bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of physiotherapeutic procedures on the bioelectric activity of the masseter muscle and the range of motion of the temporomandibular joints in the female population with chronic pain: a randomized controlled trial
Authors: Gębska Magdalena , Dalewski Bartosz , Pałka Łukasz , Kiczmer Paweł , Kołodziej Łukasz
Published: November 2023

Introduction

Physical therapy (PT) methods applied in dentistry are increasingly discussed nowadays. Taking into account a rapidly growing number of temporomandibular disorders (TMDs) and orofacial pain patients, it is reasonable to determine which of the available physiotherapeutic (PT) methods are more effective than others, especially in terms of their possible analgesic and myorelaxant effects.

Objective

To assess manual and physical factors influencing pain reduction or elimination and increased muscle tension in patients with TMD; yet the influence of the applied forms of PT on the range of motion (ROM) of temporomandibular joints (TMJ).

Material and methods

A randomized, parallel-group, RCT, single-blind, equi-randomized (1:1) study was conducted in DC/TMD Group Ib patients (20–45 years of age). An experimental group (G1, n = 104) and a control group without TMD (G2, n = 104) were created according to CONSORT guidelines. Diagnostic measurements were performed in both groups (mass sEMG, temporomandibular joint range of motion-ROM, pain intensity - NRS). Group G1 was randomly divided (envelope method) into 4 therapeutic groups, in which therapy was carried out for 10 days: magnetostimulation (MS), magnetoledotherapy (MLE), magnetolaserotherapy (MLA), manual therapy (MT). Each time after the therapy, ROM and NRS measurements were performed, and after the 5th and 10th day sEMG.

Results

Statistically significant differences were found in the sEMG values of the masseter muscles, TMJ ROM and the pain intensity in G1 and G2 (p < 0.00). The largest decrease in sEMG (% MVC) of the masseter muscle occurred in the subgroup in which the manual therapy (MT) procedures were applied, p < 0.000. There was no clinically significant difference in and between other subgroups. There was a distinct mandible ROM increase noted in the MT group, with minimal changes in the MLA and MLE groups and no changes in the MS group. There was a clear increase in the lateral mobility of both right and left TMJ in the MT group. There were no differences in the course of the study in the MS group, and slight increases in the MLA and MLE groups. In the case of pain measurements, the greatest decrease in pain intensity was observed in the MT subgroup.

Conclusions

According to our results manual therapy is an effective form of treatment in patients with pain, increased masticatory muscle tension and limitation in mandible ROM. Dental physiotherapy should become an integral part of multimodal TMD patients’ treatment.
Circ_0099630 knockdown alleviates lipopolysaccharide-induced injuries of human periodontal ligament cells through the inhibition of TLR4 by releasing miR-409-3p
Authors: Qi Hongyan , Han Bing , Che Jin
Published: November 2023

Background

Periodontitis triggers tooth loss and affects the health of population worldwide. Emerging evidence hints that circular RNAs (circRNAs) are involved in various diseases, including periodontitis. This study aimed to investigate the role of circ_0099630 in the progression of periodontitis.

Methods

Periodontitis cell model was constructed by treating human periodontal ligament cells (HPDLCs) with lipopolysaccharide (LPS). Quantitative real-time PCR was used to analyze the expression of circ_0099630, microRNA-409-3p (miR-409-3p) and toll-like receptor 4 (TLR4) mRNA. Western blot was used for detecting protein levels of TLR4, cleaved-caspase 3, Bcl-2, CyclinD1 and NF-κB signaling markers. For function analyses, cell proliferation was assessed by CCK-8 assay and EdU assay. The releases of pro-inflammation factors were monitored by ELISA kits. The potential relationship between miR-409-3p and circ_0099630 or TLR4 was verified by dual-luciferase reporter assay, RIP assay and pull-down assay.

Results

The expression of circ_0099630 and TLR4 was elevated in periodontitis patients and LPS-treated HPDLCs. LPS induced HPDLC proliferation inhibition, apoptosis and inflammatory responses, while circ_0099630 knockdown or TLR4 knockdown alleviated these injuries. Besides, TLR4 overexpression reversed the inhibitory effect of circ_0099630 knockdown on LPS-induced HPDLC injuries. Mechanism analysis showed that circ_0099630 positively regulated TLR4 expression by acting as miR-409-3p sponge. MiR-409-3p restoration largely ameliorated LPS-induced HPDLC injuries by depleting TLR4. Moreover, LPS activated the NF-κB signaling pathway, while circ_0099630 knockdown inhibited the activity of NF-κB signaling via the miR-409-3p/TLR4 axis.

Conclusion

Circ_0099630 knockdown relieved LPS-induced HPDLC injury by miR-409-3p/TLR4 axis, suggesting that circ_0099630 might be a potential target for periodontitis treatment.
Barriers and enablers for oral health promotion programs amongst primary healthcare stakeholders in Qatar – a qualitative investigation
Authors: Alkhtib Asmaa Othman , Ali Kamran , Sajnani Anand K. , Anweigi Lamyia
Published: November 2023

Background

Oral health of preschool children remains a concern globally. Primary healthcare providers are in a vital position to support preventive oral care programmes. This study explored current practices, perception and barriers of primary health care professionals towards oral health promotion program of children in Qatar.

Methods

The qualitative research used focus group discussions and interviewed a total of 108 participants that were audio recorded and transcribed verbatim. Four major themes emerged and were analysed to explore contextual patterns within the data.

Results

Participants acknowledged the high prevalence of caries in children and identified the causes in the local context which included parental practices, poor dietary habits, impact of culture lack of oral health knowledge, limitations in the healthcare system, and negative role of the media. However, complex barriers were exposed, including lack of time and ownership, system coordination between organizations, and lack of policy.

Conclusion

Health professionals and bureaucrats involved in decision-making held a positive attitude towards oral health prevention programs and were enthusiastic to initiate and support these programs.
Evaluation of implants in smoking and non-smoking patients with peri-implant disease risk analysis and esthetic scores: an observational study
Authors: Şahin Tuğba
Published: November 2023

Background

This study examined how smoking affects esthetics, peri-implant health, gingiva around the implant, and implant disease risk assessment in patients with implants.

Methods

The study included two hundred ninety-eight implants of systemically healthy patients aged between 38 and 62 who applied to the Periodontology Clinic and whose functionally prosthesis-loaded implants had been at least six months and at most five years old. Implants of patients with bruxism were not included in the study. Implants are divided into two according to the patient’s smoking. Vestibule depth around the implant, keratinized gingival thickness and width, gingival recession, bleeding on probing, pocket depth, and gingival index by a sole clinician. The pink esthetic score, peri-implant disease risk assessment, and implant health scale were also examined to measure implant esthetics and success.

Results

There was a statistically significant difference in the implant disease risk assesment scores for the examined implants of smokers and nonsmokers (p < 0.05). People who had peri-implantitis had higher implant disease risk assesment score levels. The dental implant health scale revealed a statistically significant difference (p < 0.05) in the likelihood of implant disease. According to the dental implant health scale, dental implants were 100% successful for non-smokers. There was a significant difference in the keratinized gingiva width between smokers and nonsmokers (p < 0.05). The results of the study showed that nonsmokers had a wider keratinized gingiva.

Conclusions

Research has demonstrated that the act of smoking has the potential to jeopardize the long-term survival of dental implants and the surrounding peri-implant tissues. The results of this study indicate that it would be advisable for dentists to provide guidance to their patients on smoking cessation and to monitor any alterations in behavior closely. Furthermore, it would be advantageous for dental professionals to elucidate the impact of smoking on the susceptibility of smokers to peri-implant disease.
Dental public health education in Egypt: a cross-sectional survey
Authors: Gouda Haya , Virtanen Jorma I. , El Tantawi Maha
Published: November 2023

Background and aim

Dental Public Health (DPH) education prepares future workforce to promote positive oral health behaviors, prevent oral diseases, and monitor disease distribution and trends taking into considerations best practices, needs and available resources. Scarce information is available about dental education in African countries and Egypt has the greatest number of dental schools in Africa. This study assessed the undergraduate DPH education in Egyptian universities including topics taught, methods of teaching, assessment, and the academics’ specialties.

Methods

A survey targeted 43 Egyptian universities with Bachelor of Dentistry (BDS) programs identified on the website of the Supreme Council of Egyptian Universities in 2022. Thirty-six deans could be reached by post and/ or email. The survey appraised the school profile and capacity, and methods of teaching and assessment in DPH courses in undergraduate dental programs. The survey also inquired who taught DPH courses and what was covered in the courses. Descriptive statistics were displayed.

Results

We received 21 (58.3%) responses from 36 deans/ senior officials. Of the universities, 52.4% were private and 47.6% were public. Most participants reported that DPH courses in BDS programs were taught by Pediatric Dentistry academics (71.4%) and DPH academics (57.1%) in 3rd, 4th and 5th years of the 5-year BDS programs. Teaching DPH consisted of face-to-face lectures (100%) and seminars (95.2%) and assessment included written exams with close ended questions (95.2%) and open-ended questions (71.4%). Twenty schools reported teaching the definition of DPH, definition of oral health, and determinants of oral diseases. Nine schools addressed the planning of oral health services and five schools taught about remuneration and payment systems.

Conclusion

Teaching and assessment of DPH in Egyptian dental schools use traditional methods with limited active engagement of the students. Variations among the schools exist in the DPH topics covered and most instructors were not primarily specialized in DPH. Development of dental/ oral health services calls for more emphasis on DPH education in the curriculum in Egypt.
Association of the affordable care act with racial and ethnic disparities in uninsured emergency department utilization
Authors: Ukert Benjamin , Giannouchos Theodoros V.
Published: November 2023

Background

Disparities in uninsured emergency department (ED) use are well documented. However, a comprehensive analysis evaluating how the Affordable Care Act (ACA) may have reduced racial and ethnic disparities is lacking. The goal was to assess the association of the ACA with racial and ethnic disparities in uninsured ED use.

Methods

This study used data from the Healthcare Cost and Utilization Project (HCUP) State Emergency Department Databases (SEDD) for Georgia, Florida, Massachusetts, and New York from 2011 to 2017. Participants include non-elderly adults between 18 and 64 years old. Outcomes include uninsured rates of ED visits by racial and ethnic groups and stratified by medical urgency using the New York University ED algorithm. Visits were aggregated to year-quarter ED visits per 100,000 population and stratified for non-Hispanic White, non-Hispanic Black, and Hispanic non-elderly adults. Quasi-experimental difference-in-differences and triple differences regression analyses to identify the effect of the ACA and the separate effect of the Medicaid expansion were used comparing uninsured ED visits by race and ethnicity groups pre-post ACA.

Results

The ACA was associated with a 14% reduction in the rate of uninsured ED visits per 100,000 population (from 10,258 pre-ACA to 8,877 ED visits per 100,000 population post-ACA) overall. The non-Hispanic Black compared to non-Hispanic White disparity decreased by 12.4% (-275.1 ED visits per 100,000) post-ACA. About 60% of the decline in the Black-White disparity was attributed to disproportionate declines in ED visit rates for conditions classified as not-emergent (-93.2 ED visits per 100,000), and primary care treatable/preventable (-64.1 ED visits per 100,000), while the disparity in ED visit rates for injuries and not preventable conditions also declined (-106.57 ED visits per 100,000). All reductions in disparities were driven by the Medicaid expansion. No significant decrease in Hispanic-White disparity was observed.

Conclusions

The ACA was associated with fewer uninsured ED visits and reduced the Black-White ED disparity, driven mostly by a reduction in less emergent ED visits after the ACA in Medicaid expansion states. Disparities between Hispanic and non-Hispanic White adults did not decline after the ACA. Despite the positive momentum of declining disparities in uninsured ED visits, disparities, especially among Black people, remain.
Evidence of malarial chemoprophylaxis among travellers who died from malaria: a systematic review and meta-analysis
Authors: Kotepui Manas , Kotepui Kwuntida Uthaisar , Masangkay Frederick Ramirez , Wilairatana Polrat
Published: November 2023

Background

Chemoprophylaxis is a prevention method for malaria during travel in malaria-endemic countries. This study aimed to collate and synthesize the evidence of malarial chemoprophylaxis among malaria death cases.

Methods

Studies documenting malarial chemoprophylaxis related to malaria deaths were searched in PubMed, Scopus, MEDLINE, Embase, and CENTRAL until 3 July 2022. The pooled proportion of malarial chemoprophylaxis among death cases was synthesized using logit transformation and back transformation to a proportion performed using generalized linear mixed models. The pooled log odds ratio (log-OR) with a 95% confidence interval (CI) of malarial chemoprophylaxis in death cases compared to survivors were synthesized.

Results

Fifty-eight studies were included in the systematic review and the meta-analysis. Of 602 pooled malaria death cases, the number of patients who took chemoprophylaxis was 187 (30%) (95% CI 22–40, P < 0.01, 58 studies), and those who took adequate chemoprophylaxis were 24 (5%) (95% CI 2–13, P < 0.01, 42 studies). A comparable log-OR of underwent chemoprophylaxis was observed between malaria death cases and survivors (P = 0.94, pooled log-OR: − 0.02, 95% CI − 0.46–0.42, I2: 0%, 17 studies). Similarly, a comparable log-OR of adequate chemoprophylaxis was identified between malaria death cases and survivors (P = 0.15, pooled log-OR: 0.83, 95% CI − 0.30–1.97, I2: 47.08%, 11 studies).

Conclusions

Among the studies where malarial chemoprophylaxis was reported, approximately 30% of malaria death cases had taken such prophylaxis. Notably, only 5% of these cases adhered fully or adequately to the recommended chemoprophylactic regimen. However, the analysis did not reveal a significant difference in the odds of malarial chemoprophylaxis between malaria death cases and survivors.
Spatial mapping of tumor heterogeneity in whole-body PET–CT: a feasibility study
Authors: Jönsson Hanna , Ahlström Håkan , Kullberg Joel
Published: November 2023

Background

Tumor heterogeneity is recognized as a predictor of treatment response and patient outcome. Quantification of tumor heterogeneity across all scales may therefore provide critical insight that ultimately improves cancer management.

Methods

An image registration-based framework for the study of tumor heterogeneity in whole-body images was evaluated on a dataset of 490 FDG-PET–CT images of lung cancer, lymphoma, and melanoma patients. Voxel-, lesion- and subject-level features were extracted from the subjects’ segmented lesion masks and mapped to female and male template spaces for voxel-wise analysis. Resulting lesion feature maps of the three subsets of cancer patients were studied visually and quantitatively. Lesion volumes and lesion distances in subject spaces were compared with resulting properties in template space. The strength of the association between subject and template space for these properties was evaluated with Pearson’s correlation coefficient.

Results

Spatial heterogeneity in terms of lesion frequency distribution in the body, metabolic activity, and lesion volume was seen between the three subsets of cancer patients. Lesion feature maps showed anatomical locations with low versus high mean feature value among lesions sampled in space and also highlighted sites with high variation between lesions in each cancer subset. Spatial properties of the lesion masks in subject space correlated strongly with the same properties measured in template space (lesion volume, R = 0.986, p < 0.001; total metabolic volume, R = 0.988, p < 0.001; maximum within-patient lesion distance, R = 0.997, p < 0.001). Lesion volume and total metabolic volume increased on average from subject to template space (lesion volume, 3.1 ± 52 ml; total metabolic volume, 53.9 ± 229 ml). Pair-wise lesion distance decreased on average by 0.1 ± 1.6 cm and maximum within-patient lesion distance increased on average by 0.5 ± 2.1 cm from subject to template space.

Conclusions

Spatial tumor heterogeneity between subsets of interest in cancer cohorts can successfully be explored in whole-body PET–CT images within the proposed framework. Whole-body studies are, however, especially prone to suffer from regional variation in lesion frequency, and thus statistical power, due to the non-uniform distribution of lesions across a large field of view.
Epidemiology, risk areas and macro determinants of gastric cancer: a study based on geospatial analysis
Authors: Huang Binjie , Liu Jie , Ding Feifei , Li Yumin
Published: November 2023

Background

Both incidence and mortality of gastric cancer in Gansu rank first in china, this study aimed to describe the recent prevalence of gastric cancer and explore the social and environmental determinants of gastric cancer in Gansu Province.

Methods

The incidence of gastric cancer in each city of Gansu Province was calculated by utilizing clinical data from patients with gastric cancer (2013–2021) sourced from the medical big data platform of the Gansu Province Health Commission, and demographic data provided by the Gansu Province Bureau of Statistics. Subsequently, we conducted joinpoint regression analysis, spatial auto-correlation analysis, space–time scanning analysis, as well as an exploration into the correlation between social and environmental factors and GC incidence in Gansu Province with Joinpoint_5.0, ArcGIS_10.8, GeoDa, SaTScanTM_10.1.1 and GeoDetector_2018.

Results

A total of 75,522 cases of gastric cancer were included in this study. Our findings suggested a significant upward trend in the incidence of gastric cancer over the past nine years. Notably, Wuwei, Zhangye and Jinchang had the highest incidence rates while Longnan, Qingyang and Jiayuguan had the lowest. In spatial analysis, we have identified significant high-high cluster areas and delineated two high-risk regions as well as one low-risk region for gastric cancer in Gansu. Furthermore, our findings suggested that several social and environmental determinants such as medical resource allocation, regional economic development and climate conditions exerted significant influence on the incidence of gastric cancer.

Conclusions

Gastric cancer remains an enormous threat to people in Gansu Province, the significant risk areas, social and environmental determinants were observed in this study, which may improve our understanding of gastric cancer epidemiology and help guide public health interventions in Gansu Province.
Hypoxic preconditioned MSCs-derived small extracellular vesicles for photoreceptor protection in retinal degeneration
Authors: Sun Yuntong , Sun Yuntao , Chen Shenyuan , Yu Yifan , Ma Yongjun , Sun Fengtian
Published: November 2023

Photoreceptor apoptosis is an important pathogenesis of retinal degeneration and a primary cause of vision loss with limited treatment methods. Mesenchymal stem/stromal cells-derived small extracellular vesicles (MSC-sEVs) have shown therapeutic value in various ocular disorders. Recent studies have revealed that hypoxic preconditioning can improve the effectiveness of MSC-sEVs in tissue regeneration. However, whether hypoxic preconditioned MSC-sEVs (Hyp-sEVs) exert superior effects on photoreceptor protection relative to normoxic conditioned MSC-sEVs (Nor-sEVs) remains unclear. Here, we reported that Hyp-sEVs further improved retinal structure, recovered retinal function, and suppressed photoreceptor apoptosis in N-methyl-N-nitrosourea (MNU)-induced mouse model compared with Nor-sEVs. Hyp-sEVs also exhibited enhanced anti-apoptotic roles in MNU-provoked 661 W cell injury in vitro. We then analyzed the protein profiles of Nor-sEVs and Hyp-sEVs by LC-MS/MS and found that growth-associated protein 43 (GAP43) was enriched in Hyp-sEVs. The knockdown of GAP43 abolished the retinal therapeutic effects of Hyp-sEVs. Mechanistically, hypoxic stimulation-induced hypoxia-inducible factor-1α (HIF-1α) activation was responsible for preventing tripartite motif-containing protein 25 (TRIM25)-mediated GAP43 ubiquitination and degradation, leading to the upregulation of GAP43 in Hyp-sEVs. Together, our findings uncover the efficacy and mechanism of Hyp-sEVs-based photoreceptor protection and highlight the potential of Hyp-sEVs as optimized therapeutics for retinal degeneration.

Graphical abstract
Outcomes of surgery and subsequent therapy for central nervous system oligoprogression in EGFR-mutated NSCLC patients
Authors: Perng Pang-Shuo , Hsu Heng-Juei , Lee Jung-Shun , Wang Liang-Chao , Huang Chih-Yuan , Tien Chih-Hao , Lai Yu-Hsuan , Su Po-Lan , Hsu Hao-Hsiang , Chen Liang-Yi , Lee Po-Hsuan
Published: November 2023

Background

Oligoprogression is an emerging issue in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the surgical treatment for central nervous system (CNS) oligoprogression is not widely discussed. We investigated the outcomes of craniotomy with adjuvant whole-brain radiotherapy (WBRT) and subsequent therapies for CNS oligoprogression in patients with EGFR-mutated NSCLC.

Methods

NSCLC patients with CNS oligoprogression were identified from a tertiary medical center. The outcomes of surgery with adjuvant WBRT or WBRT alone were analyzed, along with other variables. Overall survival and progression-free survival were analyzed using the log-rank test as the primary and secondary endpoints. A COX regression model was used to identify the possible prognostic factors.

Results

Thirty-seven patients with CNS oligoprogression who underwent surgery or WBRT were included in the study after reviewing 728 patients. Twenty-one patients underwent surgery with adjuvant WBRT, and 16 received WBRT alone. The median overall survival for surgery and WBRT alone groups was 43 (95% CI 17–69) and 22 (95% CI 15–29) months, respectively. Female sex was a positive prognostic factor for overall survival (OR 0.19, 95% CI 0.06–0.57). Patients who continued previous tyrosine kinase inhibitors (OR 3.48, 95% CI 1.06–11.4) and induced oligoprogression (OR 3.35, 95% CI 1.18–9.52) were associated with worse overall survival. Smoking history (OR 4.27, 95% CI 1.54–11.8) and induced oligoprogression (OR 5.53, 95% CI 2.1–14.7) were associated with worse progression-free survival.

Conclusions

Surgery combined with adjuvant WBRT is a feasible treatment modality for CNS oligoprogression in patients with EGFR-mutated NSCLC. Changing the systemic-targeted therapy after local treatments may be associated with improved overall survival.
CircTENM3 inhibites tumor progression via the miR-558/RUNX3 axis in prostate cancer
Authors: Lu Lingxiang , Wang Fei , Chen Jianchun , Zhao Chunchun , Guo Shuai , Dong Da , Jiang Minjun , Huang Yuhua
Published: November 2023

Background

Prostate cancer (PCa) is currently acknowledged as the second most widespread cancer among men worldwide. Yet, the lack of dependable diagnostic biomarkers and therapeutic targets has presented considerable hurdles to the progression of prostate cancer treatment. Circular RNAs are implicated in the pathogenesis of numerous diseases, positioning them as promising biomarkers for diverse medical conditions. This study aims to uncover a specific circRNA that could serve as a diagnostic and therapeutic target for detecting and treating PCa.

Methods

The change of circTENM3 expression levels in PCa was detected by qPCR. CCK8 assays, EdU assays, Scratch assay and Transwell migration assay conducted to detect the role of circTENM3 in PCa cells in vitro. RIP assay, RNA-pull down and luciferase reporter assay were performed to explore the mechanism of circTENM3. Gain-of-function analysis was performed to reveal the function of circTENM3 in PCa in vivo.

Results

The results revealed that the expression level of circTENM3 was significantly down-regulated in PCa. CircTENM3 overexpression alleviated the progression of PCa in vitro. Mechanistically, circTENM3 enhanced RUNX3 levels via miR-558 sponge. Gain-of-function analysis determined that circTENM3 overexpression could inhibit PCa progression in vitro.

Conclusions

Our research offers profound insights into the protective role played by circTENM3 in PCa. CircTENM3 operates as a sponge for miR-558, thereby triggering the elevation of RUNX3 expression, which subsequently curbs the progression of PCa.
Development and validation of risk prediction nomograms for acute respiratory failure in elderly patients with hip fracture
Authors: Li Yue , Dong Bo
Published: November 2023

Background

Hip fractures in the elderly often lead to acute respiratory failure, but there is currently no tool to assess the prognosis of such patients. This study aims to develop a risk prediction model for respiratory failure in these patients.

Methods

A retrospective cross-sectional study was conducted using the Medical Information Mart for Intensive Care (MIMIC)-IV database, incorporating data from 3,266 patients with hip fractures aged over 55 years from 2008 to 2019. Data included demographic information, laboratory indicators, comorbidities, and treatment methods. Patients were divided into a training group (70%) and a validation group (30%). Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select prognostic predictors, and a visualized nomogram model was constructed using multivariate logistic regression analysis. Model performance and clinical applicability were assessed. Statistical analyses were done using R4.2.2, with P < 0.05 deemed significant.

Results

Seven key factors, including age, height, albumin, chloride, pneumonia, acute kidney injury (AKI), and heparin use, were associated with respiratory failure risk. The model demonstrated good performance with area under the curve (AUC) values of 0.77 and 0.73 in the training and validation sets, respectively. The calibration curve showed good agreement, and decision curve analysis (DCA) indicated the model's clinical benefit.

Conclusions

This risk prediction model can effectively predict respiratory failure in hip fracture patients, assisting clinicians in identifying high-risk individuals and providing evidence-based references for treatment strategies.
A novel assessment, diagnostic and treatment system for diabetic foot
Authors: Viadé Jordi , Nicolás Maria , Bundó Magdalena , Sirvent Marc , Riera Clàudia , Sabriá Miquel
Published: November 2023

Background

This report aims to present a novel system for the management of foot lesions in patients with diabetes. It was developed in the diabetic foot unit (DFU) of the Mutua de Terrassa University Hospital (HUMT) by primary care professionals, the Diabetic Foot Clinic (DFC), and during emergency cases treated by our group based on daily activities in patients with neuropathy or neuroischemia.

Body

This system considers five degrees of action based on two fixed variables: presence of infection and lesion depth. These two variables allowed the user to investigate aspects of the system until the overall action required by the pathology is made clear. These variables establish pathology stages of various severities that require different actions in aspects of care, management and treatment.

Conclusion

This tool facilitates diagnosis, treatment, and coordination among different members of a multidisciplinary team working in specialized hospital units, primary care centers, and emergency settings.
Novel variants in TUBB8 gene cause multiple phenotypic abnormalities in human oocytes and early embryos
Authors: Hu Tingwenyi , Li Chong , Qiao Sen , Liu Weiwei , Han Wei , Li Wei , Shi Rong , Xue Xia , Shi Juanzi , Huang Guoning , Lin Tingting
Published: November 2023

Background

The genotype-phenotype relationships between TUBB8 variants and female infertility are difficult to clearly define due to the complex inheritance patterns and the highly heterogeneous phenotypes. This study aims to identify novel TUBB8 variants and relevant phenotypes in more infertile females.

Methods

A total of 35 females with primary infertility were recruited from two reproductive centers and investigated for identifying variants in TUBB8. Pedigree analysis, in-silico analysis and molecular remodeling were performed to assess their clinical significance. The effects of the variants on human oocytes and embryos as well as HeLa cells were analyzed by morphological observations, immunostaining and Western blot.

Results

We totally identified five novel variants (p.G13R, p.Y50C, p.T136I, p.F265V and p.T366A) and five previously reported variants (p.I4L, p.L42V, p.Q134*, p.V255M and p.V349I) in TUBB8 from 9 unrelated females with primary infertility. These variants were rare and highly conserved among different species, and were inherited in autosomal dominant/recessive patterns, or occurred de novo. In vitro functional assays in HeLa cells revealed that exogenous expression of mutant TUBB8 proteins caused different degrees of microtubule structural disruption. The existence of these pathogenic TUBB8 variants finally induced oocyte maturation arrest or morphological abnormalities, fertilization failure, cleavage failure, embryonic development defects and implantation failure in the affected females.

Conclusion

These findings enriched the variant spectrum of TUBB8 gene and could contribute to optimize genetic counselling and clinical management of females with primary infertility.
Novel glycosyl prodrug of RXP03 as MMP-11 prodrug: design, synthesis and virtual screening
Authors: Abdou Moaz M. , Ötvös Ferenc , Dong Dewen , Matziari Magdalini
Published: November 2023

Like most phosphinic acids, the potent and selective RXP03 inhibitor of different MMPs exhibited moderate absorption and low bioavailability, which impaired its use. In an unprecedented attempt, we present an interesting synthetic approach to a new class of phosphinate prodrug, glycosyl ester of RXP03, to provide a potentially improved blood–brain barrier (BBB) behavior compared to the former lead compound RXP03. To validate this speculation, a predictive study for permeability enhancer of glycosyl ester of RXP03 showed encouraging insights to improve drug delivery across biological barriers.
Development and evaluation of specific polymerase chain reaction assays for detecting Theileria equi genotypes
Authors: Ahedor Believe , Otgonsuren Davaajav , Zhyldyz Atambekova , Guswanto Azirwan , Ngigi Noel Muthoni Mumbi , Valinotti Maria Fátima Rodríguez , Kothalawala Hemal , Kalaichelvan Nizanantha , Silva Seekkuge Susil Priyantha , Kothalawala Hemali , Acosta Tomás Javier , Sivakumar Thillaiampalam , Yokoyama Naoaki
Published: November 2023

Background

Theileria equi causes equine piroplasmosis, an economically significant disease that affects horses and other equids worldwide. Based on 18S ribosomal RNA (18S rRNA sequences), T. equi can be classified into five genotypes: A, B, C, D, and E. These genotypes have implications for disease management and control. However, no conventional polymerase chain reaction (PCR) assays are available to differentiate the genotypes of T. equi. To overcome this limitation, we developed and evaluated PCR assays specific for the detection of each T. equi genotype.

Methods

A pair of forward and reverse primers, specifically targeting the 18S rRNA sequence of each genotype, was designed. The genotype-specific PCR assays were evaluated for their specificity using plasmids containing inserts of the 18S rRNA sequence of each genotype. Subsequently, the assays were tested on 270 T. equi-positive equine blood DNA samples (92 from donkeys in Sri Lanka and 178 from horses in Paraguay). 18S rRNA sequences derived from the PCR amplicons were analyzed phylogenetically.

Results

Each genotype-specific PCR assay accurately targeted the intended genotype, and did not produce any amplicons when 18S rRNA from other T. equi genotypes or genomic DNA of Babesia caballi or uninfected horse blood was used as the template. Previous studies employing PCR sequencing methods identified T. equi genotypes C and D in the Sri Lankan samples, and genotypes A and C in the Paraguayan samples. In contrast, our PCR assay demonstrated exceptional sensitivity by detecting four genotypes (A, C, D, and E) in the Sri Lankan samples and all five genotypes in the Paraguayan samples. All the Sri Lankan samples and 93.3% of the Paraguayan samples tested positive for at least one genotype, further emphasizing the sensitivity of our assays. The PCR assays also had the ability to detect co-infections, where multiple genotypes in various combinations were detected in 90.2% and 22.5% of the Sri Lankan and Paraguayan samples, respectively. Furthermore, the sequences obtained from PCR amplicons clustered in the respective phylogenetic clades for each genotype, validating the specificity of our genotype-specific PCR assays.

Conclusions

The genotype-specific PCR assays developed in the present study are reliable tools for the differential detection of T. equi genotypes.

Graphical abstract
Cost-effectiveness of continuous glucose monitoring with FreeStyle Libre® in Brazilian insulin-treated patients with types 1 and 2 diabetes mellitus
Authors: Bahia Luciana , Mello Karla F. , Lemos Lívia Lovato Pires , Costa Naiane Lima , Mulinari Eduardo , Malerbi Domingos A.
Published: November 2023

Background

Hypoglycemia is a barrier to optimal glucose control in the treatment of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Blood glucose monitoring is essential in diabetes management. Inappropriate glucose management is associated with high mortality and morbidity. FreeStyle Libre® (FSL) is a continuous glucose monitoring (CGM) system that provides effective, safe, and convenient glucose monitoring, without routine finger pricking. This study aims to estimate the incremental cost-effectiveness ratio (ICER) of the FSL system in comparison to conventional Self-monitoring of blood glucose (SMBG) in T1DM and T2DM patients that require intensive insulin therapy.

Methods

A decision-tree model was developed to compare the cost-effectiveness ratio between FSL and conventional SMBG from the perspective of the Brazilian Public Healthcare System (SUS). The model captures the cumulative rates of acute complications such as severe hypoglicemia and diabetic ketoacidosis, per-event costs, and quality-adjusted life-years (QALYs) gained over a 1-year time horizon in adult and pediatric patients (≥ 4 years old) with T1DM or T2DM. Inputs from the Brazilian health databases, clinical trials, and real-world data were used in the study.

Results

The results demonstrated that, regarding solely severe hypoglicemia and diabetic ketoacidosis events, T1DM have a QALY difference of 0.276, a cost difference of R$ 7.255, and an ICER of R$ 26,267.69 per QALY gained for CGM with FSL, when compared to conventional SMBG. T2DM results demonstrated equally a QALY difference of 0.184, a cost difference of R$ 7290, and an ICER of R$ 39,692.67 per QALY gained, in favour of CGM with FSL.

Conclusion

Our findings demonstrated that FSL is cost-effective in T1DM and T2DM for acute diabetic complications, from a SUS perspective. CGM with FSL can promote safe, convenient, and cost-effective glucose monitoring, therefore contributing to the improvement of the incidence of complications and quality of life.
Dataset of the impact of food insecurity on health outcomes in sub-Saharan Africa
Authors: Beyene Sisay Demissew
Published: November 2023

Objectives

The 2030 Sustainable Development Goals (SDGs) have goals and targets, including food insecurity and health outcomes. Hence, information about socioeconomic variables that determine the health outcomes of people is essential for health-related research, planning, and policy development. Therefore, this data paper aims to present (describe) the dataset of eight socioeconomic variables for 31 sub-Saharan Africa (SSA) countries from 2001 to 2018.

Data descriptions

The dataset was official information obtained via open online sources from the Food and Agricultural Organization (FAO), the World Bank (WB), and the United Nations Development Programme (UNDP). It included 558 observations and eight variables, such as life expectancy (LEXP), infant mortality (INFMOR), the prevalence of undernourishment (PRUND), average dietary energy supply (AVRDES), Gross domestic product per capita (GDPPC), general government health expenditure (GOVEXP), urbanisation (URBAN), and mean years of schooling (MNSCHOOL). Moreover, all the data estimation is conducted by Statistical Software (STATA) version 15. This paper achieved its intended objective with a detailed and understandable description.
Imiquimod-induced pruritus in female wild-type and knockin Wistar rats: underscoring behavioral scratching in a rat model for antipruritic treatments
Authors: Lariosa-Willingham Karen , Leonoudakis Dmitri , Simon Florian , Walker Kendall , Guillaume Philippe , Warren Liling , Stratton Jennifer
Published: November 2023

Objectives

Animal models of skin disease are used to evaluate therapeutics to alleviate disease. One common clinical dermatological complaint is pruritus (itch), but there is a lack of standardization in the characterization of pre-clinical models and scratching behavior, a key itch endpoint, is often neglected. One such model is the widely used imiquimod (IMQ) mouse model of psoriasis. However, it lacks characterized behavioral attributes like scratching, nor has widely expanded to other species like rats.

Given these important attributes, this study was designed to broaden the characterization beyond the expected IMQ-induced psoriasis-like skin inflammatory skin changes and to validate the role of a potential therapeutic agent for pruritus in our genetic rat model. The study included female Wistar rats and genetically modified knockin (humanized proteinase-activated receptor 2 (F2RL1) female rats, with the widely used C57BL/6 J mice as a methodology control for typical IMQ dosing.

Results

We demonstrate that the IMQ model can be reproduced in rats, including their genetically modified derivatives, and how scratching can be used as a key behavioral endpoint. We systemically delivered an anti-PAR2 antibody (P24E1102) which reversed scratching bouts—validating this behavioral methodology and have shown its feasibility and value in identifying effective antipruritic drugs.
A 2-decade bibliometric analysis of epigenetics of cardiovascular disease: from past to present
Authors: Mao Yukang , Zhao Kun , Chen Nannan , Fu Qiangqiang , Zhou Yimeng , Kong Chuiyu , Li Peng , Yang Chuanxi
Published: November 2023

Background

Cardiovascular disease (CVD) remains a major health killer worldwide, and the role of epigenetic regulation in CVD has been widely studied in recent decades. Herein, we perform a bibliometric study to decipher how research topics in this field have evolved during the past 2 decades.

Results

Publications on epigenetics in CVD produced during the period 2000–2022 were retrieved from the Web of Science Core Collection (WoSCC). We utilized Bibliometrix to build a science map of the publications and applied VOSviewer and CiteSpace to assess co-authorship, co-citation, co-occurrence, and bibliographic coupling. In total, 27,762 publications were included for bibliometric analysis. The yearly amount of publications experienced exponential growth. The top 3 most influential countries were China, the United States, and Germany, while the most cited institutions were Nanjing Medical University, Harbin Medical University, and Shanghai Jiao Tong University. Four major research trends were identified: (a) epigenetic mechanisms of CVD; (b) epigenetics-based therapies for CVD; (c) epigenetic profiles of specific CVDs; and (d) epigenetic biomarkers for CVD diagnosis/prediction. The latest and most important research topics, including “nlrp3 inflammasome”, “myocardial injury”, and “reperfusion injury”, were determined by detecting citation bursts of co-occurring keywords. The most cited reference was a review of the current knowledge about how miRNAs recognize target genes and modulate their expression and function.

Conclusions

The number and impact of global publications on epigenetics in CVD have expanded rapidly over time. Our findings may provide insights into the epigenetic basis of CVD pathogenesis, diagnosis, and treatment.
Modulation of cell cycle increases CRISPR-mediated homology-directed DNA repair
Authors: Li Guoling , Yang Xiaohui , Luo Xinxin , Wu Zhenfang , Yang Huaqiang
Published: November 2023

Background

Gene knock‐in (KI) in animal cells via homology‐directed repair (HDR) is an inefficient process, requiring a laborious work for screening from few modified cells. HDR tends to occur in the S and G2/M phases of cell cycle; therefore, strategies that enhance the proportion of cells in these specific phases could improve HDR efficiency.

Results

We used various types of cell cycle inhibitors to synchronize the cell cycle in S and G2/M phases in order to investigate their effect on regulating CRISPR/Cas9-mediated HDR. Our results indicated that the four small molecules—docetaxel, irinotecan, nocodazole and mitomycin C—promoted CRISPR/Cas9-mediated KI with different homologous donor types in various animal cells. Moreover, the small molecule inhibitors enhanced KI in animal embryos. Molecular analysis identified common signal pathways activated during crosstalk between cell cycle and DNA repair. Synchronization of the cell cycle in the S and G2/M phases results in CDK1/CCNB1 protein accumulation, which can initiate the HDR process by activating HDR factors to facilitate effective end resection of CRISPR-cleaved double-strand breaks. We have demonstrated that augmenting protein levels of factors associated with the cell cycle via overexpression can facilitate KI in animal cells, consistent with the effect of small molecules.

Conclusion

Small molecules that induce cell cycle synchronization in S and G2/M phases promote CRISPR/Cas9-mediated HDR efficiency in animal cells and embryos. Our research reveals the common molecular mechanisms that bridge cell cycle progression and HDR activity, which will inform further work to use HDR as an effective tool for preparing genetically modified animals or for gene therapy.
Design and analysis of wireless data center network topology HCDCN based on VLC
Authors: Zhang Qingfang , Du Xiaoyu , Li Jie , Han Zhijie
Published: November 2023

With the rapid development of the Internet of Things, big data, cloud computing and other industries, the data center network, as the core infrastructure of the computing industry, is becoming increasingly important. Wireless communication technology is developing rapidly. This paper uses visible light wireless communication technology to build a wireless data center network, solving the problems of complex wiring and expansion difficulties in the existing data center network.

Aiming at the problems of insufficient spectrum, low bandwidth utilization and large energy consumption in the existing wireless data center, this paper adopts the visible light wireless communication technology based on LED, and proposes a new wireless data center network structure HCDCN. Firstly, work have been done to analyze the feasibility of introducing data centers in this technology, and transform server racks in combination with the characteristics of the technology. Secondly, the construction process of the structure is introduced and a new coding rule is proposed. In order to increase the routing efficiency and fault tolerance, the rack top link routing path is added, and an efficient routing algorithm is designed. Finally, the aggregate throughput of HCDCN under different scales is obtained through experiments, and the network performance of HCDCN structure is compared with that of OWCells and Mesh structure. Experiments have proved that HCDCN's network performance is better than the other two structures under the same conditions. The new wireless data center network proposed in this paper has largely alleviated the bandwidth shortage of hotspot servers.
A case–control comparison of acute-phase peripheral blood gene expression in participants diagnosed with minor ischaemic stroke or stroke mimics
Authors: Moxon Joseph V. , Calcino Andrew , Kraeuter Ann-Katrin , Phie James , Anderson Georgina , Standley Glenys , Sealey Cindy , Jones Rhondda E. , Field Matt A. , Golledge Jonathan
Published: November 2023

Background

Past studies suggest that there are changes in peripheral blood cell gene expression in response to ischaemic stroke; however, the specific changes which occur during the acute phase are poorly characterised. The current study aimed to identify peripheral blood cell genes specifically associated with the early response to ischaemic stroke using whole blood samples collected from participants diagnosed with ischaemic stroke (n = 29) or stroke mimics (n = 27) following emergency presentation to hospital. Long non-coding RNA (lncRNA), mRNA and micro-RNA (miRNA) abundance was measured by RNA-seq, and the consensusDE package was used to identify genes which were differentially expressed between groups. A sensitivity analysis excluding two participants with metastatic disease was also conducted.

Results

The mean time from symptom onset to blood collection was 2.6 h. Most strokes were mild (median NIH stroke scale score 2.0). Ten mRNAs (all down-regulated in samples provided by patients experiencing ischaemic stroke) and 30 miRNAs (14 over-expressed and 16 under-expressed in participants with ischaemic stroke) were significantly different between groups in the whole cohort and sensitivity analyses. No significant over-representation of gene ontology categories by the differentially expressed genes was observed. Random forest analysis suggested a panel of differentially expressed genes (ADGRG7 and miRNAs 96, 532, 6766, 6798 and 6804) as potential ischaemic stroke biomarkers, although modelling analyses demonstrated that these genes had poor diagnostic performance.

Conclusions

This study provides evidence suggesting that the early response to minor ischaemic stroke is predominantly reflected by changes in the expression of miRNAs in peripheral blood cells. Further work in independent cohorts particularly in patients with more severe stroke is needed to validate these findings and investigate their clinical relevance.