used to further improve the intervention for an upcoming RCT. Preliminary analyses of effects showed promising results with an increase in knowledge of ASD and some indications for improvements in relationship quality, mental health, quality of life, acceptance of diagnosis and burden of care.

Conclusions

Overall, results indicate that the Prisma is a feasible and acceptable first-line intervention in outpatient services. Randomized controlled trials are needed to further corroborate the evidence base of this novel intervention.

Trial registration

Clinicaltrials.org NCT0446097, retrospectively registered July 8th 2020.
RPS6KA5 methylation predict response to 6-week treatment for adolescent MDD patients
Authors: Xu Peiwei , Tao Yuanmei , Zhang Hang , Jin Meijiang , Xu Hanmei , Zou Shoukang , Deng Fang , Huang Lijuan , Zhang Hong , Wang Xiaolan , Tang Xiaowei , Dong Zaiquan , Wang Yanping , Yin Li , Sun Xueli
Published: August 2022

Objective

We aimed to investigate the effect of differentially methylated genes and chronic childhood stress on the development of depressive symptoms in Chinese adolescents, as well as to test whether methylation at baseline can be used as a predictor of remission at follow-up after six weeks of treatment.

Methods

After recruiting 87 MDD patients and 53 healthy controls, we compared demographic and baseline clinical characteristics. The Childhood Chronic Stress Questionnaire was used to assess stress caused by early-life events. MDD patients underwent six weeks of treatment, and response to treatment was assessed using the Beck Depression Inventory-II. In addition, four MDD patients and five controls were randomly chosen for genome-wide methylation analysis.

Results

The gene RPS6KA5 showed significant methylation differences between the two groups. Severity of chronic childhood stress was significantly associated with increased risk of depression in adolescents, but not with treatment response. Baseline RPS6KA5 methylation can predict remission after six weeks of treatment. We did not observe any interaction between RPS6KA5 methylation and chronic childhood stress.

Conclusions

Our results suggest that RPS6KA5 methylation can be used as a predictor of response to treatment in adolescent MDD patients. Here we offer new evidence for the role of epigenetics in early response to treatment of depression.

Trial registration

ChiCTR, ChiCTR2000033402, 31/05/2020, http://www.chictr.org.cn/index.aspx
Pilot study of the DART tool - an objective healthcare simulation debriefing assessment instrument
Authors: Baliga Kaushik , Coggins Andrew , Warburton Sandra , Mathias Divya , Yamada Nicole K. , Fuerch Janene H. , Halamek Louis P.
Published: August 2022

Background

Various rating tools aim to assess simulation debriefing quality, but their use may be limited by complexity and subjectivity. The Debriefing Assessment in Real Time (DART) tool represents an alternative debriefing aid that uses quantitative measures to estimate quality and requires minimal training to use. The DART is uses a cumulative tally of instructor questions (IQ), instructor statements (IS) and trainee responses (TR). Ratios for IQ:IS and TR:[IQ + IS] may estimate the level of debriefer inclusivity and participant engagement.

Methods

Experienced faculty from four geographically disparate university-affiliated simulation centers rated video-based debriefings and a transcript using the DART. The primary endpoint was an assessment of the estimated reliability of the tool. The small sample size confined analysis to descriptive statistics and coefficient of variations (CV%) as an estimate of reliability.

Results

Ratings for Video A (n = 7), Video B (n = 6), and Transcript A (n = 6) demonstrated mean CV% for IQ (27.8%), IS (39.5%), TR (34.8%), IQ:IS (40.8%), and TR:[IQ + IS] (28.0%). Higher CV% observed in IS and TR may be attributable to rater characterizations of longer contributions as either lumped or split. Lower variances in IQ and TR:[IQ + IS] suggest overall consistency regardless of scores being lumped or split.

Conclusion

The DART tool appears to be reliable for the recording of data which may be useful for informing feedback to debriefers. Future studies should assess reliability in a wider pool of debriefings and examine potential uses in faculty development.
A nationwide registry for recurrent urolithiasis in the upper urinary tract – The RECUR study protocol
Authors: Schoenthaler Martin , Fichtner Urs Alexander , Boeker Martin , Zoeller Daniela , Binder Harald , Prokosch Hans-Ulrich , Praus Friederike , Walther Tabea , Glienke Maximilian , Horki Petar , Gratzke Christian , Farin-Glattacker Erik
Published: August 2022

Background

Urinary stone disease is a widespread disease with tremendous impact on those affected and on societies around the globe. Nevertheless, clinical and health care research in this area seem to lag far behind cardiovascular diseases or cancer. This may be due to the lack of an immediate deadly threat from the disease and therefore less public and professional interest. However, the patients suffer from recurring, sometimes intense pain and often must be treated in hospital. Long-term morbidity includes doubled rates of chronic kidney disease and arterial hypertension after at least one stone-related event. Observational studies, more specifically, registries and other electronic data sets have been proposed as a means of filling critical gaps in evidence. We propose a nationwide digital and fully automated registry as part of the German Ministry for Education and Research (BMBF) call for the "establishment of model registries”.

Methods

RECUR builds on the technical infrastructure of Germany’s Medical Informatics Initiative. Local data integration centres (DIC) of participating medical universities will collect pseudonymized and harmonized data from respective hospital information systems. In addition to their clinical data, participants will provide patient reported outcomes using a mobile patient app. Scientific data exploration includes queries and analysis of federated data from DICs of eleven participating sites. All primary patient data will remain at the participating sites at all times. With comprehensive data from this longitudinal registry, we will be able to describe the disease burden, to determine and validate risk factors, and to evaluate treatments. Implementation and operation of the RECUR registry will be funded by the BMBF for five years. Subsequently, the registry is to be continued by the German Society of Urology without significant costs for study personnel.

Discussion

The proposed registry will substantially improve the structural and procedural framework for patients with recurrent urolithiasis. This includes advanced diagnostic algorithms and treatment pathways. The registry will help us identify those patients who will most benefit from specific interventions to prevent recurrences. The RECUR study protocol and the registry’s technical architecture including full digitalization and automation of almost all registry-associated proceedings can be transferred to future registries.

Trial registration

This study is registered at the German Clinical Trial Register (Deutsches Register Klinischer Studien), DRKS-ID DRKS00026923, date of registration January, 11th 2022.
Modelling vaccination capacity at mass vaccination hubs and general practice clinics: a simulation study
Authors: Hanly Mark , Churches Tim , Fitzgerald Oisín , Caterson Ian , MacIntyre Chandini Raina , Jorm Louisa
Published: August 2022

Background

COVID-19 mass vaccination programs place an additional burden on healthcare services. We aim to model the queueing process at vaccination sites to inform service delivery.

Methods

We use stochastic queue network models to simulate queue dynamics in larger mass vaccination hubs and smaller general practice (GP) clinics. We estimate waiting times and daily capacity based on a range of assumptions about appointment schedules, service times and staffing and stress-test these models to assess the impact of increased demand and staff shortages. We also provide an interactive applet, allowing users to explore vaccine administration under their own assumptions.

Results

Based on our assumed service times, the daily throughput for an eight-hour clinic at a mass vaccination hub ranged from 500 doses for a small hub to 1400 doses for a large hub. For GP clinics, the estimated daily throughput ranged from about 100 doses for a small practice to almost 300 doses for a large practice. What-if scenario analysis showed that sites with higher staff numbers were more robust to system pressures and mass vaccination sites were more robust than GP clinics.

Conclusions

With the requirement for ongoing COVID-19 booster shots, mass vaccination is likely to be a continuing feature of healthcare delivery. Different vaccine sites are useful for reaching different populations and maximising coverage. Stochastic queue networks offer a flexible and computationally efficient approach to simulate vaccination queues and estimate waiting times and daily throughput to inform service delivery.
Modulation of macrophage inflammatory function through selective inhibition of the epigenetic reader protein SP140
Authors: Ghiboub Mohammed , Koster Jan , Craggs Peter D. , Li Yim Andrew Y. F. , Shillings Anthony , Hutchinson Sue , Bingham Ryan P. , Gatfield Kelly , Hageman Ishtu L. , Yao Gang , O’Keefe Heather P. , Coffin Aaron , Patel Amish , Sloan Lisa A. , Mitchell Darren J. , Hayhow Thomas G. , Lunven Laurent , Watson Robert J. , Blunt Christopher E. , Harrison Lee A. , Bruton Gordon , Kumar Umesh , Hamer Natalie , Spaull John R. , Zwijnenburg Danny A. , Welting Olaf , Hakvoort Theodorus B. M. , te Velde Anje A. , van Limbergen Johan , Henneman Peter , Prinjha Rab K. , de Winther Menno P. J. , Harker Nicola R. , Tough David F. , de Jonge Wouter J.
Published: August 2022

Background

SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn’s disease (CD), suggesting a role in inflammation.

Results

We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 function in macrophages. We show that SP140 is highly expressed in CD mucosal macrophages and in in vitro-generated inflammatory macrophages. SP140 inhibition through GSK761 reduced monocyte-to-inflammatory macrophage differentiation and lipopolysaccharide (LPS)-induced inflammatory activation, while inducing the generation of CD206+ regulatory macrophages that were shown to associate with a therapeutic response to anti-TNF in CD patients. SP140 preferentially occupies transcriptional start sites in inflammatory macrophages, with enrichment at gene loci encoding pro-inflammatory cytokines/chemokines and inflammatory pathways. GSK761 specifically reduces SP140 chromatin binding and thereby expression of SP140-regulated genes. GSK761 inhibits the expression of cytokines, including TNF, by CD14+ macrophages isolated from CD intestinal mucosa.

Conclusions

This study identifies SP140 as a druggable epigenetic therapeutic target for CD.
Time-resolved trajectory of glucose lowering medications and cardiovascular outcomes in type 2 diabetes: a recurrent neural network analysis
Authors: Longato Enrico , Di Camillo Barbara , Sparacino Giovanni , Avogaro Angelo , Fadini Gian Paolo
Published: August 2022

Aim

Treatment algorithms define lines of glucose lowering medications (GLM) for the management of type 2 diabetes (T2D), but whether therapeutic trajectories are associated with major adverse cardiovascular events (MACE) is unclear. We explored whether the temporal resolution of GLM usage discriminates patients who experienced a 4P-MACE (heart failure, myocardial infarction, stroke, death for all causes).

Methods

We used an administrative database (Veneto region, North-East Italy, 2011–2018) and implemented recurrent neural networks (RNN) with outcome-specific attention maps. The model input included age, sex, diabetes duration, and a matrix of GLM pattern before the 4P-MACE or censoring. Model output was discrimination, reported as area under receiver characteristic curve (AUROC). Attention maps were produced to show medications whose time-resolved trajectories were the most important for discrimination.

Results

The analysis was conducted on 147,135 patients for training and model selection and on 10,000 patients for validation. Collected data spanned a period of ~ 6 years. The RNN model efficiently discriminated temporal patterns of GLM ending in a 4P-MACE vs. those ending in an event-free censoring with an AUROC of 0.911 (95% C.I. 0.904–0.919). This excellent performance was significantly better than that of other models not incorporating time-resolved GLM trajectories: (i) a logistic regression on the bag-of-words encoding all GLM ever taken by the patient (AUROC 0.754; 95% C.I. 0.743–0.765); (ii) a model including the sequence of GLM without temporal relationships (AUROC 0.749; 95% C.I. 0.737–0.761); (iii) a RNN model with the same construction rules but including a time-inverted or randomised order of GLM. Attention maps identified the time-resolved pattern of most common first-line (metformin), second-line (sulphonylureas) GLM, and insulin (glargine) as those determining discrimination capacity.

Conclusions

The time-resolved pattern of GLM use identified patients with subsequent cardiovascular events better than the mere list or sequence of prescribed GLM. Thus, a patient’s therapeutic trajectory could determine disease outcomes.
Circular RNA circFIRRE drives osteosarcoma progression and metastasis through tumorigenic-angiogenic coupling
Authors: Yu Lingfeng , Zhu Hao , Wang Zhen , Huang Jianhao , Zhu Yan , Fan Gentao , Wang Yicun , Chen Xi , Zhou Guangxin
Published: August 2022

Background

Disappointing clinical efficacy of standard treatment has been proven in refractory metastatic osteosarcoma, and the emerging anti-angiogenic regimens are still in the infantile stage. Thus, there is an urgent need to develop novel therapeutic approach for osteosarcoma lung metastasis.

Methods

circFIRRE was selected from RNA-sequencing of 4 matched osteosarcoma and adjacent samples. The expression of circFIRRE was verified in clinical osteosarcoma samples and cell lines via quantitative real-time polymerase chain reaction (RT-qPCR). The effect of circFIRRE was investigated in cell lines in vitro models, ex vivo models and in vivo xenograft tumor models, including proliferation, invasion, migration, metastasis and angiogenesis. Signaling regulatory mechanism was evaluated by RT-qPCR, Western blot, RNA pull-down and dual-luciferase reporter assays.

Results

In this article, a novel circular RNA, circFIRRE (hsa_circ_0001944) was screened out and identified from RNA-sequencing, and was upregulated in both osteosarcoma cell lines and tissues. Clinically, aberrantly upregulated circFIRRE portended higher metastatic risk and worse prognosis in osteosarcoma patients. Functionally, in vitro, ex vivo and in vivo experiments demonstrated that circFIRRE could drive primary osteosarcoma progression and lung metastasis by inducing both tumor cells and blood vessels, we call as “tumorigenic-angiogenic coupling”. Mechanistically, upregulated circFIRRE was induced by transcription factor YY1, and partially boosted the mRNA and protein level of LUZP1 by sponging miR-486-3p and miR-1225-5p.

Conclusions

We identified circFIRRE as a master regulator in the tumorigenesis and angiogenesis of osteosarcoma, which could be purposed as a novel prognostic biomarker and therapeutic target for refractory osteosarcoma.
Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/β-catenin signaling to promote colorectal cancer progression by preventing m6A-mediated degradation of STEAP3 mRNA
Authors: Zhou Li , Jiang Jingwen , Huang Zhao , Jin Ping , Peng Liyuan , Luo Maochao , Zhang Zhe , Chen Yan , Xie Na , Gao Wei , Nice Edouard C. , Li Jing-Quan , Chen Hai-Ning , Huang Canhua
Published: August 2022

Background

Hypoxia, a typical hallmark of solid tumors, exhibits an essential role in the progression of colorectal cancer (CRC), in which the dysregulation of long non-coding RNAs (lncRNAs) is frequently observed. However, the underlying mechanisms are not clearly defined.

Methods

The TCGA database was analyzed to identify differential lncRNA expression involved in hypoxia-induced CRC progression. qRT-PCR was conducted to validate the upregulation of lncRNASTEAP3-AS1in CRC cell lines and tumor-bearing mouse and zebrafish models under hypoxia. ChIP-qRT-PCR was used to detect the transcriptional activation ofSTEAP3-AS1mediated by HIF-1α. RNA-seq, fluorescent in situ hybridization, RNA pulldown, RNA immunoprecipitation, co-immunoprecipitation, immunofluorescence and immunoblot experiments were used to ascertain the involved mechanisms. Functional assays were performed in both in vitro and in vivo models to investigate the regulatory role ofSTEAP3-AS1/STEAP3/Wnt/β-catenin axis in CRC proliferation and metastasis.

Results

Here, we identified a hypoxia-induced antisense lncRNASTEAP3-AS1that was highly expressed in clinical CRC tissues and positively correlated with poor prognosis of CRC patients. Upregulation of lncRNASTEAP3-AS1, which was induced by HIF-1α-mediated transcriptional activation, facilitated the proliferation and metastasis of CRC cells both in vitro and in vivo. Mechanistically,STEAP3-AS1interacted competitively with the YTH domain-containing family protein 2 (YTHDF2), a N6-methyladenosine (m6A) reader, leading to the disassociation of YTHDF2 withSTEAP3mRNA. This effect protectedSTEAP3mRNA from m6A-mediated degradation, enabling the high expression of STEAP3 protein and subsequent production of cellular ferrous iron (Fe2+). Increased Fe2+levels elevated Ser 9 phosphorylation of glycogen synthase kinase 3 beta (GSK3β) and inhibited its kinase activity, thus releasing β-catenin for nuclear translocation and subsequent activation of Wnt signaling to support CRC progression.

Conclusions

Taken together, our study highlights the mechanisms of lncRNASTEAP3-AS1in facilitating CRC progression involving theSTEAP3-AS1/STEAP3/Wnt/β-catenin axis, which may provide novel diagnostic biomarkers or therapeutic targets to benefit CRC treatment.

Graphical abstract

Hypoxia-induced HIF-1α transcriptionally upregulates the expression of lncRNASTEAP3-AS1, which interacts competitively with YTHDF2, thus upregulating mRNA stability ofSTEAP3and consequent STEAP3 protein expression. The enhanced STEAP3 expression results in production of cellular ferrous iron (Fe2+), which induces the Ser 9 phosphorylation and inactivation of GSK3β, releasing β-catenin for nuclear translocation and contributing to subsequent activation of Wnt signaling to promote CRC progression.
A randomized double blind comparison of atosiban in patients with recurrent implantation failure undergoing IVF treatment
Authors: Tang Chuan Ling , Li Qi Yue , Chen Feng Lian , Cai Chen Ting , Dong Yue Yan , Wu Yuan Yuan , Yang Jian Zhi , Zhao Mei , Chi Feng Li , Hong Ling , Ai Ai , Chen Miao Xin , Li Kun Ming , Teng Xiao Ming , Chen Zhi Qin
Published: August 2022

Background

Patients with recurrent implantation failure (RIF) may have more uterine contractions. Several observational studies suggested that atosiban administration around embryo transfer resulted in higher pregnancy rates in RIF patients. This study aimed to evaluate the effect of atosiban given before fresh embryo transfer on pregnancy outcomes of women with RIF.

Methods

A prospective, randomized, double-blind controlled clinical trial was performed in IVF center of Shanghai First Maternity and Infant Hospital. According to a computer-generated randomization list, 194 infertile women with RIF received fresh embryo transfer between July 2017 and December 2019 were randomly allocated into the atosiban (n = 97) and the placebo (n = 97) groups. Women in the treatment group received atosiban intravenously about 30 min before embryo transfer with a bolus dose of 6.75 mg over one minute. Those in the placebo group received only normal saline infusion for the same duration.

Results

There was no significant difference in the live birth rate between the atosiban and placebo groups (42.3% vs 35.1%, P = 0.302, RR = 1.206 (0.844–1.723)). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and implantation rates. Similar results were found when stratified by the number of embryos previously transferred, number of previous failed embryo transfers, frequency of endometrial peristalsis on embryo transfer day (≥ 3 waves/min) or serum estradiol (E2) on the day of hCG above the median level. And, there was no correlation between the serum E2 level on the day of hCG and the frequency of endometrial peristalsis on embryo transfer day. The frequency of endometrial peristalsis on embryo transfer day, total FSH/HMG dosage and duration were the significant factors which independently predicted the likelihood of a live birth.

Conclusions

These results suggested that atosiban treatment before fresh embryo transfer might not improve the live birth rate in RIF patients.

Trial registration

The study had been approved by the Institutional Review Board of the hospital (2017 ethics No.43) and was registered under Clinicaltrials.gov with an identifier NCT02893722.
Deconstructing design thinking as a tool for the implementation of a population health initiative
Authors: Jarrett Caitlin , Baxter Yara C. , Boch Johannes , Carrasco Conrado , Cobos Muñoz Daniel , Mauro Dib Karina , Pessoa Lara , Saric Jasmina , Silveira Mariana , Steinmann Peter
Published: August 2022

Background

The translation of evidence-based practices and rapid uptake of innovations into global health practice is challenging. Design thinking is a consultative process involving multiple stakeholders and has been identified as a promising solution to create and apply implementation strategies in complex environments like health systems.

Methods

We conducted a process evaluation of a real-world example, namely an initiative to innovate hypertension screening, diagnosis and care in São Paulo, Brazil. The parameters of the evaluation were informed by a specification rubric and categorization system, recommended for the investigation of implementation strategies, and the double-diamond conceptual framework to describe and examine the strategic architecture and nature of the design thinking approach, with particular emphasis on identifying potential areas of “value-add” particular to the approach. The retrospective evaluation was performed by an independent partner who had not been involved in the setting up and implementation of the design thinking process.

Results

The evaluation unveiled a dense catalogue of strategically driven, mostly theoretically based, activities involving all identified health system stakeholders including patients. Narrative reconstruction illuminated the systematic and coherent nature of this approach, with different resulting actions progressively accounting for all relevant layers of the health system to engineer a broad selection of specific implementation solutions. The relevance of the identified features and the mechanics used to promote more successful implementation practices was manifested in several distinct ways: design thinking offered a clear direction on which innovations really mattered and when, as well as several new dimensions for consideration in the development of an innovation mindset amongst stakeholders. It thereby promoted relationship quality in terms of familiarity and trust, and commitment to evidence-based enquiry and action. Design thinking was also able to navigate the territory between the need for intervention “fidelity” versus “adaptation” and provide the operational know-how to face familiar implementation hurdles. Lastly, it brought a new kind of skill set to the public health stakeholders that incorporated diplomacy, multidisciplinary approaches and management sciences—skills that are considered necessary but not yet widely taught as part of public health training.

Conclusions

Design thinking is a sound and viable tool to use as part of an implementation strategy for engaging with health system stakeholders and successfully translating evidence-based practices and new innovations into routine practice, thereby addressing an important knowledge—practice gap and, more broadly, contributing to the strategic repertoire available to implementation science.
Preoperative computed tomography-guided localization for multiple pulmonary nodules: comparison of methylene blue and coil
Authors: Zhang Sheng-Feng , Liu Hai-Ri , Ma Ai-Li , Li Er-Liang
Published: August 2022

Background

Preoperative computed tomography (CT)-guided localization has been used to guide the video-assisted thoracoscopic surgery (VATS) sublobar (wedge or segmental) resection for pulmonary nodules (PNs). We aimed to assess the relative efficacy and safety of CT-guided methylene blue (MB)- and coil-based approaches to the preoperative localization of multiple PNs (MPNs).

Methods

Between January 2015 and December 2020, 31 total cases suffering from MPNs at our hospital underwent CT-guided localization and subsequent VATS resection in our hospital, of whom 15 and 16 respectively underwent MB localization (MBL) and coil localization (CL). The clinical effectiveness and complication rates were compared between 2 groups.

Results

The PN- and patient-based technical success rates in the MBL group were both 100%, whereas in the CL group they were 97.2% (35/36) and 93.8% (15/16), respectively, with no substantial discrepancies between groups. Patients in the MBL group illustrated a substantially shorter CT-guided localization duration compared with the CL group (18 min vs. 29.5 min, P < 0.001). Pneumothorax rates (P = 1.000) and lung hemorrhage (P = 1.000) were comparable in both groups. In the MBL and CL groups, the median interval between localization and VATS was 1 h and 15.5 h, respectively (P < 0.001). One-stage VATS sublobar resection of the target nodules was successfully performed in all patients from both groups.

Conclusion

Both CT-guided MBL and CL can be readily and safely utilized for preoperative localization in individuals who had MPNs, with MBL being correlated with a shorter localization duration compared with CL.
Comparative transcriptome in large-scale human and cattle populations
Authors: Yao Yuelin , Liu Shuli , Xia Charley , Gao Yahui , Pan Zhangyuan , Canela-Xandri Oriol , Khamseh Ava , Rawlik Konrad , Wang Sheng , Li Bingjie , Zhang Yi , Pairo-Castineira Erola , D’Mellow Kenton , Li Xiujin , Yan Ze , Li Cong-jun , Yu Ying , Zhang Shengli , Ma Li , Cole John B. , Ross Pablo J. , Zhou Huaijun , Haley Chris , Liu George E. , Fang Lingzhao , Tenesa Albert
Published: August 2022

Background

Cross-species comparison of transcriptomes is important for elucidating evolutionary molecular mechanisms underpinning phenotypic variation between and within species, yet to date it has been essentially limited to model organisms with relatively small sample sizes.

Results

Here, we systematically analyze and compare 10,830 and 4866 publicly available RNA-seq samples in humans and cattle, respectively, representing 20 common tissues. Focusing on 17,315 orthologous genes, we demonstrate that mean/median gene expression, inter-individual variation of expression, expression quantitative trait loci, and gene co-expression networks are generally conserved between humans and cattle. By examining large-scale genome-wide association studies for 46 human traits (average n = 327,973) and 45 cattle traits (average n = 24,635), we reveal that the heritability of complex traits in both species is significantly more enriched in transcriptionally conserved than diverged genes across tissues.

Conclusions

In summary, our study provides a comprehensive comparison of transcriptomes between humans and cattle, which might help decipher the genetic and evolutionary basis of complex traits in both species.
Canine nematode and Giardia spp. infections in dogs in Edmonton, Alberta, the “CANIDA” study
Authors: Visscher Darcy , Porter Emilie , Sweet Sarah , Szlosek Donald , Horr Stephanie
Published: August 2022

Background

Canine intestinal parasite prevalence may be influenced by geographical region, age, and health status of the dog. Behaviors such as predation, scavenging, or roaming as well as routine administration of anthelmintics also play a role. The purpose of this study was to evaluate fecal test results using zinc sulfate flotation by centrifugation combined with coproantigen testing directed at protein antigens excreted or secreted by hookworms (Ancylostoma spp. Uncinaria stenocephala), ascarids (Toxocara canis, Toxascaris spp. Baylisascaris spp.), whipworms (Trichuris vulpis), and Giardia spp. during active infection in owned dogs visiting dog parks in Western Canada.

Methods

A total of 774 participants were recruited from Edmonton, Alberta, Canada. Canine fecal samples were collected from seven dedicated off-leash dog parks. Participating dog owners responded to a questionnaire regarding their dogs’ signalment, previous veterinary history, and use of parasite-preventive products. Fecal samples were tested using zinc sulfate centrifugation combined with coproantigen testing.

Results

The overall prevalence of canine intestinal parasites in client-owned dogs was similar to previous studies conducted in the US. Mean age of dogs tested was 4 years, with puppies and older dogs having higher rates of infection than the mean. Fecal flotation centrifugation found 3.2% hookworm, ascarid, whipworm, and Giardia spp.-positive infections. Coproantigen testing identified 5.8% positive infections, including all of the above that were detected using fecal flotation centrifugation.

Conclusions

Coproantigen testing detected more hookworm, ascarid, whipworm, and Giardia spp.-positive samples in addition to detecting all positive results found using fecal flotation centrifugation. Fecal flotation centrifugation combined with coproantigen testing improves sensitivity over flotation alone and may detect pre-patent or sub-clinical infections in dogs visiting public dog parks.

Graphical Abstract
Effects of different training intensities in high-intensity interval training (HIIT) on maximal aerobic velocity, hematological and muscle-damage markers in healthy young adults
Authors: Rhibi Fatma , Abderrahman Abderraouf Ben , Prioux Jacques , Clark Cain C. T. , Bideau Benoît , Besbes Sophia , Hackney Anthony C. , Granacher Urs , Zouhal Hassane
Published: August 2022

This study aimed to examine the effects of two high-intensity interval training programs (HIIT) on maximal aerobic velocity (MAV), hematological variations and muscle damage markers in young healthy adults. Twenty-nine male physical education students, aged 20.3 ± 3.3 years, volunteered to participate in this study, and were randomly assigned to a control group (CG, n = 9) or two intervention groups (group 1 or 2). Intervention group 1 (n = 10) exercised at 100% of their MAV (EG100) while group 2 (n = 10) exercised at 110% MAV (EG110). Before and after the eight week training program, blood samples were drawn at rest, before, and after an intermittent exercise. Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), C reactive protein (CRP), creatine kinase (CK) concentrations and hematological parameters (white blood cells [WBC], monocytes [MO], lymphocytes [LY], neutrophil [NE]) and lactate dehydrogenase (LDH) were measured. Post-hoc tests showed that MAV was significantly higher in EG110 compared to EG100 after HIIT (p < 0.01, ηp2 = 0.05), whilst ALAT, ASAT, and CPR were significantly lower (p < 0.01; 0.02 < ηp2 < 0.11) in EG110 compared to EG100. Moreover, post-hoc tests indicated that LY decreased significantly (p < 0.001, ηp2 = 0.21) only for EG110. Furthermore, there were significant positive correlations for both EG100 and EG110 between MAV and ALAT (r = 0.66, p = 0.044 and r = 0.64, p = 0.041 respectively), CK (r = 0.67, p = 0.031 and r = 0.86, p = 0.030, respectively), LDH (r = 0.74, p = 0.014, and r = 0.071, p = 0.021, respectively). In addition, there was a significant positive correlation for both, EG100 and EG110 between MAV and LY (r = 0.79, p < 0.01; r = 0.72, p < 0.05, respectively). Concerning the relationship between MAV and NE, there was a significant positive correlation (r = 0.66; p < 0.05) only for EG110. Findings from this study revealed that HIIT at 110% MAV was more efficient to improve MAV and reduce muscle damage. In addition, we observed significant associations between performance improvements (MAV) and markers of muscle damage.
Rabbit targeted genomic sequences after heterologous hybridization using human exome
Authors: Iannuccelli Nathalie , Sarry Julien , Billon Yvon , Aymard Patrick , Helies Virginie , Cabau Cédric , Donnadieu Cécile , Demars Julie
Published: August 2022

Objective

Causal mutations for major genes that underlie a broad range of morphological traits are often located within exons of genes that then affect protein functions. Non-model organism genetic studies are not easy to perform due to the lack of genome-wide molecular tools such as SNP genotyping array. Genotyping-By-Sequencing (GBS) methods offer an alternative. Consequently, we used this approach that is focused on the exome to target and identify major genes in rabbit populations.

Data description

We used a heterologous enrichment method before sequencing, allowing us to capture the rabbit exome using the marketed human panel since mammal protein coding genes are well conserved across the phylogenic tree of species. This targeted strategy was performed on 52 French rabbits from 5 different French strains (Californian, New-Zealand, Castor, Chinchilla and Laghmere). We generated 3.4 billion sequencing reads and approximately 29–140 million of reads per DNA sample. The expected exome coverage per sample ranged between 118 and 566X.

The present dataset could be useful for the scientific community working on rabbit species in order to (i) improve the annotation of the rabbit reference genome Oryctolagus cuniculus (OryCun2.0), (ii) enrich the characterization of polymorphisms segregating in rabbits and (iii) evaluate the genetic biodiversity in different rabbit strains.

Raw sequences were deposited in the European Nucleotide Archive (ENA) at the European Molecular Biology Laboratory- European Bioinformatics Institute (EMBL-EBI) data portal under bioproject accession number PRJEB37917.
Long-term cost-effectiveness of quality of diabetes care; experiences from private and public diabetes centers in Iran
Authors: Shahtaheri Rahill Sadat , Bayazidi Yahya , Davari Majid , Kebriaeezadeh Abbas , Yousefi Sepideh , Hezaveh Alireza Mahdavi , Sadeghi Abolfazl , aL Lami Ahmed Hayder Mohsin , Abbasian Hadi
Published: August 2022

Background

The quality of health care has a significant impact on both patients and the health system in terms of long-term costs and health consequences. This study focuses on determining the long-term cost-effectiveness in quality of diabetes care in two different settings (private/public) using longitudinal patient-level data in Iran.

Methods

By extracting patients intermediate biomedical markers in under-treatment type 2 diabetes patients(T2DP) in a longitudinal retrospective study and by applying the localized UKPDS diabetes model, lifetime health outcomes including life expectancy, quality-adjusted Life expectancy (QALE) and direct medical costs of managing disease and related complications from a healthcare system perspective was predicted. Costs and utility decrements had derived on under-treatment T2DP from 7 private and 8 Public diabetes centers. We applied two steps sampling mehods to recruit the needed sample size (cluster and random sampling). To cope with first and second-order uncertainty, we used Monte-Carlo simulation and bootstrapping techniques. Both cost and utility variables were discounted by 3% in the base model.

Results

In a 20-year time horizon, according to over 5 years of quality of care data, outcomes-driven in the private sector will be more effective and more costly (5.17 vs. 4.95 QALE and 15,385 vs. 8092). The incremental cost-effectiveness ratio (ICER) was $33,148.02 per QALE gained, which was higher than the national threshold.

Conclusion

Although quality of care in private diabetes centers resulted in a slight increase in the life expectancy in T2DM patients, it is associated with unfavorable costs, too. Private-sector in management of T2DM patients, compared with public (governmental) diabetic Centers, is unlikely to be cost-effective in Iran.