bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle miRNAs are influenced by sex at baseline and in response to exercise
Authors: Hiam Danielle , Landen Shanie , Jacques Macsue , Voisin Sarah , Lamon Séverine , Eynon Nir 
Published: November 2023

Abstract
Background
Sex differences in microRNA (miRNA) expression profiles have been found across multiple tissues. Skeletal muscle is one of the most sex-biased tissues of the body. MiRNAs are necessary for development and have regulatory roles in determining skeletal muscle phenotype and have important roles in the response to exercise in muscle. Yet there is limited research into the role and regulation of miRNAs in the skeletal muscle at baseline and in response to exercise, a well-known modulator of miRNA expression. The aim of this study was to investigate the effect of sex on miRNA expression in the skeletal muscle at baseline and after an acute bout of high-intensity interval exercise. A total of 758 miRNAs were measured using Taqman®miRNA arrays in the skeletal muscle of 42 healthy participants from the Gene SMART study (23 males and 19 females of comparable fitness levels and aged 18–45 years), of which 308 were detected. MiRNAs that differed by sex at baseline and whose change in expression following high-intensity interval exercise differed between the sexes were identified using mixed linear models adjusted for BMI and Wpeak. We performed in silico analyses to identify the putative gene targets of the exercise-induced, sex-specific miRNAs and overrepresentation analyses to identify enriched biological pathways. We performed functional assays by overexpressing two sex-biased miRNAs in human primary muscle cells derived from male and female donors to understand their downstream effects on the transcriptome.

Results
At baseline, 148 miRNAs were differentially expressed in the skeletal muscle between the sexes. Interaction analysis identified 111 miRNAs whose response to an acute bout of high-intensity interval exercise differed between the sexes. Sex-biased miRNA gene targets were enriched for muscle-related processes including proliferation and differentiation of muscle cells and numerous metabolic pathways, suggesting that miRNAs participate in programming sex differences in skeletal muscle function. Overexpression of sex-biased miRNA-30a and miRNA-30c resulted in profound changes in gene expression profiles that were specific to the sex of the cell donor in human primary skeletal muscle cells.

Conclusions
We uncovered sex differences in the expression levels of muscle miRNAs at baseline and in response to acute high-intensity interval exercise. These miRNAs target regulatory pathways essential to skeletal muscle development and metabolism. Our findings highlight that miRNAs play an important role in programming sex differences in the skeletal muscle phenotype.
Anti-TIM3 chimeric antigen receptor-natural killer cells from engineered induced pluripotent stem cells effectively target acute myeloid leukemia cells
Authors: Klaihmon Phatchanat , Luanpitpong Sudjit , Kang Xing , Issaragrisil Surapol 
Published: November 2023

Abstract
Background
Acute myeloid leukemia (AML) is a clonal malignant disorder which originates from a small number of leukemia-initiating cells or leukemic stem cells (LSCs)—the subpopulation that is also the root cause of relapsed/refractory AML. Chimeric antigen receptor (CAR)-T cell therapy has proved successful at combating certain hematologic malignancies, but has several hurdles that limit its widespread applications. CAR-natural killer (NK) cells do not carry the risk of inducing graft-versus-host disease (GvHD) frequently associated with allogeneic T cells, thereby overcoming time-consuming, autologous cell manufacturing, and have relatively safer clinical profiles than CAR-T cells. The present study aimed to generate anti-TIM3 CAR-NK cells targeting LSCs from a clonal master induced pluripotent stem cells engineered with the third-generation anti-TIM3 CAR.

Methods
A clonal master umbilical cord blood NK-derived induced pluripotent stem cell (iPSC) line, MUSIi013-A, was used as a starting cells for engineering of an anti-TIM3 CAR harboring TIM3 scFv fragment (clone TSR-022), CD28, 4-1BB, and CD3ζ signaling (CAR-TIM3). The established CAR-TIM3 iPSCs were further differentiated under serum- and feeder-free conditions into functional CAR-TIM3 NK cells and tested for its anti-tumor activity against various TIM3-positive AML cells.

Results
We successfully established a single-cell clone of CAR-TIM3 iPSCs, as validated by genomic DNA sequencing as well as antibody and antigen-specific detection. We performed thorough iPSC characterization to confirm its retained pluripotency and differentiation capacity. The established CAR-TIM3 iPSCs can be differentiated into CAR-TIM3 NK-like cells, which were further proven to have enhanced anti-tumor activity against TIM3-positive AML cells with minimal effect on TIM3-negative cells when compared with wild-type (WT) NK-like cells from parental iPSCs.

Conclusions
iPSCs engineered with CARs, including the established single-cell clone CAR-TIM3 iPSCs herein, are potential alternative cell source for generating off-the-shelf CAR-NK cells as well as other CAR-immune cells. The feasibility of differentiation of functional CAR-TIM3 NK cells under serum- and feeder-free conditions support that Good Manufacturing Practice (GMP)-compliant protocols can be further established for future clinical applications.
Health workers’ adherence to the malaria test, treat and track strategy during the COVID-19 pandemic in malaria high transmission area in Eastern Uganda
Authors: Mumali Richard Kabaka , Okolimong Charles , Kabuuka Tonny , Lubaale Yovani Moses , Okibure Ambrose , Okello Francis , Soita David , Olupot-Olupot Peter 
Published: November 2023

Abstract
Background
Coronavirus disease 2019 (COVID-19) pandemic affected malaria control activities in sub-Saharan Africa (SSA) resulting in 690,000 excess deaths in the year 2021. The authors hypothesized that COVID-19 affected the World Health Organization (WHO) Test, Treat and Track (T3) strategy that has been implemented in Uganda since 2010. In this study, health worker’s adherence to the T3 strategy during COVID-19 pandemic in Eastern Uganda was studied by assessing their knowledge, skills and practices.

Methods
A cross-sectional study utilizing mixed quantitative and qualitative data collections methods was conducted at Mbale Regional Referral Hospital in Eastern Uganda between November and December in 2020. Data were captured on demographics, knowledge, skills and practices for both health workers (HWs) and patients. Quantitative data were analysed using STATA 15.0 and reported as descriptive statistics, proportions and statistical associations. Moreover, qualitative data were collected via key informant interviews (KII) among purposively sampled study participants and analysed thematically using NVIVO software. Ethical approval was obtained prior to the study.

Results
A total of 436 study participants, of whom 103/436 (24%) and 333/436 (76%) were HWs and patients, respectively were studied. Among the HWs with mean age of 34 years (SD = 8.8 years), 81/103 (79%) had good practices, most 63/103 (61%) had good knowledge, and only 11/103 (10.7%) had good skills. Specifically, on the cadres, the laboratory personnel 19/103 (18%) had good knowledge 14/19 (74%) OR: 2.0 (95% CI 0.7–6) and were highly skilled OR: 4.6 (95% CI 1.2—18.1; P < 0.0150) compared to other cadres, respectively. Among the patients whose age ranged 3 months to 80 years (mean 17.8 years) and females 177/333 (53%); a majority 257/333 (77%) were tested, of whom 139/333 (42%) tested positive. Out of the positive cases, 115/333 (35%) were treated and tracked. About 75/333 (23%) were not tested but treated for malaria. Of the 168/239 (70.3%) patients tested, 115/168 (68.5%) were positive and treated, P = 0.0001. The KII revealed low level of In-service training, overwhelming number of patients and stock-out of supplies as a key factor for poor HW adherence to T3 strategy.

Conclusions
During COVID-19 pandemic period HWs adherence to T3 initiative was low as 27% malaria patients did not receive treatment.
LINC02086 promotes cell viability and inhibits cell apoptosis in breast cancer by sponging miR-6757-5p and up-regulating EPHA2
Authors: Han Xue , Shi Fan , Guo Shujun , Li Yao , Wang Hongtao , Song Chuanwang , Wu Shiwu 
Published: November 2023

Abstract
Background
Long non-coding RNAs (lncRNAs) are critical regulators in the initiation and progression of breast cancer. Our study aims to characterize the functions of LINC02086 which few published in breast cancer and decipher the downstream molecular mechanisms.

Methods
LINC02086 expression is tested in RNA-seq data from GEPIA database, tumor tissue samples from hospital patients and breast cancer cell lines. LINC02086 was silenced or overexpressed by lenti-virus-mediated shRNAs, or pLVX-Puro plasmids. Luciferase reporter assay and RNA pull-down assay were applied to study interactions between LINC02086, miR-6757-5p and ephrin type-A receptor 2 (EPHA2). LINC02086-silencing MCF-7 cells were injected into mice to establish xenograft animal models.

Results
Using RNA-seq data, tumor tissue samples and breast cancer cells, LINC02086 was consistently found to be up-regulated in breast cancer, and correlated with poorer prognosis. LINC02086 knockdown decreased cell viability, promoted cell apoptosis and suppressed tumor growth. LINC02086 interacted with miR-6757-5p that interacted with EPHA2.LINC02086 expression was negatively correlated with miR-6757-5p expression (r = -0.5698, P < 0.001) but was positively correlated with EPHA2 expression (r = 0.5061, P < 0.001). miR-6757-5p expression was negatively correlated with EPHA2 expression (r = -0.5919, P < 0.001). LINC02086 regulated EPHA2 via miR-6757-5p. miR-6757-5p/EPHA2 axis was a mediator of the effect of LINC02086 on cell viability and apoptosis.

Conclusion
LINC02086 increases cell viability and decreases apoptotic cells in breast cancer by sponging miR-6757-5p to upregulate EPHA2. This study presents LINC02086/miR-6757-5p/EPHA2 axis as promising therapeutic targets for breast cancer intervention.
Research- vs. government-driven physical activity policy monitoring: a systematic review across different levels of government
Authors: Messing Sven , Tcymbal Antonina , Abu-Omar Karim , Gelius Peter 
Published: November 2023

Abstract
Background
Even though the importance of physical activity policy monitoring has increased in the last decade, there is a lack of understanding what different approaches exist and which methodology they employ. In order to address this research gap, this review attempts to map existing approaches of physical activity policy monitoring and to analyse methodological aspects, especially with regards to the roles of governments and researchers.

Methods
A systematic search was conducted in five scientific databases (PubMed, Scopus, SportDiscus, Psycinfo, Web of Knowledge) in July 2021, and the identified records were screened independently by two reviewers. Records were included if they (a) focused on the monitoring of public policies to promote PA, (b) allowed to compare policies across time, across nations/regions or across policy sectors, and (c) were written in English, German or Russian. During full text analysis, information on methodological aspects was extracted and studies were categorized based on the level of government involvement.

Results
The search yielded in a total of 112 studies. 86 of these studies (76.8%) followed a research-driven approach (little or no government involvement) while only two studies (1.8%) were based on a government-driven approach (led by governments). The remaining 24 studies (21.4%) were based on a co-production approach (strong collaboration between researchers and governments). All in all, 18 different tools for physical activity policy monitoring were identified; key examples are the Report Cards on Physical Activity for Children and Youth (research-driven approach), the HEPA Monitoring Framework (government-driven approach) and the HEPA Policy Audit Tool (co-production approach).

Conclusions
The level of government involvement in policy monitoring differs significantly, and research-driven, government-driven and co-production approaches can be distinguished. These approaches have different strengths and weaknesses, and can be linked to distinct theories of change and models on research-policy relations. Increasing awareness on the implications of these approaches is key to improve the understanding and further development of physical activity policy monitoring.
Conceptualising the value of simulation modelling for public engagement with policy: a critical literature review
Authors: Loblay Victoria , Freebairn Louise , Occhipinti Jo-An 
Published: November 2023

AbstractAs we face complex and dynamically changing public health and environmental challenges, simulation modelling has come to occupy an increasingly central role in public engagements with policy. Shifts are occurring not only in terms of wider public understandings of modelling, but also in how the value of modelling is conceptualised within scientific modelling communities. We undertook a critical literature review to synthesise the underlying epistemic, theoretical and methodological assumptions about the role and value of simulation modelling within the literature across a range of fields (e.g., health, social science and environmental management) that engage with participatory modelling approaches. We identified four cross-cutting narrative conceptualisations of the value of modelling across different research traditions: (1) models simulate and help solve complex problems; (2) models as tools for community engagement; (3) models as tools for consensus building; (4) models as volatile technologies that generate social effects. Exploring how these ideas of ‘value’ overlap and what they offer one another has implications for how participatory simulation modelling approaches are designed, evaluated and communicated to diverse audiences. Deeper appreciation of the conditions under which simulation modelling can catalyse multiple social effects is recommended.
The novel norcantharidin derivative DCZ5417 suppresses multiple myeloma progression by targeting the TRIP13–MAPK–YWHAE signaling pathway
Authors: Wang Yingcong , Dong Sanfeng , Hu Ke , Xu Li , Feng Qilin , Li Bo , Wang Guangli , Chen Gege , Zhang Bibo , Jia Xinyan , Xu Zhijian , Gao Xuejie , Zhang Hui , Xie Yongsheng , Lu Meiling , Chang Shuaikang , Song Dongliang , Wu Xiaosong , Jia Qi , Zhu Huabin , Zhou Jinfeng , Zhu Weiliang , Shi Jumei 
Published: November 2023

Abstract
Background
Multiple myeloma (MM), an incurable disease owing to drug resistance, requires safe and effective therapies. Norcantharidin (NCTD), an active ingredient in traditional Chinese medicines, possesses activity against different cancers. However, its toxicity and narrow treatment window limit its clinical application. In this study, we synthesized a series of derivatives of NCTD to address this. Among these compounds, DCZ5417 demonstrated the greatest anti-MM effect and fewest side effects. Its anti-myeloma effects and the mechanism were further tested.

Methods
Molecular docking, pull-down, surface plasmon resonance-binding, cellular thermal shift, and ATPase assays were used to study the targets of DCZ5417. Bioinformatic, genetic, and pharmacological approaches were used to elucidate the mechanisms associated with DCZ5417 activity.

Results
We confirmed a highly potent interaction between DCZ5417 and TRIP13. DCZ5417 inhibited the ATPase activity of TRIP13, and its anti-MM activity was found to depend on TRIP13. A mechanistic study verified that DCZ5417 suppressed cell proliferation by targeting TRIP13, disturbing the TRIP13/YWHAE complex and inhibiting the ERK/MAPK signaling axis. DCZ5417 also showed a combined lethal effect with traditional anti-MM drugs. Furthermore, the tumor growth-inhibitory effect of DCZ5417 was demonstrated using in vivo tumor xenograft models.

Conclusions
DCZ5417 suppresses MM progression in vitro, in vivo, and in primary cells from drug-resistant patients, affecting cell proliferation by targeting TRIP13, destroying the TRIP13/YWHAE complex, and inhibiting ERK/MAPK signaling. These results imply a new and effective therapeutic strategy for MM treatment.
Hypothermia combined with extracellular vesicles from clonally expanded immortalized mesenchymal stromal cells improves neurodevelopmental impairment in neonatal hypoxic-ischemic brain injury
Authors: Labusek Nicole , Ghari Parnian , Mouloud Yanis , Köster Christian , Diesterbeck Eva , Hadamitzky Martin , Felderhoff-Müser Ursula , Bendix Ivo , Giebel Bernd , Herz Josephine 
Published: November 2023

Abstract
Background
Neonatal encephalopathy following hypoxia–ischemia (HI) is a leading cause of childhood death and morbidity. Hypothermia (HT), the only available but obligatory therapy is limited due to a short therapeutic window and limited efficacy. An adjuvant therapy overcoming limitations of HT is still missing. Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have shown promising therapeutic effects in various brain injury models. Challenges associated with MSCs’ heterogeneity and senescence can be mitigated by the use of EVs from clonally expanded immortalized MSCs (ciMSCs). In the present study, we hypothesized that intranasal ciMSC-EV delivery overcomes limitations of HT.

Methods
Nine-day-old C57BL/6 mice were exposed to HI by occlusion of the right common carotid artery followed by 1 h hypoxia (10% oxygen). HT was initiated immediately after insult for 4 h. Control animals were kept at physiological body core temperatures. ciMSC-EVs or vehicle were administered intranasally 1, 3 and 5 days post HI/HT. Neuronal cell loss, inflammatory and regenerative responses were assessed via immunohistochemistry, western blot and real-time PCR 7 days after insult. Long-term neurodevelopmental outcome was evaluated by analyses of cognitive function, activity and anxiety-related behavior 5 weeks after HI/HT.

Results
In contrast to HT monotherapy, the additional intranasal therapy with ciMSC-EVs prevented HI-induced cognitive deficits, hyperactivity and alterations of anxiety-related behavior at adolescence. This was preceded by reduction of striatal neuronal loss, decreased endothelial, microglia and astrocyte activation; reduced expression of pro-inflammatory and increased expression of anti-inflammatory cytokines. Furthermore, the combination of HT with intranasal ciMSC-EV delivery promoted regenerative and neurodevelopmental processes, including endothelial proliferation, neurotrophic growth factor expression and oligodendrocyte maturation, which were not altered by HT monotherapy.

Conclusion
Intranasal delivery of ciMSC-EVs represents a novel adjunct therapy, overcoming limitations of acute HT thereby offering new possibilities for improving long-term outcomes in neonates with HI-induced brain injury.
Heart transplantation surgery in children and young adults with congenital heart disease
Authors: Martens Sabrina , Tie Hongtao , Kehl Hans Gerd , Tjan Tonny DT , Scheld Hans Heinrich , Martens Sven , Hoffmeier Andreas 
Published: November 2023

Abstract
Background
Pediatric cardiac transplantation remains a surgical challenge as a variety of cardiac and vessel malformation are present in patients with congenital heart disease (CHD). Despite limited availability and acceptability of donor hearts, the number of heart transplantations remains on a stable level with improved survival and quality of life.

Observation
As treatment options for CHD continue to improve and the chances of survival increase, more adult CHD patients are listed for transplantation. This review focuses on the clinical challenges and modified techniques of pediatric heart transplantations.

Conclusion
Not only knowledge of the exact anatomy, but above all careful planning, interdisciplinary cooperation and surgical experience are prerequisites for surgical success.
Effects of early versus delayed application of prone position on ventilation–perfusion mismatch in patients with acute respiratory distress syndrome: a prospective observational study
Authors: Yuan Xueyan , Zhao Zhanqi , Chao Yali , Chen Dongyu , Chen Hui , Zhang Rui , Liu Songqiao , Xie Jianfeng , Yang Yi , Qiu Haibo , Heunks Leo , Liu Ling 
Published: November 2023

Abstract
Background
Prone position has been shown to improve oxygenation and survival in patients with early acute respiratory distress syndrome (ARDS). These beneficial effects are partly mediated by improved ventilation/perfusion (V/Q) distribution. Few studies have investigated the impact of early versus delayed proning on V/Q distribution in patients with ARDS. The aim of this study was to assess the regional ventilation and perfusion distribution in early versus persistent ARDS after prone position.

Methods
This is a prospective, observational study from June 30, 2021, to October 1, 2022 at the medical ICU in Zhongda Hospital, Southeast University. Fifty-seven consecutive adult patients with moderate-to-severe ARDS ventilated in supine and prone position. Electrical impedance tomography was used to study V/Q distribution in the supine position and 12 h after a prone session.

Results
Of the 57 patients, 33 were early ARDS (≤ 7 days) and 24 were persistent ARDS (> 7 days). Oxygenation significantly improved after proning in early ARDS (157 [121, 191] vs. 190 [164, 245] mm Hg, p < 0.001), whereas no significant change was found in persistent ARDS patients (168 [136, 232] vs.177 [155, 232] mm Hg, p = 0.10). Compared to supine position, prone reduced V/Q mismatch in early ARDS (28.7 [24.6, 35.4] vs. 22.8 [20.0, 26.8] %, p < 0.001), but increased V/Q mismatch in persistent ARDS (23.8 [19.8, 28.6] vs. 30.3 [24.5, 33.3] %, p = 0.006). In early ARDS, proning significantly reduced shunt in the dorsal region and dead space in the ventral region. In persistent ARDS, proning increased global shunt. A significant correlation was found between duration of ARDS onset to proning and the change in V/Q distribution (r = 0.54, p < 0.001).

Conclusions
Prone position significantly reduced V/Q mismatch in patients with early ARDS, while it increased V/Q mismatch in persistent ARDS patients.
Trial registration ClinicalTrials.gov (NCT05207267, principal investigator Ling Liu, date of registration 2021.08.20).
Low-complexity enhancement VVC encoder for vehicular networks
Authors: Jiang Xiantao , Li Wei , Song Tian 
Published: November 2023

AbstractIn intelligent transportation systems, real-time video streaming via vehicle networks has been seen as a vital difficulty. The goal of this paper is to decrease the computational complexity of the versatile video coding (VVC) encoder for VANETs. In this paper, a low-complexity enhancement VVC encoder is designed for vehicular communication. First, a fast coding unit (CU) partitioning scheme based on CU texture features is proposed in VVC, which aims to decide the final type of CU partition by calculating CU texture complexity and gray-level co-occurrence matrix (GLCM). Second, to reduce the number of candidate prediction mode types in advance, a fast chroma intra-prediction mode optimization technique based on CU texture complexity aims to combine intra-prediction mode features. Moreover, the simulation outcomes demonstrate that the overall approach may substantially reduce encoding time, while the loss of coding efficiency is reasonably low. The encoding time can be reduced by up to 53.29% when compared to the VVC reference model, although the average BD rate is only raised by 1.26%. The suggested VVC encoder is also hardware-friendly and has a minimal level of complexity for video encoders used in connected vehicle applications.