bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actuation Spaces Synthesis of Lower-Mobility Parallel Mechanisms Based on Screw Theory
Authors: Li Shihua , Shan Yanxia , Yu Jingjun , Ke Yaxiong 
Published: February 2021

AbstractThe lower-mobility parallel mechanism has been widely used in the engineering field due to its numerous excellent characteristics. However, little work has been devoted to the actuator selection and placement that best satisfy the system’s functional requirements during concept design. In this study, a unified approach for synthesizing the actuation spaces of both rigid and flexure parallel mechanisms has been presented, and all possible combinations of inputs could be obtained, laying a theoretical foundation for the subsequent optimization of inputs. According to the linear independence of actuation space and constraint space of the lower-mobility parallel mechanism, a general expression of actuation spaces in the format of screw systems is deduced, a unified synthesis process for the lower-mobility parallel mechanism is derived, and the efficiency of the method is validated with two selective examples based on screw theory. This study presents a theoretical framework for the input selection problems of parallel mechanisms, aiming to help designers select and place actuators in a correct and even optimal way after the configuration design.
Comparative efficacy, safety and durability of dolutegravir relative to common core agents in treatment-naïve patients infected with HIV-1: an update on a systematic review and network meta-analysis
Authors: Nickel Katharina , Halfpenny Nicholas J. A. , Snedecor Sonya J. , Punekar Yogesh Suresh 
Published: February 2021

Abstract
Background
The objective of this study was to assess the durability of response of dolutegravir (DTG) as an antiretroviral core agent by comparing its efficacy and safety with other recommended or commonly used core agents up to 96-weeks (W96).

Methods
A previously published systematic review was updated to identify phase 3/4 randomised controlled trials (RCTs) of core agents in treatment-naïve HIV-1 patients. Efficacy [virologic suppression (VS), CD4+ cell change from baseline] and safety [adverse events [AEs], discontinuations, drug-related AEs [DRAEs]] were analysed at W96 using Bayesian network meta-analysis (NMA) adjusting for nucleoside/nucleotide reverse transcriptase inhibitors' (NRTIs') backbone. Subgroups of patients with VL > 100,000 copies/mL or CD4+ ≤ 200 cells/μL at baseline were analysed separately.

Results
The NMA included 20 studies reporting data at W96. A higher proportion of patients receiving DTG achieved VS compared to those on protease inhibitors [PI:Range:8.7%(CrI:3.1,16.0)-19.9%(10.8,30.5)], efavirenz [EFV:6.9%(1.3,10.8)] and cobicistat-boosted elvitegravir [EVG/c:8.2%(0.2,17.4)], and similar but numerically higher compared to rilpivirine [RPV:5.0%(− 2.8,12.5)], raltegravir [RAL:2.9%(− 1.6,7.7)] and bictegravir [BIC:2.7%(− 2.7,10.6)]. The probability that more patients on DTG would achieve VS at W96 compared to any other core agent was greater than 80%. A higher proportion of patients on DTG achieved VS compared to PI/rs [Range:33.1%(13.6,50.4)-45.3%(24.1,61.6)] and RAL [16.7%(3.3,31.2)] in patients with VL > 100,000 copies/mL at baseline, and similar VS was achieved in patients with CD4+ ≤ 200 cells/μL at baseline. DTG also achieved greater increase in CD4+ cells from baseline compared to EFV [32.6(10.7,54.7)], ritonavir-boosted darunavir [DRV/r:25.7(3.6,48.1)] and BIC [24.7(1.5,47.7)]. Patients receiving DTG had lower odds of discontinuing therapy by W96 compared to PI/rs, EFV, RAL and EVG/c. Patients on DTG had lower odds of experiencing an adverse event (AE) compared to patients on EFV [odds ratio:0.6(0.3,0.9)], ATV/r [0.4(0.3,0.6)] and LPV/r [0.3(0.2,0.5)]. For patients on DTG, the odds of experiencing a drug-related AE were lower than the odds for patients on EFV [0.3(0.2,0.4)], comparable to patients on RAL [1.1(0.8,1.4)] and higher than those on BIC [1.5(1.1,2.0)].

Conclusion
Un-boosted integrase inhibitors had better efficacy and similar safety compared to PI/rs at W96 in treatment-naïve patients with HIV-1, with DTG being among the most efficacious core agent, particularly in patients with baseline VL > 100,000 copies/mL or ≤ 200 CD4+ cells/μL, who can be difficult to treat.
Accelerometer-measured physical activity and its impact on sleep quality in patients suffering from restless legs syndrome
Authors: Reimers A. K. , Heidenreich V. , Bittermann H-J , Knapp G. , Reimers C. D. 
Published: February 2021

Abstract
Background
The primary symptoms of restless legs syndrome (RLS) are sleep onset insomnia and difficulty to maintain sleep. Previous studies have shown that regular physical activity can reduce the risk of developing RLS. However, the relationship between physical activity and sleep quality parameters in individuals suffering from RLS has not yet been investigated by applying accelerometry. Thus, the present study investigates the impact of physical activity (measuring both intensity levels and duration of physical activity) during the day (7–12 h, 12–18 h, 18–23 h) on sleep quality in patients suffering from idiopathic RLS by applying a real-time approach.

Methods
In a sample of 47 participants suffering from idiopathic RLS, physical activity and sleep quality were measured over one week using accelerometers. For data analysis, physical activity levels and step counts during three periods of the day (morning, afternoon, evening) were correlated with sleep quality parameters of the subsequent night.

Results
This observational study revealed that in most instances physical activity was not correlated with sleep parameters (two exceptions exist: steps taken in the morning were negatively correlated with periodic leg movements during sleep, and physical activity in the evening was negatively correlated with total sleep time). The physical activity levels of the participants in this study, however, were unexpectedly high compared to population-level data and variance in physical activity was low. The average activity was 13,817 (SD = 4086) steps and 347 (SD = 117) minutes of moderate physical activity per day in females, and 10,636 (SD = 3748) steps and 269 (SD = 69) minutes of moderate physical activity in males, respectively. Participants did not engage in any vigorous physical activity.

Conclusions
Further interventional studies are needed to investigate the daily effects of different intensities of physical activity on RLS symptoms.
Group versus individual treatment for substance use disorders: a study protocol for the COMDAT trial
Authors: Karsberg Sidsel Helena , Pedersen Mads Uffe , Hesse Morten , Thylstrup Birgitte , Pedersen Michael Mulbjerg 
Published: February 2021

Abstract
Background
Alcohol and other drug use disorders contribute substantially to the global burden of illness. The majority of people with substance use disorders do not receive any treatment for their problems, and developing treatments that are attractive and effective to patients should be a priority. However, whether treatment is best delivered in a group format or an individual format has only been studied to a very limited degree. The COMDAT (Combined Drug and Alcohol Treatment) trial evaluates the feasibility, acceptability, and cost effectiveness of MOVE group (MOVE-G) treatment versus MOVE individual (MOVE-I) treatment in four community-based outpatient treatment centres in Denmark.

Methods
A two-arm non-inferiority trial comparing MOVE-I (Pedersen et al., Drug Alcohol Depend 218:108363, 2020) with MOVE-G a combined group treatment for both alcohol use disorder and drug use disorder. The primary objective is to examine whether MOVE-G is non-inferior to MOVE-I in relation to abstinence from drug and/or alcohol, number of sessions received, and completion of treatment as planned. All participants will receive treatment based on cognitive behavioral therapy and motivational interviewing, vouchers for attendance and text reminders, as well as medication as needed (MOVE). Participants (n = 300) will be recruited over a one-year period at four public treatment centers in four Danish municipalities. A short screening will determine eligibility and randomization status. Hereafter, participants will be randomized to the two treatment arms. A thorough baseline assessment will be conducted approximately 1 week after randomization. Follow-up assessments will be conducted at 9 months post-randomization. In addition, patients’ use of drugs and alcohol, and patients’ wellbeing will be measured in all sessions. The main outcome measures are drug and alcohol intake at 9 months follow-up, number of sessions attended, and dropout from treatment.

Discussion
The present study will examine the potential and efficacy of combined groups (patients with alcohol and drug disorders in the same group) versus individually based treatment both based on the treatment method MOVE (Pedersen et al., Drug Alcohol Depend 218:108363, 2020).

Trial registration
ISRCTN88025085, registration date 30/06/2020.
Cryoneurolysis for the management of chronic pain in patients with knee osteoarthritis; a double-blinded randomized controlled sham trial
Authors: Nygaard Niels-Peter Brøchner , Koch-Jensen Carsten , Vægter Henrik Bjarke , Wedderkopp Niels , Blichfeldt-Eckhardt Morten , Gram Bibi 
Published: February 2021

AbstractObjectivePain is the principal symptom in knee osteoarthritis (OA). Current non-operative treatment options have only moderate effects and often patients experience persistent pain or side-effects. Novel advances in the field of cryoneurolysis applies low temperatures to disrupt nerve signaling at the painful area, providing pain relief. The primary aim of this randomized controlled trial (RCT) is to investigate if cryoneurolysis is superior to sham at decreasing pain intensity 2 weeks after the intervention in patients with knee OA. Secondary aims are to explore effects on pain, quality of life and functional performance over 24 months.MethodsThis two-arm, parallel-group RCT, approved by the Regional Ethics Committee, will randomly allocate patients (n = 94) to a cryoneurolysis intervention group + standardized education and exercise (CRYO) or a sham group + standardized education and exercise (SHAM) (1:1 ratio). Both groups will be assessed at baseline, 2 weeks post intervention, post education and exercise and at 6, 12 and 24 months after cryoneurolysis. The primary outcome is the NRS knee pain intensity score assessed 2 weeks post the intervention. Secondary outcome measures include functional performance (chair-stand test, 40 m walk, stair test and maximum voluntary contraction of the knee), patient reported outcomes (quality of life (EQ5D), Knee and osteoarthritis outcome scores (KOOS), among others), use of analgesics, and adverse events over 24 months.Impact statementCryoneurolysis could potentially provide an effective, safe and non-pharmacological therapeutic option to treat pain in OA patients. The potential benefits include increased functional capacity and quality of life as a result of significant pain relief and improved benefits of physical exercise.Trial registrationClinicaltrials.gov,NCT03774121, registered 3 March 2018,http://www.clinicaltrials.gov
Predictive factors for intraoperative blood loss in surgery for adolescent idiopathic scoliosis
Authors: Tang Chris Yuk Kwan , Kamath Vijay H. D. , Cheung Prudence Wing Hang , Cheung Jason Pui Yin 
Published: February 2021

Abstract
Background
Adolescent idiopathic scoliosis (AIS) is a common spinal deformity. Posterior spinal fusion remains an important surgical treatment for AIS. This study aims to determine the predictive factors for intraoperative blood loss in AIS surgery.

Methods
Patients who had undergone posterior spinal fusion for adolescent idiopathic scoliosis in a single university hospital were reviewed over a 7-year period. Predictive factors for intra-operative blood loss were studied by multivariate analysis to derive a regression model. Receiver operating characteristic analysis was performed to determine the cut-off values of factors contributing to significant intraoperative blood loss (≥500 ml).

Results
Two hundred and twelve patients were included. Intraoperative blood loss was found to be correlated with gender (rs = 0.30 (0.17–0.43)), preoperative hemoglobin level (rs = 0.20 (0.04–0.31)), preoperative Cobb angle (rs = 0.20 (0.02–0.29)), number of fused levels (rs = 0.46 (0.34–0.58)), operation duration (rs = 0.65 (0.54–0.75)), number of anchors (rs = 0.47 (0.35–0.59)), and p-value ranged from < 0.001 to < 0.05. Significant intraoperative blood loss was influenced by the male gender, operation duration greater than 257.5 min and more than 10 anchors used.

Conclusions
Male gender, increased operation duration and higher number of anchors predicted higher intra-operative blood loss.
Patients and family caregivers report high treatment expectations during palliative chemotherapy: a longitudinal prospective study
Authors: Ikander Tine , Jeppesen Stefan Starup , Hansen Olfred , Raunkiær Mette , Dieperink Karin Brochstedt 
Published: February 2021

Abstract
Background
When discussing treatment options and future care, it is important to understand the expectations of patients and family caregivers related to palliative chemotherapy and to identify patterns in patients’ quality of life. The study aims were to evaluate differences in treatment expectations and quality of life between patients with thoracic cancer (non-small-cell lung cancer, small-cell lung cancer and mesothelioma) who were < 70 and ≥ 70 years of age and receiving palliative chemotherapy and to assess family caregivers’ treatment expectations.

Methods
A prospective longitudinal study included patients with thoracic cancer receiving outpatient palliative chemotherapy at a university hospital in Denmark and their family caregivers. Patients’ treatment expectations and quality of life were assessed three times during treatment with a survey of treatment expectations and the Functional Assessment of Cancer Therapy – General questionnaire. Family caregivers’ treatment expectations were assessed once.

Results
A total of 48 patients and 36 family caregivers participated between 2018 and 2019. No statistically significant age-related differences in treatment expectations and quality of life were identified. 28% of patients aged < 70 years and 7% of those aged ≥70 years expected a cure. Among family caregivers, 36% expected a cure. Across both age groups, mean total quality of life scores significantly decreased from 73.2 at first palliative chemotherapy cycle to 70.5 at third cycle (p = 0.02). No meaningful changes were found in quality of life within either age group. A subgroup analysis found no significant between-group differences in quality of life. Mean physical well-being score for all patients decreased from 20.3 at first cycle to 18.4 at third cycle (p = 0.03) and mean emotional well-being score decreased from 15.4 at first cycle to 14.6 at third cycle (p = 0.04).

Conclusion
This study emphasizes the importance of initiating conversations about treatment expectations and paying attention to expectations that may differ by the age of the patient and between patients and family caregivers. Addressing treatment expectations among patients and family caregivers and monitoring quality of life among patients is important in clinical practice.
mTOR-dependent dysregulation of autophagy contributes to the retinal ganglion cell loss in streptozotocin-induced diabetic retinopathy
Authors: Madrakhimov Sanjar Batirovich , Yang Jin Young , Kim Jin Ha , Han Jung Woo , Park Tae Kwann 
Published: February 2021

Abstract
Background
Neurodegeneration, an early event in the pathogenesis of diabetic retinopathy (DR), precedes clinically detectable microvascular damage. Autophagy dysregulation is considered a potential cause of neuronal cell loss, however underlying mechanisms remain unclear. The mechanistic target of rapamycin (mTOR) integrates diverse environmental signals to coordinate biological processes, including autophagy. Here, we investigated the role of mTOR signaling in neuronal cell death in DR.

Methods
Diabetes was induced by a single intraperitoneal injection of streptozotocin and tissue samples were harvested at 1, 2, 3, 4, and 6 months of diabetes. Early-stage of DR was investigated in 1-month-diabetic mice treated with phlorizin (two daily subcutaneous injections at a dose of 200 mg/kg of body weight during the last 7 full days of the experiment and the morning of the 8th day, 3 h before sacrifice) or rapamycin (daily intraperitoneal injections, at a dose of 3 mg/kg for the same period as for phlorizin treatment). The effect of autophagy modulation on retinal ganglion cells was investigated in 3-months-diabetic mice treated with phlorizin (two daily subcutaneous injections during the last 10 full days of the experiment and the morning of the 11th day, 3 h before sacrifice) or MHY1485 (daily i.p. injections, at a dose of 10 mg/kg for the same period as for phlorizin treatment). Tissue samples obtained from treated/untreated diabetic mice and age-matched controls were used for Western blot and histologic analysis.

Results
mTOR-related proteins and glucose transporter 1 (GLUT1) was upregulated at 1 month and downregulated in the following period up to 6 months. Diabetes-induced neurodegeneration was characterized by an increase of apoptotic marker—cleaved caspase 3, a decrease of the total number of cells, and NeuN immunoreactivity in the ganglion cell layer, as well as an increase of autophagic protein. Insulin-independent glycemic control restored the mTOR pathway activity and GLUT1 expression, along with a decrease of autophagic and apoptotic proteins in 3-months-diabetic mice neuroretina. However, blockade of autophagy using MHY1485 resulted in a more protective effect on ganglion cells compared with phlorizin treatment.

Conclusion
Collectively, our study describes the mechanisms of neurodegeneration through the hyperglycemia/ mTOR/ autophagy/ apoptosis pathway.
Neuroendocrine patterns underlying seasonal song and year-round territoriality in male black redstarts
Authors: Villavicencio Camila P. , Windley Harriet , D’Amelio Pietro B. , Gahr Manfred , Goymann Wolfgang , Quispe René 
Published: February 2021

Abstract
Background
The connection between testosterone and territoriality in free-living songbirds has been well studied in a reproductive context, but less so outside the breeding season. To assess the effects of seasonal androgenic action on territorial behavior, we analyzed vocal and non-vocal territorial behavior in response to simulated territorial intrusions (STIs) during three life-cycle stages in free-living male black redstarts: breeding, molt and nonbreeding. Concurrently, we measured changes in circulating testosterone levels, as well as the mRNA expression of androgen and estrogen receptors and aromatase in the preoptic, hypothalamic and song control brain areas that are associated with social and vocal behaviors.

Results
Territorial behavior and estrogen receptor expression in hypothalamic areas did not differ between stages. But plasma testosterone was higher during breeding than during the other stages, similar to androgen receptor and aromatase expression in the preoptic area. The expression of androgen receptors in the song control nucleus HVC was lower during molt when birds do not sing or sing rarely, but similar between the breeding and the nonbreeding stage. Nevertheless, some song spectral features and the song repertoire differed between breeding and nonbreeding. Territorial behavior and song rate correlated with the expression of steroid receptors in hypothalamic areas, and in the song control nucleus lMAN.

Conclusions
Our results demonstrate seasonal modulation of song, circulating testosterone levels, and brain sensitivity to androgens, but a year-round persistency of territorial behavior and estrogen receptor expression in all life-cycle stages. This suggests that seasonal variations in circulating testosterone concentrations and brain sensitivity to androgens is widely uncoupled from territorial behavior and song activity but might still affect song pattern. Our study contributes to the understanding of the complex comparative neuroendocrinology of song birds in the wild.
The Kickstart Walk Assist System for improving balance and walking function in stroke survivors: a feasibility study
Authors: Yao Jiajia , Sado Takashi , Wang Wenli , Gao Jiawen , Zhao Yichao , Qi Qi , Mukherjee Mukul 
Published: February 2021

Abstract
Background
Compared with traditional physical therapy for stroke patients, lower extremity exoskeletons can provide patients with greater endurance and more repeatable and controllable training, which can reduce the therapeutic burden of the therapist. However, most exoskeletons are expensive, heavy or require active power to be operated. Therefore, a lighter, easy to wear, easy to operate, low-cost technology for stroke rehabilitation would be a welcome opportunity for stroke survivors, caregivers and clinicians. One such device is the Kickstart Walk Assist system and the purpose of this study was to determine feasibility of using this unpowered exoskeleton device in a sample of stroke survivors.

Methods
Thirty stroke survivors were enrolled in the study and experienced walking with the Kickstart exoskeleton device that provided spring-loaded assistance during gait. After 5 days of wearing the exoskeleton, participants were evaluated in the two states of wearing and not wearing the exoskeleton. Outcome measures included: (a) spatio-temporal gait measures, (b) balance measures and (c) exoskeleton-use feedback questionnaire.

Results
In comparison to not wearing the device, when participants wore the Kickstart walking system, weight bearing asymmetry was reduced. The time spent on the 10-m walk test was also reduced, but there was no difference in the timed-up-and-go test (TUGT). Gait analysis data showed reduction in step time and double support time. Stroke survivors were positive about the Kickstart walking system’s ability to improve their balance, speed and gait. In addition, their confidence level and willingness to use the device was also positive.

Conclusions
These findings show the feasibility of using the Kickstart walking system for improving walking performance in stroke survivors. Our future goal is to perform a longer duration study with more comprehensive pre- and post-testing in a larger sample of stroke survivors.
Trial registration Chinese Clinical Trial Registry, ChiCTR2000032665. Registered 5 May 2020—Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=53288