bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of human mitochondrial RNA cleavage sites and candidate RNA processing factors
Authors: Carbajosa Guillermo , Ali Aminah T. , Hodgkinson Alan 
Published: July 2022

Abstract
Background
The human mitochondrial genome is transcribed as long strands of RNA containing multiple genes, which require post-transcriptional cleavage and processing to release functional gene products that play vital roles in cellular energy production. Despite knowledge implicating mitochondrial post-transcriptional processes in pathologies such as cancer, cardiovascular disease and diabetes, very little is known about the way their function varies on a human population level and what drives changes in these processes to ultimately influence disease risk. Here, we develop a method to detect and quantify mitochondrial RNA cleavage events from standard RNA sequencing data and apply this approach to human whole blood data from > 1000 samples across independent cohorts.

Results
We detect 54 putative mitochondrial RNA cleavage sites that not only map to known gene boundaries, short RNA ends and RNA modification sites, but also occur at internal gene positions, suggesting novel mitochondrial RNA cleavage junctions. Inferred RNA cleavage rates correlate with mitochondrial-encoded gene expression across individuals, suggesting an impact on downstream processes. Furthermore, by comparing inferred cleavage rates to nuclear genetic variation and gene expression, we implicate multiple genes in modulating mitochondrial RNA cleavage (e.g. MRPP3, TBRG4 and FASTKD5), including a potentially novel role for RPS19 in influencing cleavage rates at a site near to the MTATP6-COX3 junction that we validate using shRNA knock down data.

Conclusions
We identify novel cleavage junctions associated with mitochondrial RNA processing, as well as genes newly implicated in these processes, and detect the potential impact of variation in cleavage rates on downstream phenotypes and disease processes. These results highlight the complexity of the mitochondrial transcriptome and point to novel mechanisms through which nuclear-encoded genes can potentially influence key mitochondrial processes.
Improvement of several stress response and sleep quality hormones in men and women after sleeping in a bed that protects against electromagnetic fields
Authors: Díaz-Del Cerro E , Félix J , Tresguerres JAF , De la Fuente M 
Published: July 2022

Abstract
Background
The electromagnetic fields (EMFs) emitted by the technologies affect the homeostatic systems (nervous, endocrine, and immune systems) and consequently the health. In a previous work, we observed that men and women, after 2 months of using a bed with a registered HOGO system, that prevents and drain EMFs, improved their immunity, redox and inflammatory states and rejuvenated their rate of aging or biological age. Since, EMFs can act as a chronic stressor stimulus, and affect the sleep quality. The objective of this work was to study in men and women (23–73 years old) the effect of sleeping for 2 months on that bed in the blood concentrations of several hormones related to stress response and sleep quality as well as to corroborate the rejuvenation of their biological age.

Methods
In 18 men and women, plasma concentration of cortisol, dehydroepiandrosterone (DHEA), catecholamines (epinephrine, norepinephrine and dopamine), serotonin, oxytocin and melatonin were analyzed before and after 2 months of using the HOGO beds. A group of 10 people was used as placebo control. In another cohort of 25 men (20 experimental and 5 placebo), the effects of rest on the HOGO system on the concentration of cortisol and testosterone in plasma were studied. In all these volunteers, the biological age was analyzed using the Immunity Clock model.

Results
There is a significant increase in plasma concentration of DHEA, norepinephrine, serotonin, oxytocin, and melatonin as well as in testosterone, after resting for 2 months in that bed with the EMFs avoiding system. In addition, decreases in Cortisol/DHEA and Testosterone/cortisol ratio and plasma dopamine concentration were observed. No differences were found in placebo groups. In all participants that slept on HOGO beds, the biological age was reduced.

Conclusions
Sleeping in a bed that isolates from EMFs and drain them can be a possible strategy to improve the secretion of hormones related to a better response to stress and sleep quality, which means a better endocrine system, and consequently better homeostasis and maintenance of health. This fact was confirmed with the slowdown in the rate of aging checked with a rejuvenation of the biological age.
E3 ubiquitin ligase MAGI3 degrades c-Myc and acts as a predictor for chemotherapy response in colorectal cancer
Authors: Wang Haibo , Yang Wenjing , Qin Qiong , Yang Xiaomei , Yang Ying , Liu Hua , Lu Wenxiu , Gu Siyu , Cao Xuedi , Feng Duiping , Zhang Zhongtao , He Junqi 
Published: July 2022

Abstract
Background
Recurrence and chemoresistance constitute the leading cause of death in colorectal cancer (CRC). Thus, it is of great significance to clarify the underlying mechanisms and identify predictors for tailoring adjuvant chemotherapy to improve the outcome of CRC.

Methods
By screening differentially expressed genes (DEGs), constructing random forest classification and ranking the importance of DEGs, we identified membrane associated guanylate kinase, WW and PDZ domain containing 3 (MAGI3) as an important gene in CRC recurrence. Immunohistochemical and western blot assays were employed to further detect MAGI3 expression in CRC tissues and cell lines. Cell counting kit-8, plate colony formation, flow cytometry, sub-cutaneous injection and azoxymethane plus dextran sulfate sodium induced mice CRC assays were employed to explore the effects of MAGI3 on proliferation, growth, cell cycle, apoptosis, xenograft formation and chemotherapy resistance of CRC. The underlying molecular mechanisms were further investigated through gene set enrichment analysis, quantitative real-time PCR, western blot, co-immunoprecipitation, ubiquitination, GST fusion protein pull-down and immunohistochemical staining assays.

Results
Our results showed that dysregulated low level of MAGI3 was correlated with recurrence and poor prognosis of CRC. MAGI3 was identified as a novel substrate-binding subunit of SKP1-Cullin E3 ligase to recognize c-Myc, and process c-Myc ubiquitination and degradation. Expression of MAGI3 in CRC cells inhibited cell growth, promoted apoptosis and chemosensitivity to fluoropyrimidine-based chemotherapy by suppressing activation of c-Myc in vitro and in vivo. In clinic, the stage II/III CRC patients with MAGI3-high had a significantly good recurrence-free survival (~ 80%, 5-year), and were not necessary for further adjuvant chemotherapy. The patients with MAGI3-medium had a robustly good response rate or recurrence-free survival with fluoropyrimidine-based chemotherapy, and were recommended to undergo fluoropyrimidine-based adjuvant chemotherapy.

Conclusions
MAGI3 is a novel E3 ubiquitin ligase by degradation of c-Myc to regulate CRC development and may act as a potential predictor of adjuvant chemotherapy for CRC patients.

Graphical Abstract
The impact of the COVID-19 pandemic on people who inject drugs accessing harm reduction services in a rural American state
Authors: Thakarar Kinna , Kohut Michael , Hutchinson Rebecca , Bell Rebecca , Loeb Hannah E. , Burris Debra , Fairfield Kathleen M. 
Published: July 2022

Abstract
Background
The impact of public health policies during the COVID-19 pandemic on people who inject drugs (PWID) has varied across regions. In other countries, recent research has shown that PWID access to harm reduction services, despite rapid adaptations, has been negatively impacted. Our study describes these impacts in a rural state.

Methods
We conducted semi-structured interviews with PWID, community partners, and healthcare providers in the rural state of Maine (USA). We explored how changes made during the pandemic impacted access to harm reduction services, including basic services (i.e., shelter), syringe service programs, safe drug supply, low barrier treatment, and peer support. Interviews were analyzed using the framework method to apply Penchansky’s model of access, with Saurman’s modification, which includes six dimensions of access—accessibility, availability, acceptability, affordability, accommodation, awareness.

Results
We interviewed thirty-six stakeholders (N = 9 community partners, N = 9 healthcare providers, N = 18 PWID). Policies such as mobile outreach expansion, mail delivery of equipment, and relaxed telemedicine regulations facilitated accessibility to syringe service programs and low barrier buprenorphine treatment. Public health policies, such as social distancing and screening policies, reduced contact, which subsequently reduced acceptability and awareness of many services. Elimination of the one-for-one needle exchange in some areas increased, acceptability (i.e., perception of service), and affordability for PWID. However, some areas actually began enforcing a one-for-one needle exchange policy, which reduced affordability, acceptability, and awareness of services.

Conclusions
Changes resulting from the COVID-19 pandemic have impacted all dimensions of access to harm reduction services among PWID. While some barriers to harm reduction services were unavoidable during the pandemic, we found that specific policy decisions mitigated service barriers, while other policies exacerbated them. Relaxing needle exchange policies were particularly helpful in facilitating access to harm reduction services by giving community organizations flexibility to adapt to the evolving needs of PWID. These results can inform policies and service delivery to optimally mitigate the negative impacts on PWID during, and beyond, the pandemic.
Validity and reliability of the Persian version of the short-form child perceptions questionnaire 11–14-year-old children (CPQ11–14)
Authors: Baherimoghadam Tahereh , Hamedani Shahram , Naseri Navid , Ghafoori Alireza 
Published: July 2022

Abstract
Background
The Child Perception questionnaire 11–14 (CPQ 11–14) is an efficient tool for assessment of oral health-related quality of life (OHRQoL). This questionnaire has been briefed to 16 items (CPQ11–14 ISF-16) to facilitate its employment. The purpose the present study was to translate CPQ11–14 ISF-16 to Persian language, culturally adapt, and initially evaluate its among adolescent population.

Material and method
The questionnaire has been translated to Persian, then back-translated to English, and finally underwent cultural adaptation and pretesting assessment. It was then filled out by 318 participents (175 grils and 143 boys), with the age of 11 to 14 years resident in Shiraz, Iran. The Persian version of CPQ11–14 ISF-16 along with the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) and two suggested global questions were administered among participants to assess its criterion validity.

Results
The factor analysis extracted two domains and the factor loading of domains ranged from 0.423 to 0.837. Persian version of CPQ11–14 ISF-16 presented high internal consistency (Cronbach’s alpha = 0.854), and showed excellent criterion validity with PIDAQ (rho = 0.731, p < 0.001). There was a statistically significant positive moderate correlation between CPQ11–14 ISF-16 and its factors 1 and 2 and two global questions (first global question: rho = 0.439, p < 0.001; second global question: rho = 0.457, p = 0.035).

Conclusion
The Persian version of CPQ11–14 ISF-16 has optimal validity and reliability in a general population of 11–14-year-old Persian children.
Aboriginal and Torres Strait Islander Peoples' perceptions of foot and lower limb health: a systematic review
Authors: Sadler Sean , Gerrard James , West Matthew , Lanting Sean , Charles James , Searle Angela , Chuter Vivienne 
Published: July 2022

AbstractBackgroundOngoing colonisation produces inequity in healthcare delivery and inequality in healthcare outcomes for Aboriginal and Torres Strait Islander Peoples. As a consequence, within the domain of lower limb health, foot disease has severe impacts for First Nations Peoples. Central to developing culturally safe healthcare and driving positive foot health change for First Nations Peoples, is the need for health professionals to develop understanding of First Nations perspectives of foot health. The aim of this systematic review was to evaluate studies investigating Aboriginal and Torres Strait Islander Peoples' perceptions of foot and lower limb health.MethodsPubMeD, Ovid (Embase, Emcare, Medline), CINAHL, Informit Indigenous collection, and grey literature sources were searched to 23rd July 2021. We included any published reports or studies that examined Aboriginal and Torres Strait Islander Peoples' perceptions of foot and lower limb health, or meanings of, or attitudes to, foot and lower limb health.ResultsFour studies with a total of 1515 participants were included. Studies found that Aboriginal and Torres Strait Islander people self‐assessed foot health with a demonstrated ability to perceive their feet as healthy relative to Western clinical measures of peripheral blood supply and neurological function. Footwear, including ill‐fitting or lack of footwear was considered a contributing factor to reduced foot and lower limb health. Foot pain affected up to 60% of participants with up to 70% of foot pain untreated. Lack of access to culturally safe health care delivered by culturally capable health professionals was perceived to contribute to worse foot and lower limb health outcomes.ConclusionsAboriginal and Torres Strait Islander Peoples' perceptions of foot and lower limb health are influenced by multiple complex interrelated factors. The limited number of studies in this area indicates ongoing failings to consult First Nations Peoples regarding their own lower limb and foot health. It is therefore essential that healthcare service and cultural capability implementation is led by Aboriginal and Torres Strait Islander Peoples in co‐design. Urgent need for further research that exemplifies design and delivery of culturally safe care is required.
NeuroSAFE PROOF: study protocol for a single-blinded, IDEAL stage 3, multi-centre, randomised controlled trial of NeuroSAFE robotic-assisted radical prostatectomy versus standard robotic-assisted radical prostatectomy in men with localized prostate cancer
Authors: Dinneen Eoin , Grierson Jack , Almeida-Magana Ricardo , Clow Rosie , Haider Aiman , Allen Clare , Heffernan-Ho Daniel , Freeman Alex , Briggs Tim , Nathan Senthil , Mallett Susan , Brew-Graves Chris , Muirhead Nicola , Williams Norman R. , Pizzo Elena , Persad Raj , Aning Jon , Johnson Lyndsey , Oxley Jon , Oakley Neil , Morgan Susan , Tahir Fawzia , Ahmad Imran , Dutto Lorenzo , Salmond Jonathan M. , Kelkar Anand , Kelly John , Shaw Greg 
Published: July 2022

Abstract
Background
Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients’ quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM.

Methods
NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life.

Discussion
NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world.

Trial registration
NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978.
Myometrial oxidative stress drives MED12 mutations in leiomyoma
Authors: Li Yinuo , Xu Xiuhua , Asif Huma , Feng Yue , Kohrn Brendan F. , Kennedy Scott R. , Kim J. Julie , Wei Jian-Jun 
Published: July 2022

Abstract
Background
More than 70% of leiomyomas (LM) harbor MED12 mutations, primarily in exon 2 at c.130-131(GG). The cause of MED12 mutations in myometrial cells remains largely unknown. We hypothesized that increased ROS promotes MED12 mutations in myometrial cells through the oxidation of guanine nucleotides followed by misrepair.

Methods
Genomic oxidative burden (8-OHdG) was evaluated in vitro and in vivo by immunohistochemistry. MED12 mutations were examined by Sanger sequencing and deep sequencing. Transcriptome examined by RNA-seq was performed in myometrium with and without LM, in primary myometrial cells treated with ROS. 8-OHdG mediated misrepair was analyzed by CRISPR/Cas9.

Results
Uteri with high LM burden had a significantly higher rate of MED12 mutations than uteri with low LM burden. Compelling data suggest that the uterus normally produces reactive oxidative species (ROS) in response to stress, and ROS levels in LM are elevated due to metabolic defects. We demonstrated that genomic oxidized guanine (8-OHdG) was found at a significantly higher level in the myometrium of uteri that had multiple LM compared to myometrium without LM. Transcriptome and pathway analyses detected ROS stress in myometrium with LM. Targeted replacement of guanine with 8-OHdG at MED12 c.130 by CRISPR/Cas9 significantly increased the misrepair of G>T. Exposure of primary myometrial cells to oxidative stress in vitro increased misrepair/mutations as detected by duplex sequencing.

Conclusions
Together, our data identified a clear connection between increased myometrial oxidative stress and a high rate of MED12 mutations that may underlie the risk of LM development and severity in women of reproductive age.

Graphical Abstract
R&D of a low-complexity OFDM acoustic communication payload for Micro-AUV in confined space
Authors: Jiang Weihua , Tao Qiuyang , Yao Junhui , Tong Feng , Zhang Fumin 
Published: July 2022

AbstractWith small size, high flexibility, low cost, and deployment convenience, Micro-sized autonomous underwater vehicle (Micro-AUV) is capable of performing diverse underwater missions efficiently in confined underwater space, for the extensive purpose of rescue, sightseeing, pipeline engineering and so on. The underwater acoustic (UWA) communication technique provides an effective way to support this types of underwater mission for telemetry and remote control of Micro-AUV. However, while the adverse multipath caused by confined space poses significant challenge to the classic coherent acoustic communication schemes that need channel estimation and equalization processing, the employment of non-coherent communication scheme is generally limited by low data rate. By utilizing time-domain and frequency-domain differential modulation to suppress the influence of multipath, a low-complexity UWA communication payload is designed to provide an effective solution to make a tradeoff between data rate and implementation complexity. Based on a STM32 series processor, this paper introduced the software and hardware implementation of a time-frequency differential OFDM UWA communication payload for Micro-AUV and presented the performance evaluation of the system in confined underwater space. The experimental results achieved in a confined lake show that the proposed system has the potential of being used for Micro-AUV to achieve a data rate of 1.96 kbps at a distance of 200m with acceptable implementation overhead.
Development of uniform food information –the case of front of package nutrition labels in the EU
Authors: Bottari Federico , Mark-Herbert Cecilia 
Published: July 2022

AbstractThe current malnutrition epidemic calls for actions. Current practices in the EU show a variety of communication efforts but the international character of food markets call for a harmonized language. The aim of the project is to identify the themes in the on-going debate regarding the development of a single front-of-package nutrition label in the European Union. A case study approach was used, focusing on the positions of different key stakeholders in Sweden and Italy. Overarching EU-perspectives, European Commission and European Council of Ministries were also included. Collected data from semi-structured interviews and strategic documents were used in a thematic content analysis. The results show that the stakeholders are influencing the process towards contradicting outcomes. Different stakeholders argue for opposing ideal labelling schemes, while still agreeing on the need for a harmonization. Major disagreements arise on whether the label should be voluntary or not, based on portion or 100 g and on the ideal label design. Stakeholders’ positions depend on food system role and previous experience of this type of labelling. The internal political debate in the European Union is still at an early stage and consensus has not been reached due to diverging views. The patterns that emerge from the analysis of the different point of views can facilitate the cooperation between stakeholders and policy-makers.
Identification of phenylketonuria patient genotypes using single-gene full-length sequencing
Authors: Gao Jinshuang , Li Xiaole , Guo Yaqing , Yu Haiyang , Song Liying , Fang Yang , Yuan Erfeng , Shi Qianqian , Zhao Dehua , Yuan Enwu , Zhang Linlin 
Published: July 2022

Abstract
Background
Phenylketonuria (PKU) is a common, autosomal recessive inborn error of metabolism caused by PAH gene variants. After routine genetic analysis methods were applied, approximately 5% of PKU patients were still not diagnosed with a definite genotype.

Methods
In this study, for the first time, we identified PKU patients with unknown genotypes via single-gene full-length sequencing.

Results
The detection rate of PKU genotype increased from 94.6 to 99.4%, an increase of approximately 5%. The variants c.1199 + 502A > T and 1065 + 241C > A were found at a high frequency in Chinese PKU patients.

Conclusion
Our study suggest that single-gene full-length sequencing is a rapid, efficient and cost-effective tool to improve the genotype detection rate of PKU patients. Moreover, we provides additional case data to support pathogenicity of deep intronic variants in PAH.