bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of assist-as-needed robotic gait training on the gait pattern post stroke: a randomized controlled trial
Authors: Alingh J. F. , Fleerkotte B. M. , Groen B. E. , Rietman J. S. , Weerdesteyn V. , van Asseldonk E. H. F. , Geurts A. C. H. , Buurke J. H. 
Published: February 2021

AbstractBackgroundRegaining gait capacity is an important rehabilitation goal post stroke. Compared to clinically available robotic gait trainers, robots with an assist-as-needed approach and multiple degrees of freedom (AANmDOF) are expected to support motor learning, and might improve the post-stroke gait pattern. However, their benefits compared to conventional gait training have not yet been shown in a randomized controlled trial (RCT). The aim of this two-center, assessor-blinded, RCT was to compare the effect of AANmDOFrobotic to conventional training on the gait pattern and functional gait tasks during post-stroke inpatient rehabilitation.MethodsThirty-four participants with unilateral, supratentorial stroke were enrolled (< 10 weeks post onset, Functional Ambulation Categories 3–5) and randomly assigned to six weeks of AANmDOFrobotic (combination of training in LOPES-II and conventional gait training) or conventional gait training (30 min, 3–5 times a week), focused on pre-defined training goals. Randomization and allocation to training group were carried out by an independent researcher. External mechanical work (WEXT), spatiotemporal gait parameters, gait kinematics related to pre-defined training goals, and functional gait tasks were assessed before training (T0), after training (T1), and at 4-months follow-up (T2).ResultsTwo participants, one in each group, were excluded from analysis because of discontinued participation after T0, leaving 32 participants (AANmDOFrobotic n = 17; conventional n = 15) for intention-to-treat analysis. In both groups, WEXThad decreased at T1 and had become similar to baseline at T2, while gait speed had increased at both assessments. In both groups, most spatiotemporal gait parameters and functional gait tasks had improved at T1 and T2. Except for step width (T0–T1) and paretic step length (T0–T2), there were no significant group differences at T1 or T2 compared to T0. In participants with a pre-defined goal aimed at foot clearance, paretic knee flexion improved more in the AANmDOFrobotic group compared to the conventional group (T0–T2).ConclusionsGenerally, AANmDOFrobotic training was not superior to conventional training for improving gait pattern in subacute stroke survivors. Both groups improved their mechanical gait efficiency. Yet, AANmDOFrobotic training might be more effective to improve specific post-stroke gait abnormalities such as reduced knee flexion during swing.Trial registrationRegistry number Netherlands Trial Register (www.trialregister.nl): NTR5060. Registered 13 February 2015.
Managing head and neck cancer patients during the COVID-19 pandemic: the experience of a tertiary referral center in southern Italy
Authors: Longo Francesco , Trecca Eleonora M. C. , D’Ecclesia Aurelio , Copelli Chiara , Tewfik Karim , Manfuso Alfonso , Pederneschi Nicola , Mastromatteo Annalisa , Russo Matteo Aldo , Pansini Antonio , Lacerenza Luca M. , Marano Pier Gerardo , Cassano Lazzaro 
Published: February 2021

Abstract
Background
The medical community has been deeply involved in fighting the Coronavirus disease 2019 (COVID-19) pandemic and, as a consequence, the care of non-COVID-19 patients has been impacted. However, the treatment of head and neck cancer patients is not deferrable, and an integrated strategy is required. The aim of the current article is to present the experience in the management of head and neck patients during the COVID-19 pandemic at the research hospital “Casa Sollievo della Sofferenza”. This review contains replicable and widely usable instructions on how to avoid delays in the diagnosis and treatment of head and neck tumors and to ensure a gradual return to elective procedures.

Main text
The Head and Neck Department of the research hospital “Casa Sollievo della Sofferenza” includes an Otolaryngology and a Maxillofacial Surgery Unit, both of which deal with the diagnosis and treatment of benign and malignant pathologies of the head and neck, as well as urgent/emergent consultations and surgical procedures that necessitate time sensitive operative management, such as cochlear implantation (CI). Given these premises and the complexity of the Department, the “COVID-19 organizing protocol” of the research hospital “Casa Sollievo della Sofferenza” was divided into two phases in accordance with the different stages of the pandemic and the priority of treatment. Special attention was given to the medical surveillance of health care workers and hospitalized patients, to the organization of the outpatient clinic and the operating setting as well as to the implementation of telehealth systems.

Conclusions
The COVID-19 pandemic is going to be a long-term situation with lasting effects on the public health and the entire society. Therefore, an efficient health care system has to adopt a double strategy: always being ready for a “new wave” of the pandemic and not forgetting non-COVID-19 patients, among whom head and neck cancer patients represent a priority. More than 1 year since the first outbreak in Wuhan, this review offers a unique and helpful perspective that incorporates awareness of the disease.
USP16 regulates castration-resistant prostate cancer cell proliferation by deubiquitinating and stablizing c-Myc
Authors: Ge Jianchao , Yu Wandong , Li Junhong , Ma Hangbin , Wang Pengyu , Zhou Yinghao , Wang Yang , Zhang Jun , Shi Guowei 
Published: February 2021

Abstract
Background
c-Myc, a well-established oncogene, plays an important role in the initiation and progression of various cancers, including prostate cancer. However, its mechanism in cancer cell remains largely unknown and whether there exist a deubiquitinase targeting c-Myc also remains elusive.

Methods
Bioinformatic analysis and shRNA screening methods were used to identify potential deubiquitinases that correlate with c-Myc gene signature. Cell proliferation and viability were measured by Cell-Counting-Kit 8 and colony formation assays. A mouse xenograft model of PC3 cells was established to confirm the function of USP16 in vivo. The interaction between USP16 and c-Myc protein was assessed by co-immunoprecipitation and protein co-localization assays. Immunohistochemistry staining was performed to detect the expression of USP16, Ki67, and c-Myc in xenograft tissues and clinical tumour tissues. Furthermore, the correlation between USP16 and c-Myc was confirmed by RNA sequencing.

Results
Functional analyses identified USP16, known as a deubiquitinase, was strongly correlated with the c-Myc gene signature. Depletion of USP16 was shown to significantly suppress the growth of PCa cells both in vitro and in vivo. Co-immunoprecipitation and ubiquitination assays confirmed that USP16 served as a novel deubiquitinase of c-Myc and overexpression of c-Myc significantly rescued the effects of USP16 disruption. Immunohistochemistry staining and RNA-seq tactics were further used to confirm the positive correlation between USP16 and c-Myc expression. Expression of USP16 in human PCa tissues was higher than that seen in normal prostate tissues and its high expression was found associated with poor prognosis.

Conclusions
USP16 serves as a novel deubiquitinase of c-Myc. Downregulation of USP16 markedly suppressed PCa cell growth both in vitro and in vivo. USP16 regulates PCa cell proliferation by deubiquitinating and stabilizing c-Myc, making it a potential therapeutic candidate for the treatment of PCa.
Efficacy and safety of biosimilar CT-P17 versus reference adalimumab in subjects with rheumatoid arthritis: 24-week results from a randomized study
Authors: Kay Jonathan , Jaworski Janusz , Wojciechowski Rafal , Wiland Piotr , Dudek Anna , Krogulec Marek , Jeka Slawomir , Zielinska Agnieszka , Trefler Jakub , Bartnicka-Maslowska Katarzyna , Krajewska-Wlodarczyk Magdalena , Klimiuk Piotr A. , Lee Sang Joon , Bae Yun Ju , Yang Go Eun , Yoo Jae Kyoung , Furst Daniel E. , Keystone Edward 
Published: February 2021

Abstract
Background
To demonstrate equivalent efficacy of the proposed high-concentration (100 mg/ml), citrate-free adalimumab biosimilar CT-P17 to European Union-approved adalimumab (EU-adalimumab) in subjects with active rheumatoid arthritis (RA).

Methods
This randomized, double-blind phase III study (ClinicalTrials.gov, NCT03789292) randomized (1:1) subjects with active RA at 52 centers to receive CT-P17 or EU-adalimumab 40 mg subcutaneously every 2 weeks until week 52. Results to week 24 are reported here. The primary endpoint was 20% improvement by American College of Rheumatology criteria (ACR20) response rate at week 24. Equivalence was concluded if the corresponding confidence intervals (CIs) for the estimate of treatment difference were within predefined equivalence margins: − 15 to 15% (95% CI; European Medicines Agency assumption); − 12 to 15% (90% CI; Food and Drug Administration assumption). Additional efficacy, pharmacokinetic, usability, safety, and immunogenicity endpoints were evaluated.

Results
648 subjects were randomized (324 CT-P17; 324 EU-adalimumab). The ACR20 response rate at week 24 was 82.7% (n = 268/324) in both groups (intention-to-treat population). The 95% CI (− 5.94 to 5.94) and 90% CI (− 4.98 to 4.98) were within predefined equivalence margins for both assumptions and equivalent efficacy was concluded. Additional endpoints and overall safety were comparable between groups. Mean trough serum concentrations of CT-P17 were slightly higher than those of EU-adalimumab. Immunogenicity was slightly lower numerically for the CT-P17 group than for the EU-adalimumab group.

Conclusions
CT-P17 and EU-adalimumab have equivalent efficacy and comparable safety and immunogenicity in subjects with active RA. Overall safety of CT-P17 is consistent with the known safety profile of reference adalimumab.

Trial registration
ClinicalTrials.gov, NCT03789292. Registered 28 December 2018—retrospectively registered.
NAMPT/SIRT2-mediated inhibition of the p53-p21 signaling pathway is indispensable for maintenance and hematopoietic differentiation of human iPS cells
Authors: Xu Yun , Nasri Masoud , Dannenmann Benjamin , Mir Perihan , Zahabi Azadeh , Welte Karl , Morishima Tatsuya , Skokowa Julia 
Published: February 2021

Abstract
Background
Nicotinamide phosphoribosyltransferase (NAMPT) regulates cellular functions through the protein deacetylation activity of nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins (SIRTs). SIRTs regulate functions of histones and none-histone proteins. The role of NAMPT/SIRT pathway in the regulation of maintenance and differentiation of human-induced pluripotent stem (iPS) cells is not fully elucidated.

Methods
We evaluated the effects of specific inhibitors of NAMPT or SIRT2 on the pluripotency, proliferation, survival, and hematopoietic differentiation of human iPS cells. We also studied the molecular mechanism downstream of NAMPT/SIRTs in iPS cells.

Results
We demonstrated that NAMPT is indispensable for the maintenance, survival, and hematopoietic differentiation of iPS cells. We found that inhibition of NAMPT or SIRT2 in iPS cells induces p53 protein by promoting its lysine acetylation. This leads to activation of the p53 target, p21, with subsequent cell cycle arrest and induction of apoptosis in iPS cells. NAMPT and SIRT2 inhibition also affect hematopoietic differentiation of iPS cells in an embryoid body (EB)-based cell culture system.

Conclusions
Our data demonstrate the essential role of the NAMPT/SIRT2/p53/p21 signaling axis in the maintenance and hematopoietic differentiation of iPS cells.
Sympathetic stimulation increases serum lactate concentrations in patients admitted with sepsis: implications for resuscitation strategies
Authors: Jagan Nikhil , Morrow Lee E. , Walters Ryan W. , Plambeck Robert W. , Patel Tej M. , Moore Douglas R. , Malesker Mark A. 
Published: February 2021

Abstract
Background
Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis.

Methods
Retrospective analysis of prospectively collected clinical data from four community-based hospitals and one academic medical center. 8173 adults were included. Heart rate (HR) was used as a surrogate marker of sympathetic stimulation. HR, MAP, and lactate levels were measured upon presentation.

Results
MAP and HR interacted to affect lactate levels with the highest levels observed in patients with low MAP and high HR (3.6 mmol/L) and the lowest in patients with high MAP and low HR (2.2 mmol/L). The overall mortality rate was 12.4%. Each 10 beats/min increase in HR increased the odds of death 6.0% (95% CI 2.6% to 9.4%), each 1 mmol/L increase in lactate increased the odds of death 20.8% (95% CI 17.4% to 24.2%), whereas each 10 mmHg increase in MAP reduced the odds of death 12.3% (95% CI 9.2% to 15.4%). However, HR did not moderate or mediate the association between lactate and death.

Conclusions
In septic patients, lactate production was associated with increased sympathetic activity (HR ≥ 90) and hypotension (MAP < 65 mmHg) and was a significant predictor of mortality. Because HR, lactate, and MAP were associated with mortality, our data support the present strategy of using these measurements to gauge severity of illness upon presentation. Since HR did not moderate or mediate the association between lactate and death, criticisms alleging that lactate caused by sympathetic stimulation is adaptive (i.e., less harmful) do not appear substantiated.
Multi-omics analysis of aniline-degrading bacterium, Delftia sp. K82
Authors: Lee Sang-Yeop , Yun Sung Ho , Lee Hayoung , Seo Giwan , Kim Seung Il 
Published: February 2021

AbstractDelftia sp. K82 is a soil bacterium capable of utilizing monocyclic aromatic hydrocarbons, including aniline, as its sole carbon and nitrogen source. In this study, the genome analysis of Delftia sp. K82 was completed and the genome data (6117 protein-coding genes and 62 RNA genes) were utilized for proteomic and transcriptomic analysis of Delftia sp. K82 cultured in aniline culture medium. Using these multi-omics approaches (genomics, transcriptomics, and proteomics), complete gene clusters for aniline biodegradation pathways were identified and transcriptomic or proteomic sets specifically induced in aniline culture conditions were elucidated. These data provide multi-layered information on the metabolic characteristics of Delftia sp. K82. The findings suggest that multi-omics approaches are useful analytical tools for the elucidation of the metabolic diversity of soil bacteria and for the identification of novel metabolic enzymes.
Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy
Authors: Troncoso Mayarling Francisca , Pavez Mario , Wilson Carlos , Lagos Daniel , Duran Javier , Ramos Sebastián , Barrientos Genaro , Silva Patricio , Llanos Paola , Basualto-Alarcón Carla , Westenbrink B. Daan , Lavandero Sergio , Estrada Manuel 
Published: February 2021

Abstract
Background
Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake—via AMP-activated protein kinase (AMPK)—after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR).

Methods
Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of β-myosin heavy chain (β-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR).

Results
Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated β-mhc, Hk2 and Pfk2 mRNA levels.

Conclusion
These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.
Successful treatment of post chemotherapy esophageal cicatricial atresia in a pediatric patient with anaplastic large cell lymphoma through minimally invasive esophagectomy: a case report
Authors: Hozaka Yuto , Sasaki Ken , Nishikawa Takuro , Onishi Shun , Noda Masahiro , Tsuruda Yusuke , Uchikado Yasuto , Kita Yoshiaki , Arigami Takaaki , Mori Shinichiro , Maemura Kosei , Ieiri Satoshi , Kawano Yoshifumi , Natsugoe Shoji , Ohtsuka Takao 
Published: February 2021

Abstract
Background
Anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell lymphoma, which is a rare type of non-Hodgkin lymphoma. ALCL rarely presents in the gastrointestinal tract, and the esophageal involvement in of ALCL is extremely rare.

Case presentation
An 11-year-old boy who complained of abdominal pain and cough was diagnosed with ALK-positive ALCL on the basis of systemic lymphadenopathy findings and immunohistochemistry results of pleural effusion. Although remission was observed after chemotherapy at 5 months after diagnosis, dysphagia persisted, and esophagoscopy revealed a severe stricture in the middle thoracic esophagus. At 9 months after diagnosis, allogeneic bone marrow transplantation was performed to ensure that complete remission was maintained; however, dysphagia and saliva retention did not improve. Approximately 10 months after diagnosis, esophagoscopy revealed a blind end in the middle thoracic esophagus, similar to that in congenital esophageal atresia. Subsequently, we performed minimally invasive subtotal esophagectomy under thoracoscopy and laparoscopy and gastric conduit reconstruction via the retrosternal route more than 2 years after allogeneic bone marrow transplantation. The final pathological diagnosis was esophageal atresia with esophagitis, with no malignancy. During postoperative evaluation, the patient required swallowing training for a few months, although no major complications were noted. Oral intake was possible, and complete remission was maintained at 14 month post-surgery.

Conclusions
Oncologists must consider the possibility of acquired esophageal cicatricial atresia as a complication during chemotherapy for ALCL. If esophageal obstruction or esophageal atresia occur and if remission is maintained, esophagectomy and esophageal reconstruction are useful treatment options for maintaining oral intake.
Feasibility of the Go2Play Active Play intervention for increasing physical and social development in children with intellectual disabilities
Authors: McGarty Arlene , Jones Nathalie , Rutherford Katie , Westrop Sophie , Sutherland Lara , Jahoda Andrew , Melville Craig 
Published: February 2021

Abstract
Introduction
An active play is designed to increase children’s physical activity levels and fundamental movement skills through outdoor play and is well-suited to the needs of children with intellectual disabilities. However, no active play interventions have included children with intellectual disabilities. This study aims to investigate the feasibility of a school-based active play intervention for children with intellectual disabilities.

Method
Children aged 7–12 years who had intellectual disabilities and were independently ambulatory were eligible. This single-group 17-week intervention was implemented in two additional support needs schools. It consisted of a weekly 1-h active play session incorporating 30 min of structured games and 30 min of free play. Feasibility of recruitment/retention, adherence, and outcome measures were investigated. Outcome measures included school-based physical activity (ActiGraph GT3X+ accelerometer), fundamental movement skills (Test of Gross Motor Development-2), and social interactions (Playground Observation of Peer Engagement). Staff feedback was collected via open-ended questionnaire. Feasibility was investigated using descriptive statistics and questionnaire data analyzed using thematic analysis. Potential pre-post changes were investigated for school-based physical activity, fundamental movement skills, and social interactions using paired samples t tests. The progression criteria were (1) > 50% of eligible participants recruited, (2) > 50% of recruited participants retained, (3) > 50% of active play sessions spent in MVPA, and (4) > 50% of participants complete outcome measurements.

Results
All progression criteria were met. Recruitment and retention rates were 100% (n=21 participants). Intervention adherence was high, based on data from n=1 school, with 90% of participants attending all sessions. Measuring physical activity using accelerometry and fundamental movement skills using the Test of Gross Motor Development-2 were feasible. The Playground Observation of Peer Engagement tool to measure social interactions was not feasible. The only significant increase post-intervention was for social interactions during structured play (pre–post mean difference: –1.46, 95% CI −1.99, −0.93). Staff feedback was positive with the intervention well received by schools and potential benefits post-intervention identified by teachers.

Conclusion
The Go2Play Active Play intervention is feasible for children with intellectual disabilities. Future research should further investigate feasibility and implementation on a larger scale using a pilot cluster randomised controlled trial.

Trial registration
ISRCTN registry: ISRCTN10277566.
How the wisdom of crowds, and of the crowd within, are affected by expertise
Authors: Fiechter Joshua L. , Kornell Nate 
Published: February 2021

AbstractWe investigated the effect of expertise on the wisdom of crowds. Participants completed 60 trials of a numerical estimation task, during which they saw 50–100 asterisks and were asked to estimate how many stars they had just seen. Experiment 1 established that both inner- and outer-crowd wisdom extended to our novel task: Single responses alone were less accurate than responses aggregated across a single participant (showing inner-crowd wisdom) and responses aggregated across different participants were even more accurate (showing outer-crowd wisdom). In Experiment 2, prior to beginning the critical trials, participants did 12 practice trials with feedback, which greatly increased their accuracy. There was a benefit of outer-crowd wisdom relative to a single estimate. There was no inner-crowd wisdom effect, however; with high accuracy came highly restricted variance, and aggregating insufficiently varying responses is not beneficial. Our data suggest that experts give almost the same answer every time they are asked and so they should consult the outer crowd rather than solicit multiple estimates from themselves.