bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the effect of perioperative administration of S(+)-ketamine hydrochloride injection for postoperative acute pain in children: study protocol for a prospective, multicenter, randomized, open-label, parallel-group, pragmatic clinical trial
Authors: Wang Hong , Duan Chongyang , Zhang Jianmin , Qu Shuangquan , Sun Ying , Zhou Lizhi , Yang Lujia , Lan Chen , Mi Weidong , Chen Pingyan 
Published: July 2022

Abstract
Background
Inadequate postoperative pain management increases the risk of adverse events after the surgery and aggressive perioperative pain prevention has both short-term and long-term benefits. S(+)-ketamine is an N-methyl-D-aspartic acid (NMDA) receptor antagonist with a strong analgesic effect and can significantly relieve postoperative acute pain and reduce opioid consumption. However, for children, it still needs to be confirmed by large sample clinical studies.

Methods
This is a pragmatic, randomized controlled trial which will evaluate the effect of perioperative administration of S(+)-ketamine hydrochloride injection for postoperative acute pain in children in a pragmatic clinical setting. A total of 3000 children (≤17 years old) undergoing surgery will be included in this protocol. Subjects will be randomized 2:1 to either receive S(+)-ketamine hydrochloride injection or conventional therapy without S(+)-ketamine during the entire perioperative period. The primary endpoints are the area under the receiver operating characteristic (ROC) curve of Face Legs Activity Cry and Consolability (FLACC, 0–7 years old) scale score or Numerical Rating Scale (NRS, 8–17 years old) score within 48 h after surgery, and the consumption of opioids within 48 h after surgery. The secondary endpoints include the time of first use of rescue analgesics after surgery, rescue analgesia rate within 48 h after surgery, anesthesia recovery time, incidence of emergency delirium (for 0-7 years old), changes of anxiety and depression scale scores at 48 h after surgery (for 8-17 years old), incidence of intraoperative adverse events (AEs), and incidence of postoperative AEs and pharmacoeconomic indicators. AEs and serious AEs were recorded to evaluate safety.

Discussion
This trial will be the first pragmatic clinical trial to prospectively assess the effect of perioperative administration of S(+)-ketamine hydrochloride injection for postoperative acute pain in children, which is of great significance to the continuous optimization of clinical anesthesia and analgesia programs for children.

Trial registration
This trial was registered in the U.S. National Institutes of Health ClinicalTrials.gov database (http://clinicaltrials.gov; Registration number: NCT04834427). Registered on 8 April 2021.
Effect of adding a positive memories’ module in a trauma-focused cognitive-behavioural treatment for female survivors of intimate partner violence: trial protocol
Authors: Crespo M. , Miguel-Alvaro A. , Hornillos C. , Sánchez-Ferrer S. , Antón A. A. 
Published: July 2022

AbstractBackgroundTrauma-focused cognitive-behavioural treatments have been proven to be effective for reducing symptoms in female survivors of intimate partner violence (IPV), although they still present some difficulties (e.g. significant drop-out rates, low adherence). Based on existing evidence about the difficulty of accessing memories of positive experiences among these women, we considered integrating positive memory evocation in trauma-focused treatments. The present study aims to test the effect of adding a positive memory module to trauma-focused CBT for female survivors of IPV.MethodsThe study is a single-blind, randomized controlled trial (RCT) comparing two trauma-focused CBT (with and without a positive memory module) for female survivors of IPV and a wait-list condition (superiority trial), including pretreatment and posttreatment measures, and follow-ups at 3, 6 and 12 months. Assessors of treatment outcome will be blinded to the trial arm. We aim to recruit 135 participants who will be randomized to one of the experimental conditions. The primary outcome is PTSD symptom severity. Secondary outcome measures include IPV, attitudes towards IPV, posttraumatic cognitions, centrality of trauma, self-concept, positive and negative affect, depression, anxiety, emotional dysregulation or health-related quality of life, as well as satisfaction with treatment. Moreover, adherence to and satisfaction with treatment will be considered.DiscussionThis study first analyses the effect of including positive memory evocation into a trauma-focused treatment for female survivors of IPV. This strategy aims to improve the effect of the treatments and enhance the healing of the trauma by developing a more integrated and emotionally modulated autobiographical narrative that contributes to the recovery and well-being of the victims.Trial registrationISRCTN73702156. Registered on 10 March 2022.
The validation of a serious game for teaching ultrasound skills
Authors: Olgers T. J. , van Os J. M. , Bouma H. R. , ter Maaten J. C. 
Published: July 2022

Abstract
Background
Point-of-care ultrasound (POCUS) is an important bedside diagnostic tool and is being taught in several specialties. However, mastering the required psychomotor skills takes time and learning curves are different between students. Especially learning to make the right probe movements with the corresponding changes of the ultrasound image on screen, and integrating it into a 3D mental model takes time. This precious bedside-time of trainers and physicians may be reduced using other learning methods for mastering the psychomotor skills, for example the use of serious games. Such a game is under development but it needs to be validated before widespread use can be advised. In this article we describe the development and the first three steps in the validation of a serious game for ultrasound skills.

Results
We have included 18 ultrasound experts and 24 ultrasound novices who played the serious game ‘Underwater” and provided feedback. They concluded that “underwater” is fun to play and that movement of the 3D-printed probe resembled real ultrasound probe movements. Participants highly valued the potential of the game for training eye–hand coordination and stability of probe handling, two very important skills in performing ultrasound in real practice. Although we compared several in-game parameters such as distance and speed, no difference was observed between novices and experts. This means that content- and face validity of the serious game is demonstrated but optimal parameters to measure differences between novices and experts still have to be determined.

Conclusions
Our study shows solid content- and face validity of the serious game “UnderWater” for training ultrasound skills, although construct validity could not be demonstrated yet. The game is appreciated as a promising serious game for training eye–hand coordination and learning ultrasound, which may reduce expensive bed-side teaching.
Physiological and locomotor demands during small-sided games are related to match demands and physical fitness? A study conducted on youth soccer players
Authors: Clemente Filipe Manuel , Silva Ana Filipa , Kawczyński Adam , Yıldız Mehmet , Chen Yung-Sheng , Birlik Sabri , Nobari Hadi , Akyildiz Zeki 
Published: July 2022

Abstract
Aim
The purpose of the study was: (i) to analyze the relationships of physiological and locomotor demands between small-sided games (3v3 and 5v5) and official matches (11v11); (ii) to analyze the relationships between small-sided games demands and the physical fitness of youth soccer players.

Methods
The observational study lasted three weeks. In the first week participants performed the 5v5 (50 × 31 and 40 × 25 m) repeatedly over four days. In the third week they repeatedly performed the 3v3 (39 × 24 and 32 × 19 m) over four consecutive days. Twenty youth soccer players (age: 16.8 ± 0.41) were tested twice for their final velocity at 30–15 Intermittent Fitness test (VIFT), peak speed attained at 30-m sprint test (peak speed), and anaerobic speed reserve (ASR). The heart rate responses and locomotor demands were monitored in the SSGs (3v3 and 5v5) and matches (11v11) occurring once a week. The Polar Team Pro was used as the instrument to monitor heart rate and locomotor demands. Three official matches were also monitored during the period.

Results
Results revealed no significant correlations (p > 0.05) between small-sided games and match physiological or locomotor demands. However, VIFT and ASR were significantly correlated with distance covered at 5v5 (r = 0.483; p = 0.031; and r = − 0.474; p = 0.035, respectively), average speed (r = 0.474; p = 0.035; and r = − 0.453; p = 0.045, respectively), while VIFT was also significantly correlated with distance covered at Z2 intensity (r = 0.510; p = 0.022).

Conclusions
The results suggest that the physiological and locomotor demands occurring in small-sided games are significantly different from those occurring in official matches. Thus, physiological and locomotor similarities between small-sided games and official matches are scarce. Considering the second purpose of this study, the results suggest that VIFT and ASR are important physical fitness parameters to modulate the amount of distance covered by the players in 5v5, the average pace, and also the distance covered at high intensities.
Occupational safety and health aspects of corporate social responsibility reporting in Japan: comparison between 2012 and 2020
Authors: Shimizu Takahiro , Nagata Tomohisa , Fujimoto Ayumi , Inoue Shunsuke , Nagata Masako , Mori Koji 
Published: July 2022

Abstract
Objective
To survey the content of occupational safety and health (OSH) disclosed in corporate social responsibility (CSR)-related reports and integrated reports in 2020 and to compare the changes between 2012 and 2020 according to industry and company size.

Results
Among all companies, 441 (20.3%) issued CSR-related reports and 590 (28.1%) issued integrated reports. The number (percentage) of companies that issued either CSR-related reports or integrated reports was 880 (40.5%). The percentages of both CSR-related reports and integrated reports increased with increased company size. The number (percentage) of companies reporting OSH in CSR-related reports was 391 (88.7%) and that in integrated reports was 493 (83.6%). The percentage of OSH reporting in CSR-related reports and integrated reports was high in secondary industries and low in tertiary industries.
Omental torsion mimicking acute appendicitis in a 7-year-old boy: a case report
Authors: Khalili Elham , Marashi Mahdis , Safarpanah Majid , Majidi Saeedeh , Hesarooeyeh Zahra Ghaeini 
Published: July 2022

Abstract
Background
Torsion of the greater omentum is an uncommon cause of acute abdominal pain. Omental torsion can be divided into primary and secondary. Owing to its nonspecific abdominal pain, preoperative diagnosis is difficult. Ultrasound sonography and abdominal computed tomography scans do not have a major role in preoperative diagnosis. The definite diagnosis is usually made during operation.

Case presentation
A 7-year-old Persian boy was referred with right lower quadrant pain associated with nausea and vomiting. Laboratory blood tests and urinalysis were requested that revealed normal values. Ultrasonography was performed, revealing inflammatory changes with mild free fluid collection in the interloop. The patient underwent an open appendectomy, confirming a normal appendix with omental torsion. Two days later, he was discharged home without postoperative complications.

Conclusions
In patients with acute abdomen, particularly those with acute appendicitis symptoms, omental torsion should be considered in the differential diagnosis.
Organoids: a systematic review of ethical issues
Authors: de Jongh Dide , Massey Emma K. ,   the VANGUARD consortium, Berishvili Ekaterine , Fonseca Laura Mar , Lebreton Fanny , Bellofatto Kevin , Bignard Juliette , Seissler Jochen , Buerck Leila Wolf-van , Honarpisheh Mohsen , Zhang Yichen , Lei Yutian , Pehl Monika , Follenzi Antonia , Olgasi Christina , Cucci Alessia , Borsotti Chiara , Assanelli Simone , Piemonti Lorenzo , Citro Antonio , Pellegrini Silvia , Pignatelli Cataldo , Campo Francesco , Thaunat Olivier , Cronin Antonia J. , Mey Devi , Parisotto Chiara , Rossi Giovanna , Kugelmeier Patrick , Wolint Petra , Mühlemann Markus , Pal-Kutas Karolina , Cavallaro Marco , Götz Julia , Müller Jeanette , Bunnik Eline M. 
Published: July 2022

AbstractOrganoids are 3D structures grown from pluripotent stem cells derived from human tissue and serve as in vitro miniature models of human organs. Organoids are expected to revolutionize biomedical research and clinical care. However, organoids are not seen as morally neutral. For instance, tissue donors may perceive enduring personal connections with their organoids, setting higher bars for informed consent and patient participation. Also, several organoid sub-types, e.g., brain organoids and human–animal chimeric organoids, have raised controversy. This systematic review provides an overview of ethical discussions as conducted in the scientific literature on organoids. The review covers both research and clinical applications of organoid technology and discusses the topics informed consent, commercialization, personalized medicine, transplantation, brain organoids, chimeras, and gastruloids. It shows that further ethical research is needed especially on organoid transplantation, to help ensure the responsible development and clinical implementation of this technology in this field.
Adipose-derived stem cells attenuate acne-related inflammation via suppression of NLRP3 inflammasome
Authors: Li Xiaoxi , Luo Sai , Chen Xinyao , Li Shasha , Hao Lijun , Yang Dan 
Published: July 2022

Abstract
Background
Acne is a chronic facial disease caused by Propionibacterium acnes, which proliferates within sebum-blocked skin follicles and increases inflammatory cytokine production. Several therapeutic drugs and products have been proposed to treat acne, yet no single treatment that ensures long-term treatment efficacy for all patients is available. Here, we explored the use of facial autologous fat transplant of adipose-derived stem cells (ADSCs) to dramatically reduce acne lesions.

Methods
THP-1 cells were treated with active P. acnes for 24 h at different multiplicities of infection, and alterations in inflammatory factors were detected. To study the effect of THP-1 on inflammasome-related proteins, we first co-cultured ADSCs with THP-1 cells treated with P. acnes and evaluated the levels of these proteins in the supernatant. Further, an acne mouse model injected with ADSCs was used to assess inflammatory changes.

Results
Propionibacterium acnes-mediated stimulation of THP-1 cells had a direct correlation with the expression of active caspase-1 and interleukin (IL)-1β in an infection-dependent manner. ADSCs significantly reduced the production of IL-1β induced by P. acnes stimulation through the reactive oxygen species (ROS)/Nod-like receptor family pyrin domain-containing 3 (NLRP3)/caspase-1 pathway. The results showed that ADSCs inhibit the skin inflammation induced by P. acnes by blocking the NLRP3 inflammasome via reducing the secretion of IL-1β in vivo.

Conclusions
Our findings suggest that ADSCs can alter IL-1β secretion by restricting the production of mitochondria ROS, thereby inhibiting the NLRP3/caspase-1 pathway in P. acnes-induced inflammatory responses. This study indicates that anti‐acne therapy can potentially be developed by targeting the NLRP3 inflammasome.
Exosomes from mmu_circ_0001052-modified adipose-derived stem cells promote angiogenesis of DFU via miR-106a-5p and FGF4/p38MAPK pathway
Authors: Liang Zun-Hong , Pan Nan-Fang , Lin Shi-Shuai , Qiu Zhi-Yang , Liang Ping , Wang Jun , Zhang Zhi , Pan Yun-Chuan 
Published: July 2022

AbstractBackgroundDiabetic foot ulcer (DFU) is a chronic infectious disease caused by diabetes mellitus (DM). Angiogenesis plays the decisive role in wound healing of DFU. Adipose-derived stem cells (ADSCs) can ameliorate angiogenesis in DFU by exosomes. This study aims to determine the mechanism of exosomes from mmu_circ_0001052-modified ADSCs in angiogenesis of DFU.MethodsHUVECs were induced by high glucose and mice stimulated using STZ injection during high-fat feeding, which were treated with exosomes derived from mmu_circ_0001052-modified ADSCs. Real-time PCR determined the expression of gene and western blot determined protein levels. Proliferation, migration, apoptosis and angiogenesis of HUVECs were studied by MTT assay, transwell test, flow cytometry and tube formation experiment, respectively. Histological lesion of wound was determined by HE staining.ResultsThe expression of circ_0001052 was upregulated in ADSCs and miR-106a-5p elevated in high glucose-induced HUVECs. Exosomal mmu_circ_0001052 significantly accelerated wound healing in mice with DFU. Also, exosomal mmu_circ_0001052 evoked the reduction of miR-106a-5p and the elevation of FGF4 in high glucose-induced HUVECs and wound tissue of DFU mice. Exosomal mmu_circ_0001052 was determined to sponge miR-106a-5p that targeted FGF4 in DFU. In high glucose-induced HUVECs, exosomal mmu_circ_0001052 inhibited apoptosis and miR-106a-5p expression, and meanwhile promoted proliferation, migration, angiogenesis and expressions of FGF4, VEGF and p-p38/p38, which were reversed by miR-106a-5p elevation.ConclusionMmu_circ_0001052 in ADSCs-derived exosomes promote angiogenesis of DFU via miR-106a-5p and FGF4/p38MAPK pathway.Graphical Abstract
Mesenchymal stem cells derived from adipose accelerate the progression of colon cancer by inducing a MT-CAFs phenotype via TRPC3/NF-KB axis
Authors: Xue Chunling , Gao Yang , Li Xuechun , Zhang Mingjia , Yang Ying , Han Qin , Sun Zhao , Bai Chunmei , Zhao Robert Chunhua 
Published: July 2022

Abstract
Background
There is increasing evidence that mesenchymal stem cells (MSCs) help shape the tumor microenvironment and promote tumor progression, and ion channels might play a critical role in this process. The objective of the present study was to explore the function and mechanism of MT-CAFs on progression of colon cancer.

Methods
Here, a gene chip was used for a general analysis of gene expression changes in MSC-transformed CAF cells (MT-CAFs). Bioinformatic tool and western blot screened out the ion channel protein TRPC3 with significantly increased expression, and identify the function through two-photon microscope. The progression of cancer was detected via MTS, transwell and Wound Healing. ELISA deected the secretion of inflammation factors. TRPC3/NF-KB axis was identified by western blot and immunofluorescence.

Results
TRPC3 can caused calcium influx, which further activated the NF-KB signaling pathway. Knockdown or inhibition of TRPC3 in MSCs significantly reduced the activation of NF-KB, and decreased the growth, migration, and invasion of MT-CAFs. After TRPC3 knockdown, the ability of MT- CAFs to promote tumor migration and invasion was impaired. Conversely, the upregulation of TRPC3 expression in MT-CAFs had the opposite effect. In vivo, TRPC3 expressed on MSCs also contributed to the tumorigenesis and progression of cancer cells. In addition, the Oncomine and GEPIA databases showed that TRPC3 expression is higher in colon cancer tissues compared with normal colon tissues, and was positively correlated with the expression of the CAF genes alpha-smooth muscle (α-SMA/ACTA2) and fibroblast activation protein Alpha. The disease-free survival of patients with positive TRPC3 expression in MSCs was significantly shorter than those with negative expression.

Conclusions
These results indicate that TRPC3 expressed on MT-CAFs plays a critical role in tumor progression via the NF-KB signaling pathway, and is correlated with poor prognosis in colon cancer patients. Therefore, TRPC3 may be a novel therapeutic target for the treatment of colon cancer.
Characterization of cardiac metabolism in iPSC-derived cardiomyocytes: lessons from maturation and disease modeling
Authors: Vučković Sofija , Dinani Rafeeh , Nollet Edgar E. , Kuster Diederik W. D. , Buikema Jan Willem , Houtkooper Riekelt H. , Nabben Miranda , van der Velden Jolanda , Goversen Birgit 
Published: July 2022

Abstract
Background
Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have emerged as a powerful tool for disease modeling, though their immature nature currently limits translation into clinical practice. Maturation strategies increasingly pay attention to cardiac metabolism because of its pivotal role in cardiomyocyte development and function. Moreover, aberrances in cardiac metabolism are central to the pathogenesis of cardiac disease. Thus, proper modeling of human cardiac disease warrants careful characterization of the metabolic properties of iPSC-CMs.

Methods
Here, we examined the effect of maturation protocols on healthy iPSC-CMs applied in 23 studies and compared fold changes in functional metabolic characteristics to assess the level of maturation. In addition, pathological metabolic remodeling was assessed in 13 iPSC-CM studies that focus on hypertrophic cardiomyopathy (HCM), which is characterized by abnormalities in metabolism.

Results
Matured iPSC-CMs were characterized by mitochondrial maturation, increased oxidative capacity and enhanced fatty acid use for energy production. HCM iPSC-CMs presented varying degrees of metabolic remodeling ranging from compensatory to energy depletion stages, likely due to the different types of mutations and clinical phenotypes modeled. HCM further displayed early onset hypertrophy, independent of the type of mutation or disease stage.

Conclusions
Maturation strategies improve the metabolic characteristics of iPSC-CMs, but not to the level of the adult heart. Therefore, a combination of maturation strategies might prove to be more effective. Due to early onset hypertrophy, HCM iPSC-CMs may be less suitable to detect early disease modifiers in HCM and might prove more useful to examine the effects of gene editing and new drugs in advanced disease stages. With this review, we provide an overview of the assays used for characterization of cardiac metabolism in iPSC-CMs and advise on which metabolic assays to include in future maturation and disease modeling studies.