bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug Hypersensitivity Quality of Life Questionnaire: validation procedures and first results of the Portuguese version
Authors: Dias de Castro E. , Barbosa J. , Mesquita A. M. , Caires A. , Ribeiro L. , R. Cernadas J. , Baiardini I. 
Published: May 2021

AbstractBackgroundHypersensitivity reactions to drugs are unpredictable and can be very complex and severe, even life threatening. Assess its impact on patient’s health related quality of life (HRQoL) is crucial. The Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) is the only validated disease-specific HRQoL questionnaire. We aimed to translate and cross-cultural validate the DrHy-Q to the Portuguese population. It was also our purpose to determine the impact of drug hypersensitivity on patients’ HRQoL.MethodsThe translation and cross-cultural adaptation of the DrHy-Q to Portuguese was performed according to standards. Reliability of the DrHy-Q Portuguese version was assessed in terms of internal consistency and test–retest reliability. Structural validity, divergent validity (with a generic health related QoLQ-PGWBI) and discriminant validity were also evaluated. Forty patients accepted to participate in the validation phase. The Portuguese version of the DrHy-Q was applied to 260 consecutively adult patients, studied in our Department for suspected drug hypersensitivity.ResultsThe Portuguese DrHy-Q showed adequate internal consistency (Cronbach’s ɑ = 0.938), good test–retest reliability [ICC = 0.713 (95% CI 0.488–0.850] and one-dimensional structure. No significant correlation was found between the DrHy-Q and the PGWBI total scores (r = − 0.010,p = 0.957). Two hundred of patients completed the study: 78.5% female; mean age = 44 ± 15 years. Mean DrHy-Q score was 36.8 ± 12.6. Two clinical factors significantly predict DrHy-Q total score: clinical manifestations and number of suspected drugs. Patients with anaphylaxis (β = 11.005; 95% CI 5.523; 16.487), urticaria/angioedema (β = 7.770; 95% CI 2.600; 12.940) and other manifestations (β = 7.948; 95% CI 1.933; 13.962) are more likely to have higher DrHy-Q total score than patients with maculopapular exanthema. Patients with ≥ 2 suspected drugs are also more likely to have worse QoL (β = 7.927; 95% CI 3.687; 12.166).ConclusionThe Portuguese version of DrHy-Q revealed adequate validity and reliability, indicating that it is appropriate to assess the impact of drug hypersensitivity on patients’ HRQoL, providing data for a better comprehension and management of our patients. Moreover, our results highlight that the severity of the drug hypersensitivity reaction and the number of suspected drugs have impact on patient’s DrHy-QoL.
Effects of a robot‐aided somatosensory training on proprioception and motor function in stroke survivors
Authors: Yeh I-Ling , Holst-Wolf Jessica , Elangovan Naveen , Cuppone Anna Vera , Lakshminarayan Kamakshi , Cappello Leonardo , Masia Lorenzo , Konczak Jürgen 
Published: May 2021

Abstract
Background
Proprioceptive deficits after stroke are associated with poor upper limb function, slower motor recovery, and decreased self-care ability. Improving proprioception should enhance motor control in stroke survivors, but current evidence is inconclusive. Thus, this study examined whether a robot-aided somatosensory-based training requiring increasingly accurate active wrist movements improves proprioceptive acuity as well as motor performance in chronic stroke.

Methods
Twelve adults with chronic stroke completed a 2-day training (age range: 42–74 years; median time-after-stroke: 12 months; median Fugl–Meyer UE: 65). Retention was assessed at Day 5. Grasping the handle of a wrist-robotic exoskeleton, participants trained to roll a virtual ball to a target through continuous wrist adduction/abduction movements. During training vision was occluded, but participants received real-time, vibro-tactile feedback on their forearm about ball position and speed. Primary outcome was the just-noticeable-difference (JND) wrist position sense threshold as a measure of proprioceptive acuity. Secondary outcomes were spatial error in an untrained wrist tracing task and somatosensory-evoked potentials (SEP) as a neural correlate of proprioceptive function. Ten neurologically-intact adults were recruited to serve as non-stroke controls for matched age, gender and hand dominance (age range: 44 to 79 years; 6 women, 4 men).

Results
Participants significantly reduced JND thresholds at posttest and retention (Stroke group: pretest: mean: 1.77° [SD: 0.54°] to posttest mean: 1.38° [0.34°]; Control group: 1.50° [0.46°] to posttest mean: 1.45° [SD: 0.54°]; F[2,37] = 4.54, p = 0.017, ηp2 = 0.20) in both groups. A higher pretest JND threshold was associated with a higher threshold reduction at posttest and retention (r = − 0.86, − 0.90, p ≤ 0.001) among the stroke participants. Error in the untrained tracing task was reduced by 22 % at posttest, yielding an effect size of w = 0.13. Stroke participants exhibited significantly reduced P27-N30 peak-to-peak SEP amplitude at pretest (U = 11, p = 0.03) compared to the non-stroke group. SEP measures did not change systematically with training.

Conclusions
This study provides proof-of-concept that non-visual, proprioceptive training can induce fast, measurable improvements in proprioceptive function in chronic stroke survivors. There is encouraging but inconclusive evidence that such somatosensory learning transfers to untrained motor tasks.
Trial registration Clinicaltrials.gov; Registration ID: NCT02565407; Date of registration: 01/10/2015; URL: https://clinicaltrials.gov/ct2/show/NCT02565407.
Evaluation of mitochondria in mouse oocytes following cisplatin exposure
Authors: Wang Qiaochu , Hutt Karla J. 
Published: May 2021

Abstract
Background
Cisplatin is a platinum-based chemotherapeutic that damages genomic DNA leading to cell death. It also damages mitochondrial DNA and induces high levels of mitochondrial reactive oxygen species (mtROS), further sensitising cells to apoptosis. Notably, immature oocytes are particularly vulnerable to cisplatin treatment, a common side effect of which is depletion of the primordial follicle reserve, leading to infertility and early menopause. Cisplatin is known to damage the DNA of oocytes, but the possibility that cisplatin also compromises oocyte survival and quality by damaging mitochondria, has not been investigated. To begin to address this question, neonatal mice were treated with saline or cisplatin (2 mg/kg or 4 mg/kg) and the short and long-term impacts on mitochondria in oocytes were characterised.

Results
At 6 and 24 h after treatment, mitochondrial localisation, mass and ATP content in immature oocytes were similar between groups. However, TMRM staining intensity, a marker of mitochondrial membrane potential, was decreased in immature oocytes from cisplatin treated mice compared to saline treated controls, consistent with the induction of apoptosis. When mice were super ovulated 5 weeks after exposure, the number of mature oocytes harvested from cisplatin treated mice was significantly lower than controls. Mitochondrial localisation, mass, membrane potential and ATP levels showed no differences between groups.

Conclusions
These findings suggest that mitochondrial dysfunction may contribute to the depletion of the ovarian reserve caused by cisplatin, but long-term impacts on mitochondria may be minimal as those immature oocytes that survive cisplatin treatment develop into mature oocytes with normal mitochondrial parameters.
Accessing routinely collected health data to improve clinical trials: recent experience of access
Authors: Macnair Archie , Love Sharon B. , Murray Macey L. , Gilbert Duncan C. , Parmar Mahesh K. B. , Denwood Tom , Carpenter James , Sydes Matthew R. , Langley Ruth E. , Cafferty Fay H. 
Published: May 2021

Abstract
Background
Routinely collected electronic health records (EHRs) have the potential to enhance randomised controlled trials (RCTs) by facilitating recruitment and follow-up. Despite this, current EHR use is minimal in UK RCTs, in part due to ongoing concerns about the utility (reliability, completeness, accuracy) and accessibility of the data. The aim of this manuscript is to document the process, timelines and challenges of the application process to help improve the service both for the applicants and data holders.

Methods
This is a qualitative paper providing a descriptive narrative from one UK clinical trials unit (MRC CTU at UCL) on the experience of two trial teams’ application process to access data from three large English national datasets: National Cancer Registration and Analysis Service (NCRAS), National Institute for Cardiovascular Outcomes Research (NICOR) and NHS Digital to establish themes for discussion. The underpinning reason for applying for the data was to compare EHRs with data collected through case report forms in two RCTs, Add-Aspirin (ISRCTN 74358648) and PATCH (ISRCTN 70406718).

Results
The Add-Aspirin trial, which had a pre-planned embedded sub-study to assess EHR, received data from NCRAS 13 months after the first application. In the PATCH trial, the decision to request data was made whilst the trial was recruiting. The study received data after 8 months from NICOR and 15 months for NHS Digital following final application submission. This concluded in May 2020. Prior to application submission, significant time and effort was needed particularly in relation to the PATCH trial where negotiations over consent and data linkage took many years.

Conclusions
Our experience demonstrates that data access can be a prolonged and complex process. This is compounded if multiple data sources are required for the same project. This needs to be factored in when planning to use EHR within RCTs and is best considered prior to conception of the trial. Data holders and researchers are endeavouring to simplify and streamline the application process so that the potential of EHR can be realised for clinical trials.
Identification and characterization of proteins of unknown function (PUFs) in Clostridium thermocellum DSM 1313 strains as potential genetic engineering targets
Authors: Poudel Suresh , Cope Alexander L. , O’Dell Kaela B. , Guss Adam M. , Seo Hyeongmin , Trinh Cong T. , Hettich Robert L. 
Published: May 2021

Abstract
Background
Mass spectrometry-based proteomics can identify and quantify thousands of proteins from individual microbial species, but a significant percentage of these proteins are unannotated and hence classified as proteins of unknown function (PUFs). Due to the difficulty in extracting meaningful metabolic information, PUFs are often overlooked or discarded during data analysis, even though they might be critically important in functional activities, in particular for metabolic engineering research.

Results
We optimized and employed a pipeline integrating various “guilt-by-association” (GBA) metrics, including differential expression and co-expression analyses of high-throughput mass spectrometry proteome data and phylogenetic coevolution analysis, and sequence homology-based approaches to determine putative functions for PUFs in Clostridium thermocellum. Our various analyses provided putative functional information for over 95% of the PUFs detected by mass spectrometry in a wild-type and/or an engineered strain of C. thermocellum. In particular, we validated a predicted acyltransferase PUF (WP_003519433.1) with functional activity towards 2-phenylethyl alcohol, consistent with our GBA and sequence homology-based predictions.

Conclusions
This work demonstrates the value of leveraging sequence homology-based annotations with empirical evidence based on the concept of GBA to broadly predict putative functions for PUFs, opening avenues to further interrogation via targeted experiments.
Prevalence of coccidia in domestic pigs in China between 1980 and 2019: a systematic review and meta-analysis
Authors: Gong Qing-Long , Zhao Wen-Xuan , Wang Yan-Chun , Zong Ying , Wang Qi , Yang Yang , Yang Yi , Shi Kun , Li Jian-Ming , Leng Xue , Du Rui , Zhao Quan 
Published: May 2021

Abstract
Background
Swine coccidiosis, a protozoan disease caused by coccidia, can result in diarrhoea and weight loss in piglets and even economic losses in the pig industry. Here, we report the first systematic review and meta-analysis of the prevalence of coccidia (including Eimeria spp. and Cystoisospora suis) in pigs in China.

Methods
Five databases (PubMed, ScienceDirect, Chinese Web of Knowledge, Wanfang, and Chongqing VIP) were searched and 50 studies (46,926 domestic pigs, 22 provinces) ultimately identified pertaining to the prevalence of coccidia infection from 1980 to 2019. We incorporated the effect size using the random-effects model in the “meta” package in R software and conducted univariate and multivariate meta-regression analyses using a mixed-effects model.

Results
The pooled prevalence rate of coccidia in pigs was 21.9%, including the C. suis infection rate of 9.1%. The highest prevalence of coccidia (39.6%) was found in northwest China, and this region also presented the lowest prevalence of C. suis (4.7%). In the subgroup analysis based on sampling year, the highest prevalence of coccidia was detected in 2001 or earlier (32.6%), whereas the lowest rate was found in 2012 or later (14.3%). An opposite trend was observed for C. suis (5.5% in 2000 or earlier vs 14.4% in 2000 or later). The prevalence of coccidia in extensive farming systems (29.5%) was higher than that in intensive farming systems (17.3%). In contrast, the point estimate of C. suis prevalence was lower in the extensive farming systems (5.1%) than in the intensive farming systems (10.0%), but the difference was not significant (P > 0.05). Among the four age categories, the highest total coccidia prevalence (26.2%) was found in finishing pigs, followed by suckling piglets (19.9%), whereas the highest prevalence of C. suis (14.9%) was observed in suckling piglets.

Conclusions
Our findings suggest that coccidia infection in Chinese pigs is common, although the prevalence of C. suis in pigs does not receive sufficient attention. We recommend the rational use of anticoccidial drugs to avoid drug resistance and the development of preventive and control measures for C. suis to reduce the incidence of swine coccidiosis.

Graphical Abstract
Human bone marrow-derived, pooled, allogeneic mesenchymal stromal cells manufactured from multiple donors at different times show comparable biological functions in vitro, and in vivo to repair limb ischemia
Authors: Thej Charan , Balasubramanian Sudha , Rengasamy Mathiyazhagan , Walvekar Ankita , Swamynathan Priyanka , Raj Swathi Sundar , Shahani Pradnya , Siddikuzzaman  , Kolkundkar Udaykumar , Seetharam Raviraja N. , Gupta Pawan Kumar , Majumdar Anish S. 
Published: May 2021

Abstract
Background
We have previously demonstrated that a pooled population of bone marrow-derived, allogeneic mesenchymal stromal cells (BMMSC), Stempeucel®-1, produced under good manufacturing practices (GMP) conditions, showed clinical efficacy and safety in patients suffering from critical limb ischemia (CLI) due to Buerger’s disease. While Stempeucel®-1 is currently used for CLI and other clinical indications, we wanted to ensure that the product’s continuity is addressed by developing and characterizing a second generation of pooled product (Stempeucel®-1A), manufactured identically from second BM aspirates of the same three donors after a 2-year interval.

Methods
The two versions of Stempeucel® were manufactured and subjected to gene and protein expression analysis. The nature of various growth factors/cytokines secreted and immunomodulatory activity of these two cell populations were compared directly by various in vitro assays. The preclinical efficacy of these two cell types was compared in an experimental model of hind limb ischemia (HLI) in BALB/c nude mice. The reversal of ischemia, blood flow, and muscle regeneration were determined by functional scoring, laser Doppler imaging, and immunohistochemical analyses.

Results
Qualitative and quantitative analyses of genes and proteins involved in promoting angiogenic activity and immune regulatory functions revealed high levels of correlation between Stempeucel®-1 and Stempeucel®-1A cell populations. Moreover, intramuscular (i.m) administration of these two cell products in the ischemic limbs of BALB/c nude mice showed significant repair (≥ 70%) of toe and foot necrosis, leading to improved ambulatory function and limb salvage. Furthermore, a biodistribution kinetics study showed that Stempeucel®-1 was mostly localized in the ischemic muscles of mice for a significantly longer time compared to normal muscles, thus playing an essential role in modulating and reversing HLI damage.

Conclusions
This study shows that with a reproducible manufacturing procedure, it is possible to generate large numbers of pooled mesenchymal stromal cells from human bone marrow samples to establish product equivalence. We conclude from these results that, for the first time, two pooled, allogeneic BMMSC products can be repeatedly manufactured at different time intervals using a two-tier cell banking process with robust and comparable angiogenic properties to treat ischemic diseases.
LacminCC: lightweight anonymous communication model in cloud computing
Authors: Li Fengyin , Wang Yanli , Ju Hongwei , Yu Xinying , Wang Zhaojie , Zhou Huiyu 
Published: May 2021

AbstractWith increasing application of cloud computing and big data technologies, a large amount of personal information is stored on the Internet, which raises the issue of privacy leakage. To protect people’s data privacy, this paper firstly presents a new anonymous Identify-Based Encryption (IBE) scheme and gives the proof of its security under the Bilinear Diffie–Hellman Security Assumption. Then, by introducing the anonymous IBE scheme into anonymous communication fields, this paper introduces a new lightweight anonymous communication model for cloud computing, which guarantees the anonymity of system users and the security of messages in small groups. Our analysis shows that, the proposed communication model cannot only reduce memory consumption and improve message transmission efficiency, but also effectively resist traffic-analysis attacks, node eavesdropping, and finally achieve secure anonymous communication in cloud computing.
An enhanced binarization framework for degraded historical document images
Authors: Xiong Wei , Zhou Lei , Yue Ling , Li Lirong , Wang Song 
Published: May 2021

AbstractBinarization plays an important role in document analysis and recognition (DAR) systems. In this paper, we present our winning algorithm in ICFHR 2018 competition on handwritten document image binarization (H-DIBCO 2018), which is based on background estimation and energy minimization. First, we adopt mathematical morphological operations to estimate and compensate the document background. It uses a disk-shaped structuring element, whose radius is computed by the minimum entropy-based stroke width transform (SWT). Second, we perform Laplacian energy-based segmentation on the compensated document images. Finally, we implement post-processing to preserve text stroke connectivity and eliminate isolated noise. Experimental results indicate that the proposed method outperforms other state-of-the-art techniques on several public available benchmark datasets.
Outbreaks of healthcare-associated infections linked to water-containing hospital equipment: a literature review
Authors: Yiek Wing-Kee , Coenen Olga , Nillesen Mayke , van Ingen Jakko , Bowles Edmée , Tostmann Alma 
Published: May 2021

AbstractBackgroundHealthcare-associated infections (HAIs) are a significant cause of morbidity and mortality in hospitalized patients. Water in the environment can be a source of infection linked to outbreaks and environmental transmission in hospitals. Water safety in hospitals remains a challenge. This article has summarized available scientific literature to obtain an overview of outbreaks linked to water-containing hospital equipment and strategies to prevent such outbreaks.MethodsWe made a list of water-containing hospital equipment and devices in which water is being used in a semi-closed circuit. A literature search was performed in PubMed with a search strategy containing the names of these medical devices and one or more of the following words: outbreak, environmental contamination, transmission, infection. For each medical device, we summarized the following information: the function of the medical device, causes of contamination, the described outbreaks and possible prevention strategies.ResultsThe following water-containing medical equipment or devices were identified: heater-cooler units, hemodialysis equipment, neonatal incubators, dental unit waterlines, fluid warmers, nebulizers, water traps, water baths, blanketrol, scalp cooling, and thermic stimulators. Of the latter three, no literature could be found. Of all other devices, one or more outbreaks associated with these devices were reported in the literature.ConclusionsThe water reservoirs in water-containing medical devices can be a source of microbial growth and transmissions to patients, despite the semi-closed water circuit. Proper handling and proper cleaning and disinfection can help to reduce the microbial burden and, consequently, transmission to patients. However, these devices are often difficult to clean and disinfect because they cannot be adequately opened or disassembled, and the manufacturer’s cleaning guidelines are often not feasible to execute. The development of equipment without water or fluid containers should be stimulated. Precise cleaning and disinfection guidelines and instructions are essential for instructing healthcare workers and hospital cleaning staff to prevent potential transmission to patients.
Pan-cancer analysis reveals tumor-associated macrophage communication in the tumor microenvironment
Authors: Wang Linbang , He Tao , Liu Jingkun , Tai Jiaojiao , Wang Bing , Chen Zhiyu , Quan Zhengxue 
Published: May 2021

Abstract
Background
Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment (TME). However, their contribution to the immunosuppressive status of the TME remains unclear.

Methods
We integrated single-cell sequencing and transcriptome data from different tumor types to uncover the molecular features of TAMs. In vitro experiments and prospective clinical tests confirmed the results of these analysis.

Results
We first detected intra- and inter-tumoral heterogeneities between TAM subpopulations and their functions, with CD86+ TAMs playing a crucial role in tumor progression. Next, we focused on the ligand-receptor interactions between TAMs and tumor cells in different TME phenotypes and discovered that aberrant expressions of six hub genes, including FLI1, are involved in this process. A TAM-tumor cell co-culture experiment proved that FLI1 was involved in tumor cell invasion, and FLI1 also showed a unique pattern in patients. Finally, TAMs were discovered to communicate with immune and stromal cells.

Conclusion
We determined the role of TAMs in the TME by focusing on their communication pattern with other TME components. Additionally, the screening of hub genes revealed potential therapeutic targets.