bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of potential DNA methylation biomarkers related to diagnosis in patients with bladder cancer through integrated bioinformatic analysis
Authors: Cheng Hongxia , Liu Yuhua , Chen Gang
Published: August 2023

Background

Bladder cancer (BLCA) is one of the most common malignancies among tumors worldwide. There are no validated biomarkers to facilitate such treatment diagnosis. DNA methylation modification plays important roles in epigenetics. Identifying methylated differentially expressed genes is a common method for the discovery of biomarkers.

Methods

Bladder cancer data were obtained from Gene Expression Omnibus (GEO), including the gene expression microarrays GSE37817( 18 patients and 3 normal ), GSE52519 (9 patients and 3 normal) and the gene methylation microarray GSE37816 (18 patients and 3 normal). Aberrantly expressed genes were obtained by GEO2R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed using the DAVID database and KOBAS. Protein-protein interactions (PPIs) and hub gene networks were constructed by STRING and Cytoscape software. The validation of the results which was confirmed through four online platforms, including Gene Expression Profiling Interactive Analysis (GEPIA), Gene Set Cancer Analysis (GSCA), cBioProtal and MEXPRESS.

Results

In total, 253 and 298 upregulated genes and 674 and 454 downregulated genes were identified for GSE37817 and GSE52519, respectively. For the GSE37816 dataset, hypermethylated and hypomethylated genes involving 778 and 3420 genes, respectively, were observed. Seventeen hypermethylated and low expression genes were enriched in biological processes associated with different organ development and morphogenesis. For molecular function, these genes showed enrichment in extracellular matrix structural constituents. Pathway enrichment showed drug metabolic enzymes and several amino acids metabolism, PI3K-Akt, Hedgehog signaling pathway. The top 3 hub genes screened by Cytoscape software were EFEMP1, SPARCL1 and ABCA8. The research results were verified using the GEPIA, GSCA, cBioProtal and EXPRESS databases, and the hub hypermethylated low expression genes were validated.

Conclusion

This study screened possible aberrantly methylated expression hub genes in BLCA by integrated bioinformatics analysis. The results may provide possible methylation-based biomarkers for the precise diagnosis and treatment of BLCA in the future.
SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 gene predict dosage requirements in a cross-sectional sample of hypothyroid patients
Authors: AlEjielat Rowan , Khaleel Anas , Batarseh Yazan S. , Abu-Qatouseh Luay , Al-Wawi Suzan , AlSunna Toleen
Published: August 2023

Background and purpose

Primary hypothyroidism due to abnormality in the thyroid gland is the most common endocrine disease The recommended starting dose of levothyroxine replacement therapy is 1.6 µg/kg. This dose however is not optimal for every patient and dose adjustments are frequently done. Genetic polymorphisms in the absorption and metabolism pathway of levothyroxine are likely to influence its dose requirements. This study aimed to study the influence of genetic polymorphisms on levothyroxine replacement requirements.

Methods

This was a cross-sectional study. Participants were recruited through a private nutrition clinic and through announcements distributed in the University of Petra in Amman, Jordan between September 2020 and February 2021. Hypothyroid patients had already been on stable doses of levothyroxine for the previous 3 months. A questionnaire was distributed to collect demographic and clinical information and a blood sample was taken for DNA extraction and clinical biochemistry analysis. rs11249460, rs2235544, rs225014, rs225015, rs3806596, rs11185644, rs4588, rs602662 were analyzed using Applied Biosystems TaqMan™ SNP Genotyping Assays on Rotor-Gene® Q and rs3064744 by direct sequencing. SPSS and Excel were used to perform analysis.

Results

76 patients were studied. The equation we calculated to find predicted daily dose of levothyroxine (mcg/kg) is 3.22+ (0.348 for CT genotype of rs11185644, 0 for other genotypes) + 0.027*disease duration (years) − 0.014*age (years) − 0.434*T3 (pmol/L) levels+ (0.296 for CC genotype of rs2235544, 0 for other genotypes).

Conclusion

SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 affect dose requirement in hypothyroid patients and if confirmed in larger trials they can be used to individualize thyroxine starting doses.
Exploring the safety and efficacy of phytomedicine Petiveria alliacea extract (Esperanza) in patients with metastatic gastrointestinal tumors and acute leukemias: study protocol for a phase Ib/randomized double blind phase II trial (PA001)
Authors: Ballesteros-Ramírez Ricardo , Pinilla Paola , Sanchéz Jesús , Arévalo Mónica , Sanchez Elio , Aschner Pablo , Urueña Claudia , Fiorentino Susana
Published: August 2023

Background

The energy metabolism of drug-resistant tumor cells can provide a survival advantage during therapy, and treatment itself may influence metabolic reprogramming. Petiveria alliacea (Traditional name: Anamu) could inhibit glycolysis and OXPHOX modulating tumor metabolism, making it a potential treatment for tumors with altered metabolism. This clinical study aims to evaluate the safety and efficacy of a standardized Anamu phytomedicine called Esperanza in treating gastric tumors and acute leukemias.

Methods

This is a prospective, open label, phase I/ randomized, double-blind single-center phase II study designed to evaluate the safety and efficacy of Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias. In stage 1, the study will determine the MTD and assess safety. In stage 2, safety at the MTD will be evaluated, and the efficacy of Esperanza extract will be explored in both metastatic gastric tumors and acute leukemias. Quality of life improvement will be the primary outcome in the gastric tumor group, while different efficacy outcomes will be assessed in the acute leukemia group. A placebo group will be used for comparison in the gastric tumor group, and a historical control group will be used in the acute leukemia arm.

Discussion

This clinical trial aims to evaluate the safety profile of the Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias, while exploring its potential efficacy in conjunction with standard treatment for these pathologies.

Trial registration

This trial was registered in the US National Library of Medicine with identifier NCT05587088. Registered October 19th, 2022.
Development of a conceptual model of the capacity for patients to engage in their health care: a group concept mapping study
Authors: Di Tosto Gennaro , Hefner Jennifer L. , Walker Daniel M. , Gregory Megan E. , McAlearney Ann Scheck , Sieck Cynthia J.
Published: August 2023

Background

Patient engagement is seen as a necessary component in achieving the triple aim of improved population health, improved experience of care, and lower per capita health care costs. While there has been a substantial increase in the number of tools and patient-centered initiatives designed to help patients participate in health decisions, there remains a limited understanding of engagement from the perspective of patients and a lack of measures designed to capture the multi-faceted nature of the concept.

Methods

Development of a concept map of patient engagement followed a five-step modified Group Concept Mapping (GCM) methodology of preparation, generation, structuring, analysis and interpretation. We engaged a Project Advisory Committee at each step, along with three rounds of survey collection from clinicians and patients for element generation (272 clinicians, 61 patients), statement sorting (30 clinicians, 15 patients), and ranking and rating of statements (159 clinicians, 67 patients). The survey of three separate samples, as opposed to focus groups of ‘experts,’ was an intentional decision to gain a broad perspective about the concept of patient engagement. We conducted the structure and analysis steps within the groupwisdom concept mapping software.

Results

The final concept map comprised 47 elements organized into 5 clusters: Relationship with Provider, Patient Attitudes and Behaviors, Access, Internal Resources and External Resources. There was considerable agreement in the way elements in each cluster were rated by patients and clinicians. An analysis of the importance of the constitutive elements of patient engagement relative to their addressability highlighted actionable items in the domain of Relationship with Provider, aimed at building trust and enabling patients to ask questions. At the same time, the analysis also identified elements traditionally considered barriers to engagement, like personal access to the internet and the patient’s level of digital literacy, as difficult to address by the healthcare system, but also relatively less important for patients.

Conclusions

Through our GCM approach, incorporating perspectives of both patients and clinicians, we identified items that can be used to assess patient engagement efforts by healthcare systems. As a result, our study offers specific insight into areas that can be targeted for intervention by healthcare systems to improve patient engagement.
National digital strategies and innovative eHealth policies concerning older adults’ dignity: a document analysis in three Scandinavian countries
Authors: Raja Moonika , Kymre Ingjerd G. , Bjerkan Jorunn , Galvin Kathleen T. , Uhrenfeldt Lisbeth
Published: August 2023

Background

Scandinavian countries are internationally recognised for leading the way in older adult care and in digitally transforming healthcare. Dignity has become a central value in care for older adults in all three Scandinavian countries. Investigating documents about digitalisation in these countries can offer insights into how the dignity of older adults is impacted by digitally transforming healthcare. This study aims to provide knowledge about digital strategies and eHealth policies concerning older adults’ dignity in three Scandinavian countries: Norway, Sweden and Denmark.

Methods

National-level documents by the Norwegian Directorate of eHealth, the Norwegian Directorate of Health, the Swedish Ministry of Health and Social Affairs and the Danish Ministry of Health concerning older adults were used as data sources. In addition, a systematic search of databases, informed by the Joanna Briggs Institute framework for systematic reviews of text and opinion papers, was undertaken to find relevant papers. All extracts concerning national digital strategies or innovative eHealth policies were deductively coded. Thereafter, extracts concerning older adults were inductively coded using a thematic analytic approach.

Results

A total of 26 sources satisfied the inclusion criteria, 14 governmental papers and 12 other papers. The three countries’ national digital strategies focused on access to digital technologies and continuous learning for digital skills. The included papers describing national eHealth policies underlined the importance of placing the patient at the centre of healthcare and how digital systems can increase feelings of safety. Both types of documents concerned access to data, digital device security and the human dimension of care.

Conclusion

The findings present evidence on Scandinavian countries’ national digital strategies and innovative eHealth policies concerning older adults’ dignity. The documents describe a lack of digital competence among older adults, resulting disengagement may put their well-being and human dignity at risk. Findings also underline the importance of security and at the same time the human dimension of care: Use of new digital systems must be meaningfully integrated into digital strategies and eHealth policies. All three Scandinavian countries strategies and policies underline the importance of equal access to healthcare services, as thus they promote a stance of dignified care.
Detection of polymyxins resistance among Enterobacterales: evaluation of available methods and proposal of a new rapid and feasible methodology
Authors: Collar Gabriela da Silva , Moreira Natália Kehl , Wink Priscila Lamb , Barth Afonso Luís , Raro Otávio Hallal Ferreira , Dias Cícero , de Lima Machado Adriano , Mott Mariana Preussler , Caierão Juliana
Published: August 2023

Background

Fast and accurate detection of polymyxins resistance is necessary as they remain the last resources to treat infections caused by Carbapenem-resistant Enterobacterales in many regions. We evaluated the rapid colorimetric polymyxin B elution (RCPE) and developed its miniaturized version, RCPE microelution (RCPEm), aiming to detect polymyxins resistance among Enterobacterales.

Methods

The methodologies consist of exposing the bacterial population in a solution (NP solution) where polymyxin B disks were previously eluted to obtain a concentration of 2 µg/mL for RCPE and 3 µg/mL for RCPEm.

Results

Two hundred sixty-seven Enterobacterales were evaluated, 90 (33.7%) resistant to polymyxin B by broth microdilution. It was observed 0.6% of major error (ME) by RCPE, with a specificity of 99.4%. The miniaturized version (RCPEm) presented the same ME and specificity values, but slightly higher sensitivity (97.8% vs. 95.6%) with 2.2% of very major error (VME).

Conclusions

RCPE and RCPEm proved to be useful alternatives to determine polymyxin B susceptibility in clinical microbiology laboratories, presenting low cost, being easy to perform, and demanding short incubation time.
Association between nineteen dietary fatty acids and hearing thresholds: findings from a nationwide survey
Authors: Zhang Xiaojin , Luo Qin , Huang Zhicheng , Xiang Xin
Published: August 2023

Introduction

Hearing loss is a prevalent health concern, and dietary factors, such as fatty acid intake, may play a role in its development. The current study aimed to investigate the association between the intake of dietary fatty acids and hearing thresholds among U.S. adults.

Methods

The researchers examined data from the National Health and Nutrition Examination Survey (NHANES), including 7,623 participants with available dietary fatty acid intake and audiometry data. Dietary fatty acid intake was assessed using dietary recalls, and hearing thresholds were measured using pure-tone audiometry. Multivariate linear regression models and smoothing curve fitting were utilized to explore the associations between dietary fatty acid intake and hearing thresholds, adjusting for relevant covariates.

Results

This study reveals a direct association between both low and high frequency pure tone average (PTA) hearing thresholds and the dietary intake of total saturated fatty acids (SFAs) and total polyunsaturated fatty acids (PUFAs). Conversely, the intake of total monounsaturated fatty acids (MUFAs) demonstrates an inverted U-shaped correlation with low-frequency and high-frequency PTA hearing thresholds, having inflection points at 11.91 (energy (%)) and 10.88 (energy (%)), respectively.

Conclusion

Dietary intake of certain fatty acids may influence hearing thresholds in adults.
Iron-based metal-organic framework co-loaded with buthionine sulfoximine and oxaliplatin for enhanced cancer chemo-ferrotherapy via sustainable glutathione elimination
Authors: Rao Zhiping , Xia Yutian , Jia Qian , Zhu Yutong , Wang Lexuan , Liu Guohuan , Liu Xuelan , Yang Peng , Ning Pengbo , Zhang Ruili , Zhang Xianghan , Qiao Chaoqiang , Wang Zhongliang
Published: August 2023

Background

Emerging ferroptosis-driven therapies based on nanotechnology function either by increasing intracellular iron level or suppressing glutathione peroxidase 4 (GPX4) activity. Nevertheless, the therapeutic strategy of simultaneous iron delivery and GPX4 inhibition remains challenging and has significant scope for improvement. Moreover, current nanomedicine studies mainly use disulfide-thiol exchange to deplete glutathione (GSH) for GPX4 inactivation, which is unsatisfactory because of the compensatory effect of continuous GSH synthesis.

Methods

In this study, we design a two-in-one ferroptosis-inducing nanoplatform using iron-based metal-organic framework (MOF) that combines iron supply and GPX4 deactivation by loading the small molecule buthionine sulfoxide amine (BSO) to block de novo GSH biosynthesis, which can achieve sustainable GSH elimination and dual ferroptosis amplification. A coated lipid bilayer (L) can increase the stability of the nanoparticles and a modified tumor-homing peptide comprising arginine-glycine-aspartic acid (RGD/R) can achieve tumor-specific therapies. Moreover, as a decrease in GSH can alleviate resistance of cancer cells to chemotherapy drugs, oxaliplatin (OXA) was also loaded to obtain BSO&OXA@MOF-LR for enhanced cancer chemo-ferrotherapy in vivo.

Results

BSO&OXA@MOF-LR shows a robust tumor suppression effect and significantly improved the survival rate in 4T1 tumor xenograft mice, indicating a combined effect of dual amplified ferroptosis and GSH elimination sensitized apoptosis.

Conclusion

BSO&OXA@MOF-LR is proven to be an efficient ferroptosis/apoptosis hybrid anti-cancer agent. This study is of great significance for the clinical development of novel drugs based on ferroptosis and apoptosis for enhanced cancer chemo-ferrotherapy.

Graphical Abstract
ZIF-8 induced hydroxyapatite-like crystals enabled superior osteogenic ability of MEW printing PCL scaffolds
Authors: Wang Bingqian , Zeng Yuyang , Liu Shaokai , Zhou Muran , Fang Huimin , Wang Zhenxing , Sun Jiaming
Published: August 2023

ZIF-8 may experience ion-responsive degradation in ionic solutions, which will change its initial architecture and restrict its direct biological use. Herein, we report an abnormal phenomenon in which ZIF-8 induces large hydroxyapatite-like crystals when soaked directly in simulated body fluid. These crystals grew rapidly continuously for two weeks, with the volume increasing by over 10 folds. According to Zn2+ release and novel XRD diffraction peak presence, ZIF-8 particles can probably show gradual collapse and became congregate through re-nucleation and competitive coordination. The phenomenon could be found on ZIF-8/PCL composite surface and printed ZIF-8/PCL scaffold surface. ZIF-8 enhanced PCL roughness through changing the surface topography, while obviously improving the in-vivo and in-vitro osteoinductivity and biocompatibility. The pro-biomineralization property can make ZIF-8 also applicable in polylactic acid-based biomaterials. In summary, this study demonstrates that ZIF-8 may play the role of a bioactive additive enabling the surface modification of synthetic polymers, indicating that it can be applied in in-situ bone regeneration.
Facile and eco-friendly fabrication of biocompatible hydrogel containing CuS@Ser NPs with mechanical flexibility and photothermal antibacterial activity to promote infected wound healing
Authors: Guo Ye , Xie Bingqing , Jiang Min , Yuan Lingling , Jiang Xueyu , Li Silei , Cai Rui , Chen Junliang , Jiang Xia , He Yun , Tao Gang
Published: August 2023

Bacterial infections can significantly impede wound healing and pose a serious threat to the patient’s life. The excessive use of antibiotics to combat bacterial infections has led to the emergence of multi-drug-resistant bacteria. Therefore, there is a pressing need for alternative approaches, such as photothermal therapy (PTT), to address this issue. In this study, for the first time, CuS NPs with photothermal properties were synthesized using sericin as a biological template, named CuS@Ser NPs. This method is simple, green, and does not produce toxic and harmful by-products. These nanoparticles were incorporated into a mixture (XK) of xanthan gum and konjac glucomannan (KGM) to obtain XK/CuS NPs composite hydrogel, which could overcome the limitations of current wound dressings. The composite hydrogel exhibited excellent mechanical flexibility, photothermal response, and biocompatibility. It also demonstrated potent antibacterial properties against both Gram-positive and negative bacteria via antibacterial experiments and accelerated wound healing in animal models. Additionally, it is proved that the hydrogel promoted tissue regeneration by stimulating collagen deposition, angiogenesis, and reducing inflammation. In summary, the XK/CuS NPs composite hydrogel presents a promising alternative for the clinical management of infected wounds, offering a new approach to promote infected wound healing.
Estimating health related quality of life effects in vitiligo. Mapping EQ-5D-5 L utilities from vitiligo specific scales: VNS, VitiQoL and re-pigmentation measures using data from the HI-Light trial
Authors: Begum Rabiah , Crott Ralph , Martina Reynaldo , Loizidou Eleni M. , Khan Iftekhar
Published: August 2023

Background

Vitiligo is reported to affect 2% of the world’s population and has a significant impact on health related quality of life (HRQoL). The relationship between HRQoL and clinical outcomes used in vitiligo require further examination. Mapping condition specific measures of HRQoL: vitiligo specific quality of life instrument (VitiQoL), vitiligo noticeability scale (VNS) and vitiligo re-pigmentation scores (RPS) to the EQ-5D have not yet been reported.

Methods

Data collected from a randomised clinical trial (HI-Light) in vitiligo was used to develop mapping algorithms for the EQ-5D-5 L and the relationship between HRQoL, clinical outcomes and EQ-5D were investigated. Two EQ-5D-5 L value sets (Van Hout and Alava) using linear and non-linear models were considered. Logistic regression models were used to model the probability of vitiligo noticeability (VNS) in terms of RPS, EQ-5D and VitiQoL scores.

Results

Mapping from RPS appeared to perform better followed by VNS for the Alava crosswalks using polynomial models: Mean observed vs. predicted utilities of 0.9008 (0.005) vs. 0.8984 (0.0004) were observed for RPS. For VNS, mean observed vs. predicted utilities of 0.9008 (0.005) vs. 0.8939 (0.0003) were observed. For VitiQoL, mean observed vs. predicted utilities of 0.9008 (0.005) vs. 0.8912 (0.0002) were observed. For patients with the least re-pigmentation (RPS < 25%), a Total VitiQoL score of about 20 points gives around an 18% chance of vitiligo being no longer or a lot less noticeable.

Conclusion

The algorithm based on RPS followed by VNS performed best. The relationship between effects from vitiligo specific HRQoL instruments and clinical RPS was established allowing for plausible clinically relevant differences to be identified, although further work is required in this area.
Evidence-based maintenance care among chiropractors in Norway: a cross-sectional survey in the Nordic maintenance care program
Authors: Myhrvold Birgitte Lawaetz , Vikhaug Tora Bjørkmann , DuRose Alister , Gausel Anne Marie , Eklund Andreas , Axén Iben
Published: August 2023

Background

Chiropractors use a treatment strategy called maintenance care with the intent of secondary and tertiary prevention. The Nordic Maintenance Care Program provides evidence of when and for whom maintenance care should be offered. Dissemination has occurred through articles, workshops, social media, conference in Europe and internationally. However, little is known about chiropractors’ awareness and use of this evidence. This study explores chiropractors’ attitudes, skills, and use of evidence on maintenance care, as well as study their association with general evidence-based practice and demographic characteristics. Moreover, barriers and facilitators of evidence access are also examined.

Methods

Questions pertaining our research aim were included in the anonymous and digital Evidence-Based practice Attitude and utilization SurvEy, which was distributed to all members (n = 770) of the Norwegian chiropractic association in the fall of 2021.

Results

The response rate was 41% (n = 312). Regarding attitudes towards evidence-based maintenance care, 26% agreed they needed tools to recommend this care to patients. Approximately half (57%) believed they had skills to identify suitable patients, and 45% had used published information in the past month. Strong alignment was observed between Norwegian chiropractors’ attitudes, skills, and utilization of evidence-based maintenance care and general evidence-based practice. Maintenance care skills were significantly associated with age (those between 40 and 59 years being less likely to report having high skills), clinical setting (those working with conventional health care providers being less likely to report having high skills) and country of education (those educated in the US and Australia being more likely to report having high skills). Moreover, maintenance care use was significantly associated with country of education (those educated in Australia were less likely to have used published information regarding patient selection for maintenance care). Access to resources was a barrier, whereas knowledge of patient suitability facilitated evidence-based maintenance care.

Conclusions

Norwegian chiropractors had neutral attitudes towards maintenance care, but generally reported moderate skills. Most had not used evidence about maintenance care in the previous month. Access to useful resources about the evidence regarding maintenance care was a barrier, and knowledge of who responds to maintenance care was a facilitator.
Teaching antenatal hand expression: a feasibility study in an inner urban U.S. hospital
Authors: Chen Sally , Washio Yukiko , Liu Angela , Acker Colette , Herrine Gail
Published: August 2023

Background

Many women have low confidence in breastfeeding and have concerns regarding low milk volume or discomfort with breastfeeding. Antenatal hand expression may be an opportunity to help women feel more comfortable with breastfeeding and help promote exclusive breastfeeding. A study at a hospital in Philadelphia, Pennsylvania, U.S. assessed the feasibility of teaching antenatal hand expression at 39 weeks among socioeconomically disadvantaged populations, overall participant satisfaction and adoption of hand expression and breastfeeding.

Methods

From March 2020 to June 2021, women recruited at 34–39 weeks were taught to hand express, collect, and store colostrum. Starting from 39 weeks, participants were asked to practice hand expression 1–3 times / day until delivery, log their experiences, and store colostrum expressed. Women were contacted to encourage continued hand expression and answer any questions. Postpartum, a survey assessed satisfaction with hand expression and issues encountered. The survey also inquired about breastfeeding plans and barriers, and whether women were exclusively breastfeeding (defined as infants who received only breastmilk from the time of birth). Chart review of postpartum or well-baby visit notes determined whether women continued breastfeeding.

Results

Of the 29 participants, 72% (21/29) reported hand expressing at home, and no women reported contractions when hand expressing. Participants rated mean satisfaction of 8.1/10 (SD = 1.62) with antenatal hand expression, mean satisfaction of 9.4/10 (SD = 0.90) toward hand expression education, mean likelihood of 9.4/10 (SD = 1.24) recommending hand expression to others, and a mean score of 8.1/10 (SD = 1.69) on how helpful hand expression was in breastfeeding initiation. 90% (26/29) of women initiated breastfeeding after birth and 72% (21/29) exclusively breastfed on discharge, but only 11/29 (38%) continued exclusively breastfeeding when re-assessed 4–6 weeks postpartum. Barriers included maternal discomfort, low milk supply, and maternal or infant illness.

Conclusions

This study suggests that women in an urban setting would be willing to practice antenatal hand expression. A larger and adequately powered study could be feasible to determine associations between antenatal hand expression and breastfeeding rates and confidence.
Topical streptomycin irrigation of lesions to prevent postoperative site infections in spinal tuberculosis: a retrospective analysis
Authors: Du Jianqiang , Qin Wenxiu , Zhang Yanjun , Yang Zhengyuan , Li Junjie , Yang Jun , Deng Qiang
Published: August 2023

Purpose

In spinal tuberculosis surgery, topical administration of drugs to the lesion is a preventive treatment measure. The aim is to achieve better bacterial inhibition and to prevent complications. As one of the most common complications after spinal tuberculosis surgery, many factors can lead to surgical site infection (SSI). No definitive reports of local streptomycin irrigation of the lesion and SSI of spinal tuberculosis have been seen. This study analyzed data related to surgical site infections (SSI) after the treatment of spinal tuberculosis using this regimen.

Methods

In this study, 31 were in the observation group (streptomycin flush) and 34 in the control group (no streptomycin flush). All patients received the same standard of perioperative care procedures. General information, operative time, intraoperative bleeding, ESR and CRP at one week postoperatively, time on antibiotics, total drainage, days in hospital, incision infection rate and secondary debridement rate were compared between the two groups.

Results

Patients in both groups completed the surgery successfully. The ESR and CRP levels in the observation group were lower than those in the control group one week after surgery (p < 0.05); the duration of postoperative antibiotics and hospital stay were lower than those in the control group (p < 0.05); the incidence of SSI in the two groups was 5.88% and 6.45% respectively, with no significant difference (p > 0.05).

Conclusion

The use of topical streptomycin irrigation of the lesion during surgical procedures for spinal tuberculosis had no significant effect on the incidence of SSI, however, it helped to control the level of infection in the postoperative period and reduced the length of time patients had to use postoperative antibiotics and the number of days they stayed in hospital. Future prospective randomised controlled trials in more centres and larger samples are recommended.
Linkage and association of variants in the dopamine receptor 2 gene (DRD2) with polycystic ovary syndrome
Authors: Amin Mutaz , Horst Nicholas , Gragnoli Claudia
Published: August 2023

Polycystic ovarian syndrome (PCOS) is a disorder with a foundation of neuroendocrine dysfunction, characterized by increased gonadotropin-releasing hormone (GnRH) pulsatility, which is antagonized by dopamine. The dopamine receptor 2 (DRD2), encoded by theDRD2gene, has been shown to mediate dopamine’s inhibition of GnRH neuron excitability through pre- and post-synaptic interactions in murine models. Further, DRD2 is known to mediate prolactin (PRL) inhibition by dopamine, and high blood level of PRL have been found in more than one third of women with PCOS. We recently identifiedPRLas a gene contributing to PCOS risk and reportedDRD2conferring risk for type 2 diabetes and depression, which can both coexist with PCOS. Given DRD2 mediating dopamine’s action on neuroendocrine profiles and association with metabolic-mental states related to PCOS, polymorphisms inDRD2may predispose to development of PCOS. Therefore, we aimed to investigate whetherDRD2variants are in linkage to and/or linkage disequilibrium (i.e., linkage and association) with PCOS in Italian families. In 212 Italian families, we tested 22 variants within theDRD2gene for linkage and linkage disequilibrium with PCOS. We identified five novel variants significantly linked to the risk of PCOS. This is the first study to identifyDRD2as a risk gene in PCOS, however, functional studies are needed to confirm these results.
Maast: genotyping thousands of microbial strains efficiently
Authors: Shi Zhou Jason , Nayfach Stephen , Pollard Katherine S.
Published: August 2023

Existing single nucleotide polymorphism (SNP) genotyping algorithms do not scale for species with thousands of sequenced strains, nor do they account for conspecific redundancy. Here we present a bioinformatics tool, Maast, which empowers population genetic meta-analysis of microbes at an unrivaled scale. Maast implements a novel algorithm to heuristically identify a minimal set of diverse conspecific genomes, then constructs a reliable SNP panel for each species, and enables rapid and accurate genotyping using a hybrid of whole-genome alignment and k-mer exact matching. We demonstrate Maast’s utility by genotyping thousands of Helicobacter pylori strains and tracking SARS-CoV-2 diversification.
Organisational models supported by technology for the management of diabetic disease and its complications in a diabetic clinic setting: study protocol for a randomised controlled trial targeting type 2 diabetes individuals with non-ideal glycaemic values (Telemechron study)
Authors: Giovanazzi Alexia , Gios Lorenzo , Mastellaro Marina , Gentilini Maria Adalgisa , Valent Francesca , Condini Sara , Bincoletto Giorgia , Bacchiega Alessandro , Zorzi Andrea , Malfatti Giulia , Perini Francesca , Eccher Claudio , Marchesoni Michele , Dall’Alda Marlene , Orrasch Massimo , Conforti Diego , Inchiostro Sandro
Published: August 2023

Introduction

Type 2 diabetes mellitus (T2DM) is a non-communicable disease representing one of the most serious public health challenges of the twenty-first century. Its incidence continues to rise in both developed and developing countries, causing the death of 1.5 million people every year. The use of technology (e.g. smartphone application—App) in the health field has progressively increased as it has been proved to be effective in helping individuals manage their long-term diseases. Therefore, it has the potential to reduce the use of health service and its related costs. The objective of this study is to evaluate the impact of using a digital platform called “TreC Diabete” embedded into a novel organisational asset targeting poorly controlled T2DM individuals in the Autonomous Province of Trento (PAT), Italy.

Methods

This trial was designed as a multi-centre, open-label, randomised, superiority study with two parallel groups and a 1:1 allocation ratio. Individuals regularly attending outpatient diabetes clinics, providing informed consent, are randomised to be prescribed TreC Diabete platform as part of their personalised care plan. Healthcare staff members will remotely assess the data shared by the participants through the App by using a dedicated online medical dashboard. The primary end-point is the evaluation of the Hb1Ac level at 12-month post-randomisation. Data will be analysed on an intention-to-treat (ITT) basis.

Discussion

This trial is the first conducted in the PAT area for the use of an App specifically designed for individuals with poorly controlled T2DM. If the effects of introducing this specific App within a new organisational asset are positive, the digital platform will represent a possible way for people diagnosed with T2DM to better manage their health in the future. Results will be disseminated through conferences and peer-reviewed journals once the study is completed.

Trial registration

ClinicalTrials.gov NCT05629221. Registered on November 29, 2022, prior start of inclusion.
Mitogenomic phylogenies suggest the resurrection of the subfamily Porrocaecinae and provide insights into the systematics of the superfamily Ascaridoidea (Nematoda: Ascaridomorpha), with the description of a new species of Porrocaecum
Authors: Gu Xiao-Hong , Guo Ning , Chen Hui-Xia , Sitko Jiljí , Li Lin-Wei , Guo Bing-Qian , Li Liang
Published: August 2023

Background

The family Toxocaridae is a group of zooparasitic nematodes of veterinary, medical and economic significance. However, the evolutionary relationship of Porrocaecum and Toxocara, both genera currently classified in Toxocaridae, and the monophyly of the Toxocaridae remain under debate. Moreover, the validity of the subgenus Laymanicaecum in the genus Porrocaecum is open to question. Due to the scarcity of an available genetic database, molecular identification of Porrocaecum nematodes is still in its infancy.

Methods

A number of Porrocaecum nematodes collected from the Eurasian marsh harrier Circus aeruginosus (Linnaeus) (Falconiformes: Accipitridae) in the Czech Republic were identified using integrated morphological methods (light and scanning electron microscopy) and molecular techniques (sequencing and analyzing the nuclear 18S, 28S and ITS regions). The complete mitochondrial genomes of the collected nematode specimens and of Porrocaecum (Laymanicaecum) reticulatum (Linstow, 1899) were sequenced and annotated for the first time. Phylogenetic analyses of ascaridoid nematodes based on the amino acid sequences of 12 protein-coding genes of mitochondrial genomes were performed using maximum likelihood and Bayesian inference.

Results

A new species of Porrocaecum, named P. moraveci n. sp., is described based on the morphological and genetic evidence. The mitogenomes of P. moraveci n. sp. and P. reticulatum both contain 36 genes and are 14,517 and 14,210 bp in length, respectively. Comparative mitogenomics revealed that P.moraveci n. sp. represents the first known species with three non-coding regions and that P. reticulatum has the lowest overall A + T content in the mitogenomes of ascaridoid nematodes tested to date. Phylogenetic analyses showed the representatives of Toxocara clustered together with species of the family Ascarididae rather than with Porrocaecum and that P. moraveci n. sp. is a sister to P. reticulatum.

Conclusions

The characterization of the complete mitochondrial genomes of P. moraveci n. sp. and P. reticulatum is reported for the first time. Mitogenomic phylogeny analyses indicated that the family Toxocaridae is non-monophyletic and that the genera Porrocaecum and Toxocara do not have an affinity. The validity of the subgenus Laymanicaecum in Porrocaecum was also rejected. Our results suggest that: (i) Toxocaridae should be degraded to a subfamily of the Ascarididae that includes only the genus Toxocara; and (ii) the subfamily Porrocaecinae should be resurrected to include only the genus Porrocaecum. The present study enriches the database of ascaridoid mitogenomes and provides a new insight into the systematics of the superfamily Ascaridoidea.

Graphical Abstract
Exosomes derived from mir-214-3p overexpressing mesenchymal stem cells promote myocardial repair
Authors: Zhu Wenwu , Wang Qingjie , Zhang Jian , Sun Ling , Hong Xiu , Du Wei , Duan Rui , Jiang Jianguang , Ji Yuan , Wang Haoran , Han Bing
Published: August 2023

Aims

Exosomes are known as nanovesicles that are naturally secreted, playing an essential role in stem-mediated cardioprotection. This study mainly focused on investigating if exosomes derived from miR-214 overexpressing mesenchymal stem cells (MSCs) show more valid cardioprotective ability in a rat model of acute myocardial infarction (AMI) and its potential mechanisms.

Methods

Exosomes were isolated from control MSCs (Ctrl-Exo) and miR-214 overexpressing MSCs (miR-214
OE
-Exo) and then they were delivered to cardiomyocytes and endothelial cells in vitro under hypoxia and serum deprivation (H/SD) condition or in vivo in an acutely infarcted Sprague-Dawley rat heart. Regulated genes and signal pathways by miR-214
OE
-Exo treatment were explored using western blot analysis and luciferase assay.

Results in vitro

, miR-214
OE
-Exo enhanced migration, tube-like formation in endothelial cells. In addition, miR-214
OE
-Exo ameliorated the survival of cardiomyocytes under H/SD. In the rat AMI model, compared to Ctrl-Exo, miR-214
OE
-Exo reduced myocardial apoptosis, and therefore reduced infarct size and improved cardiac function. Besides, miR-214
OE
-Exo accelerated angiogenesis in peri-infarct region. Mechanistically, we identified that exosomal miR-214-3p promoted cardiac repair via targeting PTEN and activating p-AKT signal pathway.

Conclusion

Exosomes derived from miR-214 overexpressing MSCs have greatly strengthened the therapeutic efficacy for treatment of AMI by promoting cardiomyocyte survival and endothelial cell function.

Graphical abstract
Hydraulic fracturing distributed acoustic sensing monitoring data source mechanism inversion: A Hessian-based method
Authors: Wu Shaojiang , Wang Yibo , Liang Xing
Published: August 2023

Distributed acoustic sensing (DAS) microseismic monitoring during hydraulic fracturing provides microseismic data with high spatial samplings for fracturing zones. However, sources located perpendicular to the single horizontal well of the DAS acquisition system have limited source-receiver geometries with extremely poor azimuthal coverage, resulting in high uncertainty in source mechanism inversion. To address this problem, we introduce the Hessian matrix, which governs the blurring effect caused by the source-receiver geometry, into the DAS microseismic source mechanism inversion. Our Hessian-based source mechanism inversion method consists of three main steps: (1) construct the Hessian matrix of the source mechanism based on the source-receiver geometry, (2) obtain an initial source mechanism using a conventional source mechanism inversion method, and (3) update the initial source mechanism using a Hessian-based [Formula: see text]-regularized least-squares algorithm. We assess the robustness of our method using synthetic DAS microseismic data with the consideration of noise, source location error, and different regularization parameters, and we compare the results with those of the conventional method. The results demonstrate that the Hessian-based method has a remarkable ability to mitigate the blurring effect of the Hessian matrix caused by limited DAS source-receiver geometry with poor azimuthal coverage, thereby reducing the uncertainty of the inverted source mechanism even in the presence of real noise and/or source location error. Finally, we use our method to invert the source mechanism of a real DAS microseismic event acquired during hydraulic fracturing. Our Hessian-based method provides low uncertainty in the source mechanism inversion of the real DAS microseismic data.
Margin to Depth of Invasion Ratio: A Significant Predictor of Survival in Patients With Oral Cancer
Authors: Sultania Mahesh , Chaudhary Itisha , Jain Priyansh , Ghalige Hemanth , Rajan Dipin , G Sudhakar , K Raghuram , Muduly Dillip , Barik Sandip , Pathak Mona , Adhya Amit , Kar Madhabananda , Majumdar Saroj
Published: August 2023

PURPOSE

A common definition of a clear margin (≥5 mm) in oral squamous cell carcinoma (OSCC) for all stages is a subject of controversy. Studies have shown that even 1- and 2-mm margins are adequate, and few studies have identified dynamic resection margin as a criterion. We aimed to study the margin to depth of invasion ratio (MDR), margin to tumor thickness ratio (MTR), and margin to tumor size ratio (MSR) as prognostic markers for survival. Notably, to our knowledge, this is the first study to evaluate the role of MDR in OSCC.

METHODS

A prospectively maintained head and neck cancer database was analyzed from January 2017 to February 2023. The MDR, MTR, and MSR were calculated for each patient. Survival outcomes were analyzed using the Cox proportional model and the Kaplan-Meier method. Akaike's information criterion (AIC) and Bayesian information criterion (BIC) were used to compare different ratio models. X-tiles software was used to identify the optimal cutoff value of MDR.

RESULTS

Two hundred eighty patients in the database were assessed, of which 123 eligible patients were enrolled in the study. MDR was an independent predictor of disease-free survival (DFS) on multivariate analysis. The MDR model had the lowest values on AIC and BIC analyses. A cutoff value of 0.5 for MDR showed a significant correlation with DFS and overall survival.

CONCLUSION

MDR was the best predictor of recurrence of all the three ratios studied. The minimum safe surgical margin can be calculated by multiplying the depth of invasion by 0.5. This study signifies the role of dynamic resection margin criteria on the basis of MDR in defining clear margins.
Glucagon-Like Peptide 1 Analogues as Adjunctive Therapy for Patients With Type 1 Diabetes: An Updated Systematic Review and Meta-analysis
Authors: Park Jeayoung , Ntelis Spyridon , Yunasan Elvina , Downton Katherine D , Yip Terry Cheuk-Fung , Munir Kashif M , Haq Nowreen
Published: August 2023

Context

Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce.

Objective

We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM.

Method

PubMed, EMBASE, Cochrane Central, and Scopus databases were searched for randomized controlled trials up to December 2022. Efficacy outcomes were A1c level, body weight, and total daily insulin (TDI) after ≥12 weeks of GLP-1 therapy. We also assessed 12 different adverse outcomes. Subgroup analysis was done for newly diagnosed or C-peptide positive (C-pos) patients. We report the certainty of evidence based on the GRADE assessment tool.

Results

A total of 24 studies using 4 different GLP-1 analogues with a total of 3377 patients were included. Liraglutide had the most substantial evidence with effect sizes on A1c (−0.09%/mg), weight (−2.2 kg/mg), and TDI (−4.32 IU/mg). Liraglutide dose was the greatest predictor of greater average weight loss and TDI decrease but was associated with higher odds of nausea (OR 6.5; 95% CI, 5.0-8.4) and ketosis (OR 1.8; 95% CI, 1.1-2.8). Odds of severe (OR 0.67; 95% CI, 0.43-1.04) or symptomatic hypoglycemia (OR 0.89; 95% CI, 0.53-1.51) were not significantly elevated. Among C-pos patients, greater A1c decrease (−0.51% vs −0.28%) but similar weight loss and TDI were seen. Effect sizes for exenatide were similar, but studies had higher risk of bias and safety data were sparse.

Conclusion

Our meta-analysis supports therapeutic benefits of liraglutide for patients with T1DM mainly for weight loss and insulin dose reduction. Newly diagnosed or C-pos patients do not appear to experience greater weight loss benefits.
Obesity-Related Hypogonadism in Women
Authors: Eng Pei Chia , Phylactou Maria , Qayum Ambreen , Woods Casper , Lee Hayoung , Aziz Sara , Moore Benedict , Miras Alexander D , Comninos Alexander N , Tan Tricia , Franks Steve , Dhillo Waljit S , Abbara Ali
Published: August 2023

Obesity-related hypogonadotropic hypogonadism is a well-characterized condition in men (termed male obesity-related secondary hypogonadism; MOSH); however, an equivalent condition has not been as clearly described in women. The prevalence of polycystic ovary syndrome (PCOS) is known to increase with obesity, but PCOS is more typically characterized by increased gonadotropin-releasing hormone (GnRH) (and by proxy luteinizing hormone; LH) pulsatility, rather than by the reduced gonadotropin levels observed in MOSH. Notably, LH levels and LH pulse amplitude are reduced with obesity, both in women with and without PCOS, suggesting that an obesity-related secondary hypogonadism may also exist in women akin to MOSH in men. Herein, we examine the evidence for the existence of a putative non-PCOS “female obesity-related secondary hypogonadism” (FOSH). We précis possible underlying mechanisms for the occurrence of hypogonadism in this context and consider how such mechanisms differ from MOSH in men, and from PCOS in women without obesity. In this review, we consider relevant etiological factors that are altered in obesity and that could impact on GnRH pulsatility to ascertain whether they could contribute to obesity-related secondary hypogonadism including: anti-Müllerian hormone, androgen, insulin, fatty acid, adiponectin, and leptin. More precise phenotyping of hypogonadism in women with obesity could provide further validation for non-PCOS FOSH and preface the ability to define/investigate such a condition.