bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commercial head-mounted display virtual reality for upper extremity rehabilitation in chronic stroke: a single-case design study
Authors: Erhardsson Mattias , Alt Murphy Margit , Sunnerhagen Katharina S. 
Published: November 2020

AbstractBackgroundRehabilitation is crucial for maximizing recovery after stroke. Rehabilitation activities that are fun and rewarding by themselves can be more effective than those who are not. Gamification with virtual reality (VR) exploits this principle. This single-case design study probes the potential for using commercial off-the-shelf, room-scale head-mounted virtual reality for upper extremity rehabilitation in individuals with chronic stroke, the insights of which can inform further research.MethodsA heterogeneous volunteer sample of seven participants living with stroke were recruited through advertisement. A single-case design was employed with a 5-week baseline (A), followed by a 10-week intervention (B) and a 6-month follow-up. Upper extremity motor function was assessed with validated kinematic analysis of drinking task. Activity capacity was assessed with Action Research Arm Test, Box and Block Test and ABILHAND questionnaire. Assessments were done weekly and at follow-up. Playing games on a VR-system with head-mounted display (HTC Vive) was used as rehabilitation intervention. Approximately 300 games were screened and 6 tested. Visual analysis and Tau-U statistics were used to interpret the results.ResultsVisual analysis of trend, level shift and overlap as well as Tau-U statistics indicated improvement of Action Research Arm Test in six participants. Four of these had at least a moderate Tau-U score (0.50–0.92), in at least half of the assessed outcomes. These four participants trained a total of 361 to 935 min. Two out of four participants who were able to perform the drinking task, had the highest training dose (> 900 min) and showed also improvements in kinematics. The predominant game played was Beat Saber. No serious adverse effects related to the study were observed, one participant interrupted the intervention phase due to a fall at home.ConclusionsThis first study of combining commercial games, a commercial head-mounted VR, and commercial haptic hand controls, showed promising results for upper extremity rehabilitation in individuals with chronic stroke. By being affordable yet having high production values, as well as being an easily accessible off-the-shelf product, this variant of VR technology might facilitate widespread adaption. Insights garnered in this study can facilitate the execution of future studies.Trial registrationThe study was registered at researchweb.org (project number 262331, registered 2019-01-30,https://www.researchweb.org/is/vgr/project/262331) prior to participant enrolment.
The clinical and translational research activities at the INT – IRCCS “Fondazione Pascale” cancer center (Naples, Italy) during the COVID-19 pandemic
Authors:   and the INT-Pascale COVID-19 Crisis Unit, Buonaguro Franco M. , Botti Gerardo , Ascierto Paolo Antonio , Pignata Sandro , Ionna Franco , Delrio Paolo , Petrillo Antonella , Cavalcanti Ernesta , Di Bonito Maurizio , Perdonà Sisto , De Laurentiis Michelino , Fiore Francesco , Palaia Raffaele , Izzo Francesco , D’Auria Stefania , Rossi Virginia , Menegozzo Simona , Piccirillo Mauro , Celentano Egidio , Cuomo Arturo , Normanno Nicola , Tornesello Maria Lina , Saviano Rocco , Barberio Daniela , Buonaguro Luigi , Giannoni Giovanni , Muto Paolo , Miscio Leonardo , Bianchi Attilio A. M. 
Published: November 2020

AbstractCOVID-19 pandemic following the outbreak in China and Western Europe, where it finally lost the momentum, is now devastating North and South America. It has not been identified the reason and the molecular mechanisms of the two different patterns of the pulmonary host responses to the virus from a minimal disease in young subjects to a severe distress syndrome (ARDS) in older subjects, particularly those with previous chronic diseases (including diabetes) and cancer. The Management of the Istituto Nazionale Tumori - IRCCS “Fondazione Pascale” in Naples (INT-Pascale), along with all Health professionals decided not to interrupt the treatment of those hospitalized and to continue, even if after a careful triage in order not to allow SARS-CoV-2 positive subjects to access, to take care of cancer patients with serious conditions. Although very few (n = 3) patients developed a symptomatic COVID-19 and required the transfer to a COVID-19 area of the Institute, no patients died during the hospitalization and completed their oncology treatment. Besides monitoring of the patients, all employees of the Institute (physicians, nurses, researchers, lawyers, accountants, gatekeepers, guardians, janitors) have been tested for a possible exposure. Personnel identified as positive, has been promptly subjected to home quarantine and subdued to health surveillance. One severe case of respiratory distress has been reported in a positive employees and one death of a family member. Further steps to home monitoring of COVID-19 clinical course have been taken with the development of remote Wi-Fi connected digital devices for the detection of early signs of respiratory distress, including heart rate and oxygen saturation.In conclusion cancer care has been performed and continued safely also during COVID-19 pandemic and further remote home strategies are in progress to ensure the appropriate monitoring of cancer patients.
Nicotinamide, a vitamin B3 ameliorates depressive behaviors independent of SIRT1 activity in mice
Authors: Liu Zhuxi , Li Caiqin , Fan Xuelian , Kuang Yifang , Zhang Xu , Chen Lei , Song Jinjing , Zhou Ying , Takahashi Eiki , He Guang , Li Weidong 
Published: November 2020

AbstractSirtuin 1 (SIRT1), is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase and a candidate gene for depression. Nicotinamide (NAM), a form of vitamin B3, is reported as a potential inhibitor of SIRT1. Our previous study found that the 24-h-restraint stress could induce long-term depressive-like phenotypes in mice. These mice displayed increased SIRT1 activity. Here, we studied whether NAM was capable of attenuating depressive behaviors through inhibiting SIRT1 activity. Surprisingly, the application of NAM significantly reversed the depressive behaviors but increased SIRT1 activity further. In contrast, the level of adenosine triphosphate (ATP) was reduced in the restraint model for depression, and recovered by the administration of NAM. Furthermore, theSirt1flox/flox; Nestin-Cremice exhibited antidepressant behaviors and increased ATP levels. These data suggest that ATP plays an important role in depression pathogenesis, and NAM could be a potential treatment method for depression by regulating ATP independent of SIRT1 activity.
Clinical implication of cellular vaccine in glioma: current advances and future prospects
Authors: Yan Yuanliang , Zeng Shuangshuang , Gong Zhicheng , Xu Zhijie 
Published: November 2020

AbstractGliomas, especially glioblastomas, represent one of the most aggressive and difficult-to-treat human brain tumors. In the last few decades, clinical immunotherapy has been developed and has provided exceptional achievements in checkpoint inhibitors and vaccines for cancer treatment. Immunization with cellular vaccines has the advantage of containing specific antigens and acceptable safety to potentially improve cancer therapy. Based on T cells, dendritic cells (DC), tumor cells and natural killer cells, the safety and feasibility of cellular vaccines have been validated in clinical trials for glioma treatment. For TAA engineered T cells, therapy mainly uses chimeric antigen receptors (IL13Rα2, EGFRvIII and HER2) and DNA methylation-induced technology (CT antigen) to activate the immune response. Autologous dendritic cells/tumor antigen vaccine (ADCTA) pulsed with tumor lysate and peptides elicit antigen-specific and cytotoxic T cell responses in patients with malignant gliomas, while its pro-survival effect is biased. Vaccinations using autologous tumor cells modified with TAAs or fusion with fibroblast cells are characterized by both effective humoral and cell-mediated immunity. Even though few therapeutic effects have been observed, most of this therapy showed safety and feasibility, asking for larger cohort studies and better guidelines to optimize cellular vaccine efficiency in anti-glioma therapy.
Dexosomes as a cell-free vaccine for cancer immunotherapy
Authors: Nikfarjam Sepideh , Rezaie Jafar , Kashanchi Fatah , Jafari Reza 
Published: November 2020

AbstractDendritic cells (DCs) secrete vast quantities of exosomes termed as dexosomes. Dexosomes are symmetric nanoscale heat-stable vesicles that consist of a lipid bilayer displaying a characteristic series of lipid and protein molecules. They include tetraspanins and all established proteins for presenting antigenic material such as the major histocompatibility complex class I/II (MHC I/II) and CD1a, b, c, d proteins and CD86 costimulatory molecule. Dexosomes contribute to antigen-specific cellular immune responses by incorporating the MHC proteins with antigen molecules and transferring the antigen-MHC complexes and other associated molecules to naïve DCs. A variety of ex vivo and in vivo studies demonstrated that antigen-loaded dexosomes were able to initiate potent antitumor immunity. Human dexosomes can be easily prepared using monocyte-derived DCs isolated by leukapheresis of peripheral blood and treated ex vivo by cytokines and other factors. The feasibility of implementing dexosomes as therapeutic antitumor vaccines has been verified in two phase I and one phase II clinical trials in malignant melanoma and non small cell lung carcinoma patients. These studies proved the safety of dexosome administration and showed that dexosome vaccines have the capacity to trigger both the adaptive (T lymphocytes) and the innate (natural killer cells) immune cell recalls. In the current review, we will focus on the perspective of utilizing dexosome vaccines in the context of cancer immunotherapy.
Impact of a computerized decision support tool deployed in two intensive care units on acute kidney injury progression and guideline compliance: a prospective observational study
Authors: Bourdeaux Christopher , Ghosh Erina , Atallah Louis , Palanisamy Krishnamoorthy , Patel Payaal , Thomas Matthew , Gould Timothy , Warburton John , Rivers Jon , Hadfield John 
Published: November 2020

Abstract
Background
Acute kidney injury (AKI) affects a large proportion of the critically ill and is associated with worse patient outcomes. Early identification of AKI can lead to earlier initiation of supportive therapy and better management. In this study, we evaluate the impact of computerized AKI decision support tool integrated with the critical care clinical information system (CCIS) on patient outcomes. Specifically, we hypothesize that integration of AKI guidelines into CCIS will decrease the proportion of patients with Stage 1 AKI deteriorating into higher stages of AKI.

Methods
The study was conducted in two intensive care units (ICUs) at University Hospitals Bristol, UK, in a before (control) and after (intervention) format. The intervention consisted of the AKIN guidelines and AKI care bundle which included guidance for medication usage, AKI advisory and dashboard with AKI score. Clinical data and patient outcomes were collected from all patients admitted to the units. AKI stage was calculated using the Acute Kidney Injury Network (AKIN) guidelines. Maximum AKI stage per admission, change in AKI stage and other metrics were calculated for the cohort. Adherence to eGFR-based enoxaparin dosing guidelines was evaluated as a proxy for clinician awareness of AKI.

Results
Each phase of the study lasted a year, and a total of 5044 admissions were included for analysis with equal numbers of patients for the control and intervention stages. The proportion of patients worsening from Stage 1 AKI decreased from 42% (control) to 33.5% (intervention), p = 0.002. The proportion of incorrect enoxaparin doses decreased from 1.72% (control) to 0.6% (intervention), p < 0.001. The prevalence of any AKI decreased from 43.1% (control) to 37.5% (intervention), p < 0.05.

Conclusions
This observational study demonstrated a significant reduction in AKI progression from Stage 1 and a reduction in overall development of AKI. In addition, a reduction in incorrect enoxaparin dosing was also observed, indicating increased clinical awareness. This study demonstrates that AKI guidelines coupled with a newly designed AKI care bundle integrated into CCIS can impact patient outcomes positively.
Low temperature tolerance of three Aedes albopictus strains (Diptera: Culicidae) under constant and fluctuating temperature scenarios
Authors: Tippelt Lisa , Werner Doreen , Kampen Helge 
Published: November 2020

AbstractBackgroundAedes albopictus, a vector of numerous viruses and filarial worms, has already established in 20 countries in Europe, mainly colonising subtropical regions. Continuing adaptation to climatic conditions in temperate areas would probably result in a spread to more northern European countries, producing an increasing risk of mosquito-borne pathogen transmission over a much greater area. Based on previous studies showing thatAe. albopictusis able to overwinter in Germany, this study aims to determine more exactly its ecological limits of enduring low temperatures.MethodsNon-diapausing and experimentally induced diapausing eggs of three differentAe. albopictusstrains (tropical, subtropical and temperate origins) were exposed to four different regimes with constant temperatures and three different regimes with fluctuating temperatures in a course of a day for a minimum of 2 and a maximum of 30 days. The hatching rate of larvae after cold exposure of the eggs was taken as a measure of cold tolerance.ResultsThe experiments showed that the tropicalAe. albopictusstrain had a lower cold tolerance than the subtropical and the temperate strains. The eggs of all used strains were able to survive constant temperatures as low as −5 °C for an exposure period of 30 days, while constant temperatures as low as −10 °C were endured for 2 days by the tropical strain and for 10 and 20 days by the subtropical and temperate strains, respectively. At fluctuating temperatures, both the subtropical and the temperate strains exhibited hatching under all temperature regimes, even with a minimum temperature of −10 °C, whereas the tropical strain ceased hatching after an exposure period of 30 days under the temperature regime with a minimum temperature of −10 °C. The analyses showed that the temperature played the major role in interpreting the hatching rates of the eggs. The condition, whether the eggs were diapausing or not, had no significant influence, although results indicated a slightly higher cold tolerance of diapausing eggs at −10 °C.ConclusionsIt must be expected that subtropical and temperate strains ofAe. albopictusare able to withstand common central European winters and are able to establish in considerable parts of the continent.
Histone modifications associated with gene expression and genome accessibility are dynamically enriched at Plasmodium falciparum regulatory sequences
Authors: Tang Jingyi , Chisholm Scott A. , Yeoh Lee M. , Gilson Paul R. , Papenfuss Anthony T. , Day Karen P. , Petter Michaela , Duffy Michael F. 
Published: November 2020

Abstract
Background
The malaria parasite Plasmodium falciparum has an unusually euchromatic genome with poorly conserved positioning of nucleosomes in intergenic sequences and poorly understood mechanisms of gene regulation. Variant histones and histone modifications determine nucleosome stability and recruit trans factors, but their combinatorial contribution to gene regulation is unclear.

Results
Here, we show that the histone H3 acetylations H3K18ac and H3K27ac and the variant histone Pf H2A.Z are enriched together at regulatory sites upstream of genes. H3K18ac and H3K27ac together dynamically mark regulatory regions of genes expressed during the asexual life cycle. In contrast, H3K4me1 is depleted in intergenic sequence and dynamically depleted upstream of expressed genes. The temporal pattern of H3K27ac and H3K18ac enrichment indicates that they accumulate during S phase and mitosis and are retained at regulatory sequences until at least G1 phase and after cessation of expression of the cognate genes. We integrated our ChIPseq data with existing datasets to show that in schizont stages H3K18ac, H3K27ac and Pf H2A.Z colocalise with the transcription factor PfAP2-I and the bromodomain protein PfBDP1 and are enriched at stably positioned nucleosomes within regions of exposed DNA at active transcriptional start sites. Using transient transfections we showed that sequences enriched with colocalised H3K18ac, H3K27ac and Pf H2A.Z possess promoter activity in schizont stages, but no enhancer-like activity.

Conclusions
The dynamic H3 acetylations define P. falciparum regulatory sequences and contribute to gene activation. These findings expand the knowledge of the chromatin landscape that regulates gene expression in P. falciparum.
Characterization of the dual functional effects of heat shock proteins (HSPs) in cancer hallmarks to aid development of HSP inhibitors
Authors: Zhang Zhao , Jing Ji , Ye Youqiong , Chen Zhiao , Jing Ying , Li Shengli , Hong Wei , Ruan Hang , Liu Yaoming , Hu Qingsong , Wang Jun , Li Wenbo , Lin Chunru , Diao Lixia , Zhou Yubin , Han Leng 
Published: November 2020

Abstract
Background
Heat shock proteins (HSPs), a representative family of chaperone genes, play crucial roles in malignant progression and are pursued as attractive anti-cancer therapeutic targets. Despite tremendous efforts to develop anti-cancer drugs based on HSPs, no HSP inhibitors have thus far reached the milestone of FDA approval. There remains an unmet need to further understand the functional roles of HSPs in cancer.

Methods
We constructed the network for HSPs across ~ 10,000 tumor samples from The Cancer Genome Atlas (TCGA) and ~ 10,000 normal samples from Genotype-Tissue Expression (GTEx), and compared the network disruption between tumor and normal samples. We then examined the associations between HSPs and cancer hallmarks and validated these associations from multiple independent high-throughput functional screens, including Project Achilles and DRIVE. Finally, we experimentally characterized the dual function effects of HSPs in tumor proliferation and metastasis.

Results
We comprehensively analyzed the HSP expression landscape across multiple human cancers and revealed a global disruption of the co-expression network for HSPs. Through analyzing HSP expression alteration and its association with tumor proliferation and metastasis, we revealed dual functional effects of HSPs, in that they can simultaneously influence proliferation and metastasis in opposite directions. We experimentally characterized the dual function of two genes, DNAJC9 and HSPA14, in lung cancer cells. We further demonstrated the generalization of this dual direction of associations between HSPs and cancer hallmarks, suggesting the necessity to more carefully evaluate HSPs as therapeutic targets and develop highly specific HSP inhibitors for cancer intervention.

Conclusions
Our study furnishes a holistic view of functional associations of HSPs with cancer hallmarks to aid the development of HSP inhibitors as well as other drugs in cancer therapy.
Genotype imputation and variability in polygenic risk score estimation
Authors: Chen Shang-Fu , Dias Raquel , Evans Doug , Salfati Elias L. , Liu Shuchen , Wineinger Nathan E. , Torkamani Ali 
Published: November 2020

Abstract
Background
Polygenic risk scores (PRSs) are a summarization of an individual’s genetic risk for a disease or trait. These scores are being generated in research and commercial settings to study how they may be used to guide healthcare decisions. PRSs should be updated as genetic knowledgebases improve; however, no guidelines exist for their generation or updating.

Methods
Here, we characterize the variability introduced in PRS calculation by a common computational process used in their generation—genotype imputation. We evaluated PRS variability when performing genotype imputation using 3 different pre-phasing tools (Beagle, Eagle, SHAPEIT) and 2 different imputation tools (Beagle, Minimac4), relative to a WGS-based gold standard. Fourteen different PRSs spanning different disease architectures and PRS generation approaches were evaluated.

Results
We find that genotype imputation can introduce variability in calculated PRSs at the individual level without any change to the underlying genetic model. The degree of variability introduced by genotype imputation differs across algorithms, where pre-phasing algorithms with stochastic elements introduce the greatest degree of score variability. In most cases, PRS variability due to imputation is minor (< 5 percentile rank change) and does not influence the interpretation of the score. PRS percentile fluctuations are also reduced in the more informative tails of the PRS distribution. However, in rare instances, PRS instability at the individual level can result in singular PRS calculations that differ substantially from a whole genome sequence-based gold standard score.

Conclusions
Our study highlights some challenges in applying population genetics tools to individual-level genetic analysis including return of results. Rare individual-level variability events are masked by a high degree of overall score reproducibility at the population level. In order to avoid PRS result fluctuations during updates, we suggest that deterministic imputation processes or the average of multiple iterations of stochastic imputation processes be used to generate and deliver PRS results.
Effects of balance training on balance performance in youth: role of training difficulty
Authors: Schedler Simon , Tenelsen Florian , Wich Laura , Muehlbauer Thomas 
Published: November 2020

Abstract
Background
Cross-sectional studies have shown that balance performance can be challenged by the level of task difficulty (e.g., varying stance conditions, sensory manipulations). However, it remains unclear whether the application of different levels of task difficulty during balance training (BT) leads to altered adaptations in balance performance. Thus, we examined the effects of BT conducted under a high versus a low level of task difficulty on balance performance.

Methods
Forty male adolescents were randomly assigned to a BT program using a low (BT-low: n = 20; age: 12.4 ± 2.0 yrs) or a high (BT-high: n = 20; age: 12.5 ± 2.5 yrs) level of balance task difficulty. Both groups trained for 7 weeks (2 sessions/week, 30–35 min each). Pre- and post-training assessments included measures of static (one-legged stance [OLS] time), dynamic (10-m gait velocity), and proactive (Y-Balance Test [YBT] reach distance, Functional Reach Test [FRT]; Timed-Up-and-Go Test [TUG]) balance.

Results
Significant main effects of Test (i.e., pre- to post-test improvements) were observed for all but one balance measure (i.e., 10-m gait velocity). Additionally, a Test x Group interaction was detected for the FRT in favor of the BT-high group (Δ + 8%, p < 0.001, d = 0.35). Further, tendencies toward significant Test x Group interactions were found for the YBT anterior reach (in favor of BT-high: Δ + 9%, p < 0.001, d = 0.60) and for the OLS with eyes opened and on firm surface (in favor of BT-low: Δ + 31%, p = 0.003, d = 0.67).

Conclusions
Following 7 weeks of BT, enhancements in measures of static, dynamic, and proactive balance were observed in the BT-high and BT-low groups. However, BT-high appears to be more effective for increasing measures of proactive balance, whereas BT-low seems to be more effective for improving proxies of static balance.

Trial registration
Current Controlled Trials ISRCTN83638708 (Retrospectively registered 19th June, 2020).