bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol use, intimate partner violence, and HIV sexual risk behavior among young people in fishing communities of Lake Victoria, Uganda
Authors: Wandera Stephen Ojiambo , Tumwesigye Nazarius Mbona , Walakira Eddy J. , Kisaakye Peter , Wagman Jennifer 
Published: March 2021

Abstract
Background
Few studies have investigated the association between alcohol use, intimate partner violence, and HIV sexual risk behavior among young people in fishing communities from eastern and central Uganda. Therefore, we aimed to determine the association between alcohol use, intimate partner violence, and HIV sexual risk behavior among young people in the fishing communities on the shores of Lake Victoria, in Uganda.

Methods
We conducted multivariable logistic regression analyses of HIV risk behavior using cross-sectional data from 501 young people from Mukono (Katosi landing site) and Namayingo districts (Lugala landing site).

Results
Almost all (97%) respondents reported at least one HIV risk behavior; more than half (54%) reported engagement in three or more HIV risk behaviors. Results from the adjusted model indicate that alcohol use, working for cash or kind, being married, and having multiple sexual partners increased the odds of HIV risk behavior. IPV was not associated with HIV risk behavior.

Conclusion
Interventions to promote consistent condom use and fewer sexual partnerships are critical for young people in the fishing communities in Uganda.
MicroRNA-4429 suppresses proliferation of prostate cancer cells by targeting distal-less homeobox 1 and inactivating the Wnt/β-catenin pathway
Authors: Wang Jinguo , Xie Sheng , Liu Jun , Li Tao , Wang Wanrong , Xie Ziping 
Published: March 2021

Abstract
Background
Emerging evidence suggests that microRNAs (miRNAs) play multiple roles in human cancers through regulating mRNAs and distinct pathways. This paper focused on the functions of miR-4429 in prostate cancer (PCa) progression and the molecules involved.

Methods
Expression of miR-4429 in PCa tissues and cells was determined. Upregulation of miR-4429 was introduced in PCa cells to examine its role in the malignant behaviors of cells. The putative target mRNA of miR-4429 involved in PCa progression was predicted from a bioinformatic system and validated through luciferase assays. Overexpression of distal-less homeobox 1 (DLX1) was further induced in cells to validate its implication in miR-4429-mediated events. The activity of Wnt/β-catenin pathway was determined.

Results
miR-4429 was poorly expressed in PCa tissues and cells. Artificial upregulation of miR-4429 significantly reduced proliferation, growth, invasion, migration and resistance to death of cancer cells and inactivated the Wnt/β-catenin pathway. DLX1 mRNA was found as a target of miR-4429. Upregulation of DLX1 restored the malignant behaviors of PCa cells which were initially suppressed by miR-4429, and it activated the Wnt/β-catenin pathway.

Conclusion
Our study highlights that miR-4429 inhibits the growth of PCa cells by down-regulating DLX1 and inactivating the Wnt/β-catenin pathway. This finding may offer novel insights into PCa treatment.
Evaluation and implementation of a mannequin-based surgical simulator for margin-involving eyelid laceration repair – a pilot study
Authors: Zhao Jiawei , Ahmad Meleha , Gower Emily W. , Fu Roxana , Woreta Fasika A. , Merbs Shannath L. 
Published: March 2021

Abstract
Background
Repair of margin-involving eyelid lacerations is a challenge for beginning ophthalmology residents, yet no commercially-available simulation models exist for learning this skill. The objective of the study was to modify a mannequin-based surgical simulator originally developed for trachomatous trichiasis surgery training to teach margin-involving eyelid laceration repair and to evaluate its success within a residency wet-lab environment.

Methods
We modified a previously developed mannequin-based training system for trachomatous trichiasis surgery into a simulator for margin-involving eyelid laceration repair. Six ophthalmology residents from a tertiary care academic institution performed at least one simulated margin-involving eyelid laceration repair using the surgical simulator between September 2019 and March 2020. Each session was video recorded. Two oculoplastic surgeons reviewed the videos in a blinded fashion to assess surgical proficiency using a standardized grading system. Participants were surveyed on their comfort level with eyelid laceration repair pre- and post-completion of simulation. They were also queried on their perceived usefulness of the surgical simulator compared to past methods and experiences.

Results
Six residents completed 11 simulation surgeries. For three residents who completed more than one session, a slight increase in their skills assessment score and a decrease in operative time over two to three simulation sessions were found. Self-reported comfort level with margin-involving eyelid laceration repairs was significantly higher post-simulation compared to pre-simulation (p = 0.02). Residents ranked the usefulness of our surgical simulator higher than past methods such as fruit peels, surgical skill boards, gloves, and pig feet (p = 0.03) but lower than operating room experience (p = 0.02). Residents perceived the surgical simulator to be as useful as cadaver head and emergency department/consult experience.

Conclusions
We developed a surgical simulator for teaching eyelid laceration repair and showed its utility in developing trainees’ surgical skills. Our surgical simulator was rated to be as useful as a cadaver head but is more readily available and cost effective.
A distinct APC pathogenic germline variant identified in a southern Thai family with familial adenomatous polyposis
Authors: Wanitsuwan Worrawit , Vijasika Sukanya , Jirarattanasopa Pichai , Horpaopan Sukanya 
Published: March 2021

Abstract
Background
Familial adenomatous polyposis (FAP) is caused by pathogenic germline variants in the APC gene. To date, multiple pathogenic variants in coding regions, splice sites, and deep intronic regions have been revealed. However, there are still pathogenic variants that remain unidentified.

Methods
Twenty-nine primer pairs flanking exons 2–16 (i.e., coding exons 1–15) of APC and their exon–intron junctions were used for germline pathogenic variant screening in Southern Thai patients with familial adenomatous polyposis (FAP). Transcription analysis was performed to confirm the pathogenicity of a splice site deletion of intron 10. Family members were interviewed for clinical histories. Blood samples were collected from 18 family members for a segregation study. Subsequently, clinical data of affected members were collected from the hospital databases.

Results
We found a distinct heterozygous 16-bp deletion at the splice donor site of intron 10 leading to a skipping of exon 10 which was confirmed by transcript analysis (APC: c 1312 + 4_1312 + 19del, r.934_1312del). Predictive testing for the pathogenic APC variant in 18 of the proband’s family members (ten healthy and eight affected) from three generations showed the same heterozygous germline pathogenic variant in eight affected adult members (15–62 years old) and two children (7 and 10 years old). Seven of the ten carriers of the disease-causing variant had undergone colonoscopy, and colonic polyps were found in all cases, which confirmed the segregation of the inherited pathogenic variant. The phenotypic spectrum was found to vary within the family; and some affected family members exhibited extracolonic manifestations.

Conclusions
To our knowledge, the pathogenic APC variant, c.1312 + 4_1312 + 19del, r.934_1312del, has not previously been reported. This study is one of the few reports describing the phenotypic consequences of a pathogenic APC variant in a high number of affected family members.
Assessing the quality of information provided on websites selling Kratom (Mitragyna speciosa) to consumers in Canada
Authors: Ng Jeremy Y. , Ans Muhammad , Marwaha Amn 
Published: March 2021

Abstract
Background
Amid a Canadian opioid crisis, many have turned to natural health products, such as kratom (Mitragyna speciosa), to manage their opioid withdrawal. Kratom has also been reported to relieve anxiety, improve stamina, and heighten physical performance. Given that kratom is not authorized for sale by Health Canada, many have turned to online retailers to purchase kratom due to its easy accessibility online. This study investigated the quality of consumer health information provided on the websites of online vendors selling kratom to consumers in Canada.

Methods
Following searches on Google.ca using search terms designed to simulate the information-seeking behaviour of a typical patient-user online, eligible websites were assessed using the 16-question DISCERN instrument, a tool designed to assess the quality of consumer health information. Searches were conducted on March 27, 2020 and only websites presenting information in English were included.

Results
A total of 200 webpages were identified; after screening based on eligibility criteria and combining different webpages that belonged to the same website, 51 websites were found to be eligible. The mean summed DISCERN score across all 51 websites was 36.95 (SD = 2.44) out of 75, which reflects poor quality consumer health information across the subset of websites. The overall quality of websites was poor, as 78% (n = 40) of vendors received a score of 2 or less out of 5.

Conclusions
Individuals who seek information about kratom online are frequently exposed to poor quality consumer health information. Those looking to purchase kratom online are not provided with the critical information necessary to make an informed decision regarding its use, such as the complete details about the risks and side effects or a description of how kratom affects the body. Given the growing interest in kratom, knowledge of the quality of information available can lead to improved dialogue between healthcare providers and patients.
The effect of the platelet-rich plasma and ozone therapy on tendon-to-bone healing in the rabbit rotator cuff repair model
Authors: Gurger Murat , Once Gokhan , Yilmaz Erhan , Demir Sukru , Calik Ilknur , Say Yakup , Kavakli Ahmet , Key Sefa , Gurbuz Mustafa Umit , Bingollu Onur 
Published: March 2021

AbstractBackgroundThe aim of this study is to histologically and biomechanically investigate the effects of local PRP and ozone therapy (O2O3) on tendon-to-bone healing in a rabbit model of the supraspinatus tendon tear.MethodsFour groups were formed to have seven rabbits in each group: repair, R; repair + PRP, RP; repair + ozone, RO; and repair + PRP + ozone, RPO. The supraspinatus tendon was detached by sharp dissection from the footprint and an acute tear pattern was created. Thereafter, tendon repair was performed with the transosseous technique. In the RP group, PRP, and in the RPO group, PRP + O2O3 mixture was injected to the tendon repair site. In the RO group, O2O3gas mixture was injected into subacromial space three times a week for a total of 4 weeks. The study was ended at postoperative 6th week.ResultsWhen compared with the R group, a statistically significant increase was observed in the biomechanical strength of the RP and RPO groups. The highest increase in biomechanical strength was detected in the RPO group. The histology of the RO and RPO groups showed better collagen fiber continuity and orientation than the R and RP groups.ConclusionsThe results obtained from this study show that the ozonized PRP can be used as biological support to increase tendon-to-bone healing. However, these results need to be supported by clinical studies.
Hip pathologies in mucopolysaccharidosis type III
Authors: Breyer Sandra Rafaela , Vettorazzi Eik , Schmitz Leonie , Gulati Amit , von Cossel Katharina Maria , Spiro Alexander , Rupprecht Martin , Stuecker Ralf , Muschol Nicole Maria 
Published: March 2021

Abstract
Background
Mucopolysaccharidosis type III (MPS III) comprises a group of rare lysosomal storage diseases. Although musculoskeletal symptoms are less pronounced than in other MPS subtypes, pathologies of hip and spine have been reported in MPS III patients. The purpose of this study was to describe hip pathologies and influencing parameters in MPS III patients.

Methods
A retrospective chart review was performed for 101 MPS III patients. Thirty-two patients met the inclusion criteria of enzymatically or genetically confirmed diagnosis and anteroposterior radiograph of the hips. Modified Ficat classification, Wiberg’s center-edge angle, and Reimer’s migration percentage were measured.

Results
The mean age at data assessment was 11.0 years (SD 5.7). Osteonecrosis of the femoral head was observed in 17/32 patients. No statistically significant association was found between these changes and age, sex, or MPS III subtype. Patients with a severe phenotype showed significantly higher rates of osteonecrosis (14/17) than patients with an intermediate phenotype. Hip dysplasia was present in 9/32 patients and was significantly associated with osteonecrosis of the femoral head (p = 0.04).

Conclusions
The present study demonstrates a high rate of hip pathologies in MPS III patients. Hip dysplasia and severe phenotype were significantly correlated with osteonecrosis of the femoral head. Therefore, radiographs of the hips are highly recommended in baseline and follow-up assessments of MPS III patients.

Trial registration
Retrospectively registered.
Aqueous extracts of Aconite promote thermogenesis in rats with hypothermia via regulating gut microbiota and bile acid metabolism
Authors: Liu Juan , Tan Yuzhu , Ao Hui , Feng Wuwen , Peng Cheng 
Published: March 2021

Abstract
Background
Intermittent or prolonged exposure to severe cold stress disturbs energy homeostasis and can lead to hypothermia, heart failure, Alzheimer’s disease, and so on. As the typical “hot” traditional Chinese medicine, Aconite has been widely used to treat cold-associated diseases for thousands of years, but its critical mechanisms for the promotion of thermogenesis are not fully resolved. Gut microbiota and its metabolites play a crucial role in maintaining energy homeostasis. Here, we investigated whether the aqueous extracts of Aconite (AA) can enhance thermogenesis through modulation of the composition and metabolism of gut microbiota in hypothermic rats.

Methods
The therapeutic effects of AA on body temperature, energy intake, and the histopathology of white adipose tissue and brown adipose tissue of hypothermic rats were assessed. Microbiota analysis based on 16 S rRNA and targeted metabolomics for bile acids (BAs) were used to evaluate the composition of gut microbiota and BAs pool. The antibiotic cocktail treatment was adopted to further confirm the relationship between the gut microbiota and the thermogenesis-promoting effects of AA.

Results
Our results showed a sharp drop in rectal temperature and body surface temperature in hypothermic rats. Administration of AA can significantly increase core body temperature, surface body temperature, energy intake, browning of white adipose tissue, and thermogenesis of brown adipose tissue. Importantly, these ameliorative effects of AA were accompanied by the shift of the disturbed composition of gut microbiota toward a healthier profile and the increased levels of BAs. In addition, the depletion of gut microbiota and the reduction of BAs caused by antibiotic cocktails reduced the thermogenesis-promoting effect of AA.

Conclusions
Our results demonstrated that AA promoted thermogenesis in rats with hypothermia via regulating gut microbiota and BAs metabolism. Our findings can also provide a novel solution for the treatment of thermogenesis-associated diseases such as rheumatoid arthritis, obesity, and type 2 diabetes.
Preclinical modeling of chronic inhibition of the Parkinson’s disease associated kinase LRRK2 reveals altered function of the endolysosomal system in vivo
Authors: Kluss Jillian H. , Mazza Melissa Conti , Li Yan , Manzoni Claudia , Lewis Patrick A. , Cookson Mark R. , Mamais Adamantios 
Published: March 2021

AbstractThe most common mutation in the Leucine-rich repeat kinase 2 gene (LRRK2), G2019S, causes familial Parkinson’s Disease (PD) and renders the encoded protein kinase hyperactive. While targeting LRRK2 activity is currently being tested in clinical trials as a therapeutic avenue for PD, to date, the molecular effects of chronic LRRK2 inhibition have not yet been examined in vivo. We evaluated the utility of newly available phospho-antibodies for Rab substrates and LRRK2 autophosphorylation to examine the pharmacodynamic response to treatment with the potent and specific LRRK2 inhibitor, MLi-2, in brain and peripheral tissue in G2019S LRRK2 knock-in mice. We report higher sensitivity of LRRK2 autophosphorylation to MLi-2 treatment and slower recovery in washout conditions compared to Rab GTPases phosphorylation, and we identify pS106 Rab12 as a robust readout of downstream LRRK2 activity across tissues. The downstream effects of long-term chronic LRRK2 inhibition in vivo were evaluated in G2019S LRRK2 knock-in mice by phospho- and total proteomic analyses following an in-diet administration of MLi-2 for 10 weeks. We observed significant alterations in endolysosomal and trafficking pathways in the kidney that were sensitive to MLi-2 treatment and were validated biochemically. Furthermore, a subtle but distinct biochemical signature affecting mitochondrial proteins was observed in brain tissue in the same animals that, again, was reverted by kinase inhibition. Proteomic analysis in the lung did not detect any major pathway of dysregulation that would be indicative of pulmonary impairment. This is the first study to examine the molecular underpinnings of chronic LRRK2 inhibition in a preclinical in vivo PD model and highlights cellular processes that may be influenced by therapeutic strategies aimed at restoring LRRK2 physiological activity in PD patients.
Exosomal miR-106b-5p derived from melanoma cell promotes primary melanocytes epithelial-mesenchymal transition through targeting EphA4
Authors: Luan Wenkang , Ding Yuting , Xi Haolan , Ruan Hongru , Lu Feng , Ma Shaojun , Wang Jinlong 
Published: March 2021

Abstract
Background
Cancer-secreted exosomal miRNAs regulates the biological processes of many tumours. The serum level of exosomal miR-106b-5p is significantly increased in melanoma patients. However, the role and molecular mechanisms of exosomal miR-106b-5p in melanoma remains unclear.

Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-106b-5p and EphA4 in melanoma tissues. Transmission electron microscopy (TEM) and western blotting were used to identify exosome. QRT-qPCR and Cy3-labelled miR-106b-5p were used to demonstrated the transmission of melanoma cell-secreted exosomal miR-106b-5p. Western blotting, Immunofluorescence, adhesion, transwell and scratch wound assay were used to explore the role of exosomal miR-106b-5p in melanocytes. Luciferase reporter assays and RNA-Chromatin Immunoprecipitation (ChIP) assay were used to confirm whether erythropoietin-producing hepatocellular carcinoma receptor A4 (EphA4) was a direct target of miR-106b-5p.

Results
We found that miR-106b-5p levels were increased in melanoma tissue, and high miR-106b-5p expression is an independent risk factor for the overall survival of patients with melanoma. miR-106b-5p is enriched in melanoma cell-secreted exosomes and transferred to melanocytes. Exosomal miR-106b-5p promotes the epithelial-to-mesenchymal transition (EMT), migration, invasion and adhesion of melanocytes. Exosomal miR-106b-5p exerted its role by targeting EphA4 to activate the ERK pathway. We demonstrated that exosomal miR-106b-5p promoted melanoma metastasis in vivo through pulmonary metastasis assay.

Conclusions
Thus, melanoma cell-secreted exosomal miR-106b-5p may serve as a diagnostic indicator and potential therapeutic target in melanoma patients.
Early effects of ventilatory rescue therapies on systemic and cerebral oxygenation in mechanically ventilated COVID-19 patients with acute respiratory distress syndrome: a prospective observational study
Authors:   collaborators, Robba Chiara , Ball Lorenzo , Battaglini Denise , Cardim Danilo , Moncalvo Emanuela , Brunetti Iole , Bassetti Matteo , Giacobbe Daniele R. , Vena Antonio , Patroniti Nicolò , Rocco Patricia R. M. , Matta Basil F. , Pelosi Paolo 
Published: March 2021

AbstractBackgroundIn COVID-19 patients with acute respiratory distress syndrome (ARDS), the effectiveness of ventilatory rescue strategies remains uncertain, with controversial efficacy on systemic oxygenation and no data available regarding cerebral oxygenation and hemodynamics.MethodsThis is a prospective observational study conducted at San Martino Policlinico Hospital, Genoa, Italy. We included adult COVID-19 patients who underwent at least one of the following rescue therapies: recruitment maneuvers (RMs), prone positioning (PP), inhaled nitric oxide (iNO), and extracorporeal carbon dioxide (CO2) removal (ECCO2R). Arterial blood gas values (oxygen saturation [SpO2], partial pressure of oxygen [PaO2] and of carbon dioxide [PaCO2]) and cerebral oxygenation (rSO2) were analyzed before (T0) and after (T1) the use of any of the aforementioned rescue therapies. The primary aim was to assess the early effects of different ventilatory rescue therapies on systemic and cerebral oxygenation. The secondary aim was to evaluate the correlation between systemic and cerebral oxygenation in COVID-19 patients.ResultsForty-five rescue therapies were performed in 22 patients. The median [interquartile range] age of the population was 62 [57–69] years, and 18/22 [82%] were male. After RMs, no significant changes were observed in systemic PaO2and PaCO2values, but cerebral oxygenation decreased significantly (52 [51–54]% vs. 49 [47–50]%,p < 0.001). After PP, a significant increase was observed in PaO2(from 62 [56–71] to 82 [76–87] mmHg,p = 0.005) and rSO2(from 53 [52–54]% to 60 [59–64]%,p = 0.005). The use of iNO increased PaO2(from 65 [67–73] to 72 [67–73] mmHg,p = 0.015) and rSO2(from 53 [51–56]% to 57 [55–59]%,p = 0.007). The use of ECCO2R decreased PaO2(from 75 [75–79] to 64 [60–70] mmHg,p = 0.009), with reduction of rSO2values (59 [56–65]% vs. 56 [53–62]%,p = 0.002). In the whole population, a significant relationship was found between SpO2and rSO2(R = 0.62,p < 0.001) and between PaO2and rSO2(R0 0.54,p < 0.001).ConclusionsRescue therapies exert specific pathophysiological mechanisms, resulting in different effects on systemic and cerebral oxygenation in critically ill COVID-19 patients with ARDS. Cerebral and systemic oxygenation are correlated. The choice of rescue strategy to be adopted should take into account both lung and brain needs.RegistrationThe study protocol was approved by the ethics review board (Comitato Etico Regione Liguria, protocol n. CER Liguria: 23/2020).