bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of low-intensity repetitive transcranial magneTic brAin stimUlation foR people living with mUltiple Sclerosis (TAURUS): study protocol for a randomised controlled trial
Authors: Makowiecki Kalina , Stevens Natasha , Cullen Carlie L. , Zarghami Amin , Nguyen Phuong Tram , Johnson Lewis , Rodger Jennifer , Hinder Mark R. , Barnett Michael , Young Kaylene M. , Taylor Bruce V. 
Published: August 2022

Abstract
Background
Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease, characterised by oligodendrocyte death and demyelination. Oligodendrocyte progenitor cells can differentiate into new replacement oligodendrocytes; however, remyelination is insufficient to protect neurons from degeneration in people with MS. We previously reported that 4 weeks of daily low-intensity repetitive transcranial magnetic stimulation (rTMS) in an intermittent theta-burst stimulation (iTBS) pattern increased the number of new myelinating oligodendrocytes in healthy adult mice. This study translates this rTMS protocol and aims to determine its safety and tolerability for people living with MS. We will also perform magnetic resonance imaging (MRI) and symptom assessments as preliminary indicators of myelin addition following rTMS.

Methods
Participants (N = 30, aged 18–65 years) will have a diagnosis of relapsing-remitting or secondary progressive MS. ≤2 weeks before the intervention, eligible, consenting participants will complete a physical exam, baseline brain MRI scan and participant-reported MS symptom assessments [questionnaires: Fatigue Severity Scale, Quality of Life (AQoL-8D), Hospital Anxiety and Depression Scale; and smartphone-based measures of cognition (electronic symbol digit modalities test), manual dexterity (pinching test, draw a shape test) and gait (U-Turn test)]. Participants will be pseudo-randomly allocated to rTMS (n=20) or sham (placebo; n=10), stratified by sex. rTMS or sham will be delivered 5 days per week for 4 consecutive weeks (20 sessions, 6 min per day). rTMS will be applied using a 90-mm circular coil at low-intensity (25% maximum stimulator output) in an iTBS pattern. For sham, the coil will be oriented 90° to the scalp, preventing the magnetic field from stimulating the brain. Adverse events will be recorded daily. We will evaluate participant blinding after the first, 10th and final session. After the final session, participants will repeat symptom assessments and brain MRI, for comparison with baseline. Participant-reported assessments will be repeated at 4-month post-allocation follow-up.

Discussion
This study will determine whether this rTMS protocol is safe and tolerable for people with MS. MRI and participant-reported symptom assessments will serve as preliminary indications of rTMS efficacy for myelin addition to inform further studies.

Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12619001196134. Registered on 27 August 2019
Assessing the associations between Aedes larval indices and dengue risk in Kalutara district, Sri Lanka: a hierarchical time series analysis from 2010 to 2019
Authors: Liyanage Prasad , Tozan Yesim , Tissera Hasitha Aravinda , Overgaard Hans J. , Rocklöv Joacim 
Published: August 2022

Abstract
Background
Dengue is a major public health problem in Sri Lanka. Aedes vector surveillance and monitoring of larval indices are routine, long-established public health practices in the country. However, the association between Aedes larval indices and dengue incidence is poorly understood. It is crucial to evaluate lagged effects and threshold values of Aedes larval indices to set pragmatic targets for sustainable vector control interventions.

Methods
Monthly Aedes larval indices and dengue cases in all 10 Medical Officer of Health (MOH) divisions in Kalutara district were obtained from 2010 to 2019. Using a novel statistical approach, a distributed lag non-linear model and a two-staged hierarchical meta-analysis, we estimated the overall non-linear and delayed effects of the Premise Index (PI), Breteau Index (BI) and Container Index (CI) on dengue incidence in Kalutara district. A set of MOH division-specific variables were evaluated within the same meta-analytical framework to determine their moderator effects on dengue risk. Using generalized additive models, we assessed the utility of Aedes larval indices in predicting dengue incidence.

Results
We found that all three larval indices were associated with dengue risk at a lag of 1 to 2 months. The relationship between PI and dengue was homogeneous across MOH divisions, whereas that with BI and CI was heterogeneous. The threshold values of BI, PI and CI associated with dengue risk were 2, 15 and 45, respectively. All three indices showed a low to moderate accuracy in predicting dengue risk in Kalutara district.

Conclusions
This study showed the potential of vector surveillance information in Kalutara district in developing a threshold-based, location-specific early warning system with a lead time of 2 months. The estimated thresholds are nonetheless time-bound and may not be universally applicable. Whenever longitudinal vector surveillance data areavailable, the methodological framework we propose here can be used to estimate location-specific Aedes larval index thresholds in any other dengue-endemic setting.

Graphical Abstract
Whole genome sequencing reveals the independent clonal origin of multifocal ileal neuroendocrine tumors
Authors: Mäkinen Netta , Zhou Meng , Zhang Zhouwei , Kasai Yosuke , Perez Elizabeth , Kim Grace E. , Thirlwell Chrissie , Nakakura Eric , Meyerson Matthew 
Published: August 2022

AbstractBackgroundSmall intestinal neuroendocrine tumors (SI-NETs) are the most common neoplasms of the small bowel. The majority of tumors are located in the distal ileum with a high incidence of multiple synchronous primary tumors. Even though up to 50% of SI-NET patients are diagnosed with multifocal disease, the mechanisms underlying multiple synchronous lesions remain elusive.MethodsWe performed whole genome sequencing of 75 de-identified synchronous primary tumors, 15 metastases, and corresponding normal samples from 13 patients with multifocal ileal NETs to identify recurrent somatic genomic alterations, frequently affected signaling pathways, and shared mutation signatures among multifocal SI-NETs. Additionally, we carried out chromosome mapping of the most recurrent copy-number alterations identified to determine which parental allele had been affected in each tumor and assessed the clonal relationships of the tumors within each patient.ResultsAbsence of shared somatic variation between the synchronous primary tumors within each patient was observed, indicating that these tumors develop independently. Although recurrent copy-number alterations were identified, additional chromosome mapping revealed that tumors from the same patient can gain or lose different parental alleles. In addition to the previously reportedCDKN1Bloss-of-function mutations, we observed potential loss-of-function gene alterations inTNRC6B, a candidate tumor suppressor gene in a small subset of ileal NETs. Furthermore, we show that multiple metastases in the same patient can originate from either one or several primary tumors.ConclusionsOur study demonstrates major genomic diversity among multifocal ileal NETs, highlighting the need to identify and remove all primary tumors, which have the potential to metastasize, and the need for optimized targeted treatments.
Targeting clock-controlled gene Nrf2 ameliorates inflammation-induced intervertebral disc degeneration
Authors: Peng Pandi , Wang Dong , Xu Xiaolong , Wang Di , Gao Bo , Wang Han , Jia Haoruo , Shang Qiliang , Zheng Chao , Gao Chu , Mao Jianxin , Luo Zhuojing , Yang Liu , Hu Xueyu 
Published: August 2022

Abstract
Background
Intervertebral disc (IVD) is a highly rhythmic tissue, which experiences a diurnal cycle of high/low mechanical loading via the changes of activity/rest phase. There are signs that disruption of the peripheral IVD clock is related to the process of intervertebral disc degeneration (IDD). However, it is still unclear whether inflammation could disturb the IVD clock and thus induce the process of IDD.

Methods and results
In this study, we used IL-1β, a commonly used inflammatory factor, to induce IDD and found that the IVD clock was dampened in degenerated human nucleus pulposus specimens, rat nucleus pulposus (NP) tissues, and cells. In this study, we found that the circadian clock of NP cells was totally disrupted by knockdown of the core clock gene brain and muscle arnt-like protein-1 (Bmal1), which thus induced the dysfunction of NP cells. Next, we explored the mechanism of dampened clock-induced IDD and found that knockdown of Bmal1 decreased the expression of nuclear factor erythroid2-related factor 2 (NRF2), a downstream target gene of Bmal1, and increased inflammatory response, oxidative stress reaction, and apoptosis of NP cells. In addition, NRF2 activation attenuated the dysfunction of NP cells induced by the dampened IVD clock and the degenerative process of NP tissues in an organotypic tissue-explant model.

Conclusions
Taken together, our study extends the relationship between peripheral clock and IVD homeostasis and provides a potential therapeutic method for the prevention and recovery of IDD by targeting the clock-controlled gene Nrf2.
Alternatives to common approaches for training change of direction performance: a scoping review
Authors: Buhmann Robert , Stuelcken Max , Sayers Mark 
Published: August 2022

Abstract
Background
Research focuses heavily upon the effect of strength and power training on change of direction performance. The objective of this scoping review is to highlight alternative approaches to training change of direction.

Methods
Four databases (Scopus, PubMed, Web of Science and SPORTDiscus) were searched with no date restrictions. To be included studies must (i) investigate change of direction performance following an intervention or investigate the relationships between variables of interest and change of direction performance; (ii) recruit participants > 18 years old; (iii) recruit participants involved in competitive sport. The majority of included studies investigated the effect of strength and/or power training, or, relationships between strength and/or power variables with change of direction performance.

Results
Despite fewer studies, alternative training methods resulted in greater improvements (compared with strength and/or power) in change of direction performance, with smaller training durations. Few studies included reactive agility as an outcome measure.

Conclusion
Despite much of the literature focusing on strength and/or power, there are alternative training modalities that demonstrate merit for improving change of direction performance. Future studies should investigate the effect of alternative training interventions on reactive agility performance, to provide a more valid indication of transfer to competition.
Overexpressing HPGDS in adipose-derived mesenchymal stem cells reduces inflammatory state and improves wound healing in type 2 diabetic mice
Authors: Ouyang Long , Qiu Daojing , Fu Xin , Wu Aiping , Yang Pengyuan , Yang Zhigang , Wang Qian , Yan Li , Xiao Ran 
Published: August 2022

Abstract
Background
In diabetes, delayed wound healing was considered as the result of excessive recruitment and retention of pro-inflammatory cells and factors. Hematopoietic prostaglandin D synthase (HPGDS) was identified from differently expressed genes of diabetic human foot skin. HPGDS is responsible for the production of prostaglandin D2 (PGD2), an inflammatory mediator. Therefore, we aim to explore whether HPGDS could be a therapeutic target in the diabetic wound (DW).

Method
In this study, we compared gene expression profilings of diabetic human foot skin and non-diabetic human foot skin from the Gene Expression Omnibus database. We detected the characteristics of immune components in diabetic mice wound and investigated the role and underlying mechanism of the differently expressed Hpgds for the diabetic wound healing. For in vivo studies, we engineered ADSC to overexpress Hpgds (ADSCHpgds) and evaluated its effects on diabetic wound healing using a full-thickness skin wound model. For in vitro studies, we evaluated the role of ADSCHpgds conditioned medium and PGD2 on Lipopolysaccharide (LPS) induced macrophage.

Results
Hpgds was significantly down-regulated in type 2 diabetic mice wound and its deficiency delayed normal wound healing. ADSCHpgds accelerated DW healing by reducing neutrophil and CD8T cell recruitment, promoting M2 macrophage polarization and increasing the production of growth factors. ADSCHpgds conditioned medium showed superior capability in promoting M2 macrophage transition than conditioned medium derived from ADSC alone.

Conclusion
Our results demonstrated that Hpgds is required for wound healing, and ADSCHpgds could accelerate DW healing by improving anti-inflammatory state and normalizing the proliferation phase of wound healing in mice. These findings provide a new insight in the therapeutic strategy of diabetic wound.
Mesenchymal stem cell-derived extracellular vesicles protect retina in a mouse model of retinitis pigmentosa by anti-inflammation through miR-146a-Nr4a3 axis
Authors: Zhang Jia , Li Pengdong , Zhao Guifang , He Siqi , Xu Di , Jiang Weijie , Peng Qian , Li Zhaohui , Xie Zhongjian , Zhang Han , Xu Ying , Qi Ling 
Published: August 2022

Abstract
Background
Retinitis pigmentosa is a rod-cone degenerative disease that induces irreversible vision loss. This study probed the protective capacity of mesenchymal stem cell-derived small EVs (MSC-EVs) on the retinas of rd10 mice and the underlying mechanism.

Methods
MSC-EVs were injected into the vitreous of rd10 mice at postnatal day 14 and P21; morphology and function were examined at P28. The mechanism of action was explored by using co-culture of photoreceptor cell line 661 W and microglia cell line BV2.

Results
Treatment with MSC-EVs increased the survival of photoreceptors and preserved their structure. Visual function, as reflected by optomotor and electroretinogram responses, was significantly enhanced in MSC-EVs-treated rd10 mice. Mechanistically, staining for Iba1, GFAP, F4/80, CD68 and CD206 showed that MSC-EVs suppressed the activation of microglial, Müller glial and macrophages. Furthermore, western blotting showed that the treatment inhibited the NF-κB pathway. RNA-seq and qPCR showed that MSC-EVs upregulated anti-inflammatory cytokines while downregulating pro-inflammatory cytokines. MSC-EVs application in vitro decreased the number of TUNEL-positive 661 W cells co-cultured with LPS-stimulated BV2, with similar impact on the cytokine expression as in vivo study. Genetic screening predicted miR-146a to be the downstream target of MSC-EVs, which was detected in MSC-EVs and upregulated in co-cultured 661 W cells and BV2 cells after MSC-EVs treatment. Upregulation of miR-146a by using its mimic decreased the expression of the transcription factor Nr4a3, and its downregulation inhibition promoted Nr4a3 expression in both 661 W and BV2 cells. Nr4a3 was further identified as the target gene of miR-146a by dual-luciferase assay. Furthermore, overexpressing miR-146a significantly decreased the expression of LPS-induced pro-inflammatory cytokines in BV2 cells.

Conclusions
MSC-EVs delays retinal degeneration in rd10 mice mainly by its anti-inflammatory effect via the miR-146a-Nr4a3axis. Hence, MSC-EVs may be used in the treatment of neurodegenerative diseases.
JSON-based control model for SQL and NoSQL data conversion in hybrid cloud database
Authors: Zhang Lei , Pang Ke , Xu Jiangtao , Niu Bingxin 
Published: August 2022

AbstractA data interaction transformation model, XYJSON, that is suitable for all data using current standard SQL syntax and JSON document data is proposed to solve the problem of increasing development workload and difficulty caused by using different control methods for corresponding types of databases under the cloud hybrid storage. A control program was studied to control relational and NoSQL data at the same time, by establishing a general conversion model between relational and NoSQL data and converting standard SQL statements into JSON. The performance of XYJSON was compared with that of the traditional mode. The results show that the performance difference between XYJSON and the traditional mode is small. In addition, a developer survey was conducted on XYJSON for user friendliness and compatibility. All developers rated XYJSON as excellent. The current cloud hybrid storage cannot use a unified control model to realize data control. XYJSON breaks through this bottleneck, making it easier and more efficient to control different types of databases under cloud hybrid storage.
An Improved Linear Complementarity Solver for the Dynamic Analysis of Blast Loaded Structures
Authors: Khan Azam , Tariq Moiz , Ullah Asad , Hussain Arshad 
Published: August 2022

AbstractThe linear complementarity problem (LCP) approach, expedited by using the simple rigid–plastic theory, has been utilized successfully in predicting the numerical response of the ductile steel or concrete structures subjected to short-duration, high-intensity dynamic loads. The current study attempts to improve the computational stability of this powerful technique while determining the response of skeletal structures under blast loading. The performance of the Lemke LCP solver is amplified by introducing an automatic time-stepping scheme to efficiently trace the complex dynamic response using either lumped mass or continuous mass discretization. The computational efficiency of this solver is tested against carefully chosen three numerical examples, and the acquired results are in good agreement with the derived closed-form solution and results from other sources.
Effectiveness of polarized polychromatic light therapy on myofascial trigger points in chronic non-specific low back pain: a single blinded randomized controlled trial
Authors: Shiryan Ghoufran Tukaram , Amin Fatmaa Sedik , Embaby Eman Ahmed 
Published: August 2022

Abstract
Background
Phototherapy has been used for the treatment of chronic low back pain. However, the effect of linear polarized polychromatic light (PL) has not been examined on myofascial trigger points in patients with chronic non-specific low back pain (NSLBP).

Objectives
To investigate the effectiveness of PL on pain intensity, pain sensitivity of active myofascial trigger points (MTrPs) in gluteus medius (GM) and quadratus lamborum (QL) muscles, back disability, and lumbar range of motion in chronic NSLBP.

Methods
Forty-two participants of both genders with chronic NSLBP were randomly allocated into two equal groups: group A (Linear polarized polychromatic light (PL): 21 participants received polarized light therapy in the range of red and near-infrared rays on myofascial trigger points of bilateral GM and QL muscles for 5 min/point followed by stretching and strengthening exercises for 4 weeks. Group B (Sham PL): 21 participants received the same program but with sham linear polarized polychromatic light therapy. Numeric pain rating scale, pressure algometer, and Roland-Morris Disability Questionnaire were used to measure pain intensity, pain sensitivity (as represented by pain pressure threshold (PPT) of MTrPs of the target muscles and back disability respectively. Further, lumbar flexion, extension, and bilateral rotation were examined with a tape measure, while bilateral side bending were examined with a universal goniometer.

Results
After the intervention program, significant improvements (p < 0.05) in pain intensity, PPT of MTrPs of left GM (Effect Size (ES): 1.23) and bilateral QL muscles (ES Rt QL: 0.9; Lt QL: 1.56) were found in group A in comparison with group B. Nevertheless, the two groups displayed similar improvements (p > 0.05) in lumbar range of motion and back disability.

Conclusion
Linear polarized polychromatic light therapy in the range of red and near-infrared rays improves pain intensity and pain sensitivity of myofascial trigger points in chronic NSLBP.

Trial registration
PACTR, PACTR202111577053926. Registered 22 June 2019-Prospectively registered.
The risk of tibial eminence avulsion fracture with bi-unicondylar knee arthroplasty
Authors: Stoddart Jennifer C. , Garner Amy , Tuncer Mahmut , Cobb Justin P. , van Arkel Richard J. 
Published: August 2022

Aims The aim of this study was to determine the risk of tibial eminence avulsion intraoperatively for bi-unicondylar knee arthroplasty (Bi-UKA), with consideration of the effect of implant positioning, overstuffing, and sex, compared to the risk for isolated medial unicondylar knee arthroplasty (UKA-M) and bicruciate-retaining total knee arthroplasty (BCR-TKA). Methods Two experimentally validated finite element models of tibia were implanted with UKA-M, Bi-UKA, and BCR-TKA. Intraoperative loads were applied through the condyles, anterior cruciate ligament (ACL), medial collateral ligament (MCL), and lateral collateral ligament (LCL), and the risk of fracture (ROF) was evaluated in the spine as the ratio of the 95th percentile maximum principal elastic strains over the tensile yield strain of proximal tibial bone. Results Peak tensile strains occurred on the anterior portion of the medial sagittal cut in all simulations. Lateral translation of the medial implant in Bi-UKA had the largest increase in ROF of any of the implant positions (43%). Overstuffing the joint by 2 mm had a much larger effect, resulting in a six-fold increase in ROF. Bi-UKA had ~10% increased ROF compared to UKA-M for both the male and female models, although the smaller, less dense female model had a 1.4 times greater ROF compared to the male model. Removal of anterior bone akin to BCR-TKA doubled ROF compared to Bi-UKA. Conclusion Tibial eminence avulsion fracture has a similar risk associated with Bi-UKA to UKA-M. The risk is higher for smaller and less dense tibiae. To minimize risk, it is most important to avoid overstuffing the joint, followed by correctly positioning the medial implant, taking care not to narrow the bone island anteriorly. Cite this article: Bone Joint Res 2022;11(8):575–584.
Engaging hard‐to‐reach men‐who‐have‐sex‐with‐men with sexual health screening: Qualitative interviews in an Australian sex‐on‐premises‐venue and sexual health service
Authors: Ooi Catriona , Lewis David A. , Newman Christy E. 
Published: August 2022

AbstractContextCompared with the general population in Australia, men‐who‐have‐sex‐with‐men (MSM) have higher rates of HIV and sexually transmissible infections (STIs). Despite widespread advice to test regularly, a minority of these men remain “hard to reach.” We undertook qualitative interviews with a group of such men in Sydney to better understand their views and experiences in relation to sexual health screening.MethodsWe conducted semi‐structured interviews with men engaging with HIV/STI screening services at a sex‐on‐premises‐venue and the local Sexual Health Service in Greater Western Sydney. We analyzed these data for content and themes.ResultsSexual behaviors and identities were diverse, often discordant and compartmentalized from everyday lives. Overall, reported HIV/STI knowledge was poor and men did not see themselves at risk of HIV/STIs regardless of sexual behavior. Men took calculated risks and balanced with pleasure and escapism. Reasons for avoidance of testing included fear, unwillingness to disclose behavior, privacy concerns, and perceived low risk. Men viewed sexual health care as distinct from general health care. Service delivery preferences varied by service venue. Participants highlighted convenience, confidentiality, and trust as critical factors for a testing service.ConclusionA variety of testing options are needed to engage hard‐to‐reach MSM. Opportunities to enhance testing may include expanding health messaging, demystifying testing, and delinking sexual identity from sexual behavior and risk, thus promoting advantages of testing and establishing testing as standard of care.