bluuebunny/crossref_metadata_2025 huggingface dataset:
Summary Report of the Arthritis Foundation and the American Orthopaedic Foot & Ankle Society’s Symposium on Targets for Osteoarthritis Research: Part 2: Treatment Options
Authors: Kim Jason S. , Amendola Annunziato , Barg Alexej , Baumhauer Judith , Brodsky James W. , Cushman Daniel M. , Gonzalez Tyler A. , Janisse Dennis , Jurynec Michael J. , Lawrence Marsh J. , Sofka Carolyn M. , Clanton Thomas O. , Anderson Donald D.
Published: October 2022

This second of a 2-part series of articles recounts the key points presented in a collaborative symposium sponsored jointly by the Arthritis Foundation and the American Orthopaedic Foot & Ankle Society with the intent to survey current treatment options for osteoarthritis (OA) of the foot and ankle. A meeting was held virtually on December 10, 2021. A group of experts were invited to present brief synopses of the current state of knowledge and research in this area. Topics were chosen by meeting organizers, who then identified and invited the expert speakers. Part 2 overviews the current treatment options, including orthotics, non–joint destructive procedures, as well as arthroscopies and arthroplasties in ankles and feet. Opportunities for future research are also discussed, such as developments in surgical options for ankle and the first metatarsophalangeal joint. The OA scientific community, including funding agencies, academia, industry, and regulatory agencies, must recognize the importance to patients of addressing the foot and ankle with improved basic, translational, and clinical research.

Level of Evidence:

Level V, review article/expert opinion.
Numerical Simulation and Experimental Verification of Laser Multi-Section Welding
Authors: Liu Jia , Jiang Tao , Shi Yan , Zhu Hongyin , Dai Yuchi
Published: October 2022

To address the problems of large welding deformation and splashing in the resistance spot welding of the lubricating oil cooler plate, the laser spot welding was employed, instead of the resistance spot welding, and a novel laser spot welding was proposed, i.e., laser multi-section welding. The major processes involved in this study referred to a finite element model of pulsed laser lap welding built by adopting SYSWELD simulation software, as well as the laser welding of various welding methods. The effect of different welding methods on the welding quality was studied, the parameters of the average power and the duty cycle were optimized in line with the comparative analysis of the experimentally achieved results and the numerical simulation. As indicated from the experimentally achieved results, when the new 6-sections welding method was adopted, the resulting welded joint achieved the most uniform heat input and the largest welding fusion area, and the tensile properties exhibited by the welded joints were significantly enhanced, whereas some pores remained. By altering the duty cycle, pores could be eliminated to further improve the quality of the joint. The mentioned process method could tackle down the problems facing conventional resistance spot welding. Furthermore, it was capable of improving the uneven heat input of the laser spot welding.
Efficacy and safety of robotic spine surgery: systematic review and meta-analysis
Authors: Luengo-Matos Setefilla , Sánchez-Gómez Luis María , Hijas-Gómez Ana Isabel , García-Carpintero Esther Elena , Ballesteros-Massó Rafael , Polo-deSantos Mar
Published: October 2022

Background

Robotic surgery (RS) may offer benefits compared with freehand/conventional surgery (FS) in the treatment of patients with spinal disease. The aim of this study was to evaluate the efficacy and safety of RS versus FS in spinal fusion.

Methods

A systematic review and meta-analysis was performed. Data analysis and risk of bias assessment were analysed using REVMAN V5.3.

Results

We found 11 randomised clinical trials involving 817 patients (FS: 408, RS: 409). The main diagnosis was degenerative spine disease. SpineAssist, Renaissance (Mazor Robotics), Tianji Robot and TiRobot robots (TINAVI Medical Technologies) were used. Pedicle screw placement within the safety zone (grades A + B according to the Gertzbein and Robbins scale) ranged from 93% to 100% in FS versus 85–100% in RS (relative risk 1.01, 95% CI  1.00–1.03, p = 0.14). Regarding intervention time, the meta-analysis showed a mean difference (MD) of 6.45 min (95% CI  −13.59 to 26.49, p = 0.53). Mean hospital stay was MD of −0.36 days (95% CI  −1.03 to 0.31, p = 0.30) with no differences between groups. Contradictory results were found regarding fluoroscopy time, although there seems to be a lower radiation dose in RS versus FS (p < 0.05). Regarding safety, the studies included surgical revision frequency.

Conclusions

No conclusive results were found suggesting that there are benefits in using RS over FS for spinal fusion. Further research with adequate patient selection, robot type and quality-of-life variables is needed.

Level of evidence: level 1.
Quality Improvement of GaN Epi-layers Grown with a Strain-Releasing Scheme on Suspended Ultrathin Si Nanofilm Substrate
Authors: Wang Kejia , Song Yuzi , Zhang Yichun , Zhang Yunyan , Cheng Zhiyuan
Published: October 2022

The material quality of III-nitrides is severely limited by the lack of cost-effective substrates with suitable lattice and thermal expansion coefficients. A suspended ultrathin silicon membrane substrate ($$\sim$$
∼
16 nm), fabricated by an easy process on SOI substrates, is thus designed for nitride epitaxial growth, which can effectively release the strain in the epi-layers, and has demonstrated large-area (Al)GaN growth with a smooth surface and greatly reduced defect density. This research provides a promising CMOS-compatible method for growing cost-effectively high-quality III-nitrides that can be used for the development of high-performance devices.
Mapping of Candidate Genes in Response to Low Nitrogen in Rice Seedlings
Authors: Li Jia , Xin Wei , Wang Weiping , Zhao Shijiao , Xu Lu , Jiang Xingdong , Duan Yuxuan , Zheng Hongliang , Yang Luomiao , Liu Hualong , Jia Yan , Zou Detang , Wang Jingguo
Published: October 2022

Nitrogen is not only a macronutrient essential for crop growth and development, but also one of the most critical nutrients in farmland ecosystem. Insufficient nitrogen supply will lead to crop yield reduction, while excessive application of nitrogen fertilizer will cause agricultural and eco-environment damage. Therefore, mining low-nitrogen tolerant rice genes and improving nitrogen use efficiency are of great significance to the sustainable development of agriculture. This study was conducted by Genome-wide association study on a basis of two root morphological traits (root length and root diameter) and 788,396 SNPs of a natural population of 295 rice varieties. The transcriptome of low-nitrogen tolerant variety (Longjing 31) and low-nitrogen sensitive variety (Songjing 10) were sequenced between low and high nitrogen treatments. A total of 35 QTLs containing 493 genes were mapped. 3085 differential expressed genes were identified. Among these 493 genes, 174 genes showed different haplotype patterns. There were significant phenotype differences among different haplotypes of 58 genes with haplotype differences. These 58 genes were hypothesized as candidate genes for low nitrogen tolerance related to root morphology. Finally, six genes (Os07g0471300, Os11g0230400, Os11g0229300, Os11g0229400, Os11g0618300 and Os11g0229333) which expressed differentially in Longjing 31 were defined as more valuable candidate genes for low-nitrogen tolerance. The results revealed the response characteristics of rice to low-nitrogen, and provided insights into regulatory mechanisms of rice to nitrogen deficiency.
New insights into the genetic resistance to paratuberculosis in Holstein cattle via single-step genomic evaluation
Authors: Sanchez Marie-Pierre , Tribout Thierry , Fritz Sébastien , Guatteo Raphaël , Fourichon Christine , Schibler Laurent , Delafosse Arnaud , Boichard Didier
Published: October 2022

Background

Bovine paratuberculosis, or Johne’s disease (JD), is a contagious and incurable disease caused byMycobacterium aviumsubsp.paratuberculosis(MAP). It has adverse effects on animal welfare and is very difficult to control, leading to serious economic consequences. An important line of defense to this disease is host genetic resistance to MAP, which, when it will be more fully understood, could be improved through selective breeding. Using a large dataset of Holstein cows (161,253 animals including 56,766 cows with ELISA serological phenotypes and 12,431 animals with genotypes), we applied a single-step single nucleotide polymorphism (SNP) best linear unbiased prediction approach to investigate the genetic determinism underlying resistance to this disease (heritability estimate and identification of relevant genomic regions) and estimated genetic trends, reliability, and relative risk factors associated with genomic predictions.

Results

Resistance to JD was moderately heritable (0.14) and 16 genomic regions were detected that accounted for at least 0.05% of the breeding values variance (GV) in resistance to JD, and were located on chromosomes 1, 3, 5, 6, 7, 19, 20, 21, 23, 25, and 27, with the highest percentage of variance explained by regions on chromosomes 23 (0.36% GV), 5 (0.22% GV), 1 (0.14% GV), and 3 (0.13% GV). When estimated for the whole chromosomes, the autosomes with the largest overall contributions were chromosomes 3 (5.3% GV), 10 (4.8%), 23 (4.7%), 1 (3.6%), 7 (3.4%), 5 (2.9%), 12 (2.5%), 11 (2.2%), and 13 (2%). We estimated a slightly favorable genetic trend in resistance to JD over the last two decades, which can be explained by a low positive genetic correlation between resistance to JD and total merit index (+ 0.06). Finally, in a validation population of 907 cows, relatively reliable genomic predictions (reliability = 0.55) were obtained, which allowed the identification of cows at high risk of infection.

Conclusions

This study provides new insights into the genetic determinism of resistance to JD and shows that this trait can be predicted from SNP genotypes. It has led to the implementation of a single-step genomic evaluation that should rapidly become an effective tool for controlling paratuberculosis on French Holstein farms.
Comparison of the effect of melatonin, dexmedetomidine, and gabapentin on reduction of postoperative pain and anxiety following laminectomy: a randomized clinical trial
Authors: Jouybar Reza , Kazemifar Somayeh , Asmarian Naeimehossadat , Karami Ali , Khademi Saeed
Published: October 2022

Background

This study aimed to compare the effects of melatonin, dexmedetomidine, and gabapentin on postoperative pain and anxiety following laminectomy.

Methods

In this randomized clinical trial, 99 patients aged 40–60 years old with American Society of Anesthesiologists physical status I-II undergoing laminectomy were divided into three groups receiving 600mg gabapentin (group G), 10mg melatonin (group M), or starch tablets (group D). The Hospital Anxiety and Depression Scale (HADS) was used to measure postoperative anxiety while a Visual Analogue Scale (VAS) was employed to measure pain severity. Patients’ satisfaction with pain treatment was also measured together with the frequency of nausea and vomiting.

Results

The postoperative HADS decreased in all groups over time. Time and group had no significant interaction effect on the HADS score. Patients in the melatonin group had lower HADS at 2 and 6h after surgery. According to the VAS, the groups significantly differed in pain scores 6 and 24h after surgery. Lower VAS scores were observed 6h after surgery in the dexmedetomidine group compared with the gabapentin group and 24h after surgery in the dexmedetomidine group compared with the gabapentin and melatonin groups. Narcotic requirements, patients’ satisfaction, and vital sign changes did not significantly vary among the groups. Notably, patients in the melatonin group had less nausea and vomiting.

Trial registration:

This study was registered in the Iranian Registry of Clinical Trials (No. IRCT20141009019470N82, 29.06.2019) where the trial protocol could be accessed.

Conclusion

Melatonin is effective as a postoperative anti-anxiety drug. Dexmedetomidine is useful in reducing postoperative pain.
Evaluation of the safety and efficacy of a novel Anatomical classification and dUal anchoRing theory to Optimize the tavR strategy for pure severe Aortic regurgitation (AURORA): a prospective cohort study
Authors: Yao Jing , Lu Zhi-Nan , Modine Thomas , Jilaihawi Hasan , Piazza Nicolo , Tang Yi-Da , Xu Ji-Zhe , Peng Xiao-Ping , Wang Hai-Ping , Li Chuan-Bao , Chen Hui , Liu Chang-Fu , Jiang Zheng-Ming , Li Jie , Yu Fei-Cheng , Han Ke , Wang Sheng , Huang Hui , Song Guang-Yuan
Published: October 2022

Background

Success rate of transcatheter aortic valve replacement (TAVR) in aortic regurgitation (AR) patients is relatively low on account of the absence of calcified anchoring structures. Morphological classification and corresponding TAVR strategies for AR are lacking yet.

Methods

The AURORA study is a prospective, multicenter, single-arm cohort study to evaluate the safety and efficacy of transfemoral TAVR for severe AR in patients with high or prohibitive risk for surgery. Patients who are ≥ 65 years and diagnosed with severe pure AR as defined by the Echocardiographic Core Laboratory will be consecutively enrolled for further multidetector computed tomography (MDCT) scanning and multiplanar analyses. Based on a new anatomical classification and dual anchoring theory, patients will be classified into 4 types according to the level of the anchoring area. Types 1, 2 and 3 (at least 2 anchoring areas) will undergo the TAVR procedure with a domestic Chinese self-expanding valve (VitaFlow Valve, MicroPort, Shanghai, China), whereas type 4 (0 or 1 anchoring area) patients will be considered unsuitable for TAVR and will receive medical treatment. Our goal is to recruit 100 patients to account for 10% missing data or loss of patients to follow-up. Procedural, 30-day, 6-month and 12-month outcomes will be assessed according to Valve Academic Research Consortium-3 criteria.

Discussion

The AURORA study will establish a new AR anatomical classification based on dual anchoring theory through MDCT multiplanar measurement and assess the safety and efficacy of TAVR guided by this new classification and strategy in AR patients.

Trial registration: This Study was registered at Chinses Clinical Trial Registry. The registration number: ChiCTR2200055415; The date of registration: 9, January 2022; The URL of the registration: http://www.chictr.org.cn/showproj.aspx?proj=141209.
The use of frozen embryos and frozen sperm have complementary IVF outcomes: a retrospective analysis in couples experiencing IVF/Donor and IVF/Husband
Authors: Zhu Yong , Zhang Feng , Chen Hua , Sun Xiaoxi , Jiang Feng
Published: October 2022

Background

The cryopreservation of sperm or embryos has been an important strategy in the treatment of infertility. Recently studies have revealed the outcomes after IVF (in vitro fertilization) treatment for single-factor exposure either to frozen sperm or embryos.

Methods

This retrospective study was to uncover the exposure to both frozen sperm and embryo effects using IVF/H (in vitro fertilization using husbands’ fresh sperm) or IVF/D (in vitro fertilization using donors’ frozen sperm) treatment.

Results

The results showed the clinical pregnancy rate (CPR), live birth rate (LBR) and low birth weight rate (LBW) increased to 63.2% (or 68.1%), 61.1% (or 66.4%) and 15.8% (or 16.2%) after using frozen embryo transfer within Group IVF/H (or Group IVF/D). After using frozen sperm, the high-quality embryo rate (HER) increased to 52% and baby with birth defect rate (BDR) reduced to 0% in subgroup D/ET comparing to subgroup H/ET. While the fertilization rate (FER), cleavage rate (CLR), HER and multiple pregnancy rate (MUR) reduced to 75%, 71%, 45% and 9.2% in subgroup D/FET comparing to subgroup H/FET. Finally, our study found accumulative frozen gamete effects, including both sperm and embryos, led to the significantly increasing in the HER (p < 0.05), CPR (p < 0.001), LBR (p < 0.001) and LBW (p < 0.05) in subgroup D/FET comparing to subgroup H/ET.

Conclusion

The use of frozen embryos and frozen sperm have complementary IVF outcomes. Our findings highlighted the parent’s distinguished frozen effect not only for clinical studies but also for basic research on the mechanism of cellular response adaptations to cryopreservation.
A comprehensive analysis of penile cancer in the region with the highest worldwide incidence reveals new insights into the disease
Authors: Teixeira Júnior Antonio Augusto Lima , da Costa Melo Syomara Pereira , Pinho Jaqueline Diniz , Sobrinho Thaís Bastos Moraes , Rocha Thalita Moura Silva , Duarte Denner Rodrigo Diniz , de Oliveira Barbosa Liseana , Duarte Wesliany Everton , de Castro Belfort Marta Regina , Duarte Kelly Gomes , da Silva Neto Antonio Lima , de Ribamar Rodrigues Calixto José , Paiva Paiva Lúcio Cristiano , do Nascimento Francisco Sérgio Moura Silva , Alencar Junior Antonio Machado , Khayat André Salim , da Graça Carvalhal Frazão Corrêa Rita , Lages Joyce Santos , dos Reis Rodolfo Borges , Araújo Wilson Silva , Silva Gyl Eanes Barros
Published: October 2022

Background

Although penile cancer (PC) is uncommon in developed countries, it is widespread in developing countries. The state of Maranhão (Northeast, Brazil) has the highest global incidence recorded for PC, and, despite its socioeconomic vulnerability, it has been attributed to human papillomavirus (HPV) infection. This study aimed to determine the histopathological features, the prevalence of HPV infection, and the immunohistochemical profile of PC in Maranhão.

Methods

A retrospective cohort of 200 PC cases were evaluated. HPV detection was performed using nested-PCR followed by direct sequencing for genotyping. Immunohistochemistry (IHC) was performed using monoclonal antibodies anti-p16INK4a, p53, and ki-67.

Results

Our data revealed a delay of 17 months in diagnosis, a high rate of penile amputation (96.5%), and HPV infection (80.5%) in patients from Maranhão (Molecular detection). We demonstrated the high rate of HPV in PC also by histopathological and IHC analysis. Most patients presented koilocytosis (75.5%), which was associated with those reporting more than 10 different sexual partners during their lifetime (p = 0.001). IHC revealed frequent p16INK4a overexpression (26.0%) associated with basaloid (p < 0.001) and high-grade tumors (p = 0.008). Interestingly, p16 appears not to be a better prognostic factor in our disease-free survival analysis, as previously reported. We also demonstrated high ki-67 and p53 expression in a subset of cases, which was related to worse prognostic factors such as high-grade tumors, angiolymphatic and perineural invasion, and lymph node metastasis. We found a significant impact of high ki-67 (p = 0.002, log-rank) and p53 (p = 0.032, log-rank) expression on decreasing patients’ survival, as well as grade, pT, stage, pattern, and depth of invasion (p < 0.05, log-rank).

Conclusions

Our data reaffirmed the high incidence of HPV infection in PC cases from Maranhão and offer new insights into potential factors that may contribute to the high PC incidence in the region. We highlighted the possible association of HPV with worse clinical prognosis factors, differently from what was observed in other regions. Furthermore, our IHC analysis reinforces p16, ki-67, and p53 expression as important diagnosis and/or prognosis biomarkers, potentially used in the clinical setting in emerging countries such as Brazil.
Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines
Authors: Koronkiewicz Mirosława , Kazimierczuk Zygmunt , Orzeszko Andrzej
Published: October 2022

Background

The protein kinases CK2 and PIM-1 are involved in cell proliferation and survival, the cell cycle, and drug resistance, and they are found overexpressed in virtually all types of human cancer, including breast cancer. In this study, we investigated the antitumor activity of a deoxynucleoside derivative, the protein kinase inhibitor compound 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazole (K164, also termed TDB), inter alia CK2 and PIM-1, on breast cancer cell lines (MDA-MB-231, MCF-7, and SK-BR-3).

Methods

An evaluation of the cytotoxic and proapoptotic effects, mitochondrial membrane potential (ΔΨm), and cell cycle progression was performed using an MTT assay, flow cytometry, and microscopic analysis. The Western blotting method was used to analyze the level of proteins important for the survival of breast cancer cells and proteins phosphorylated by the CK2 and PIM-1 kinases.

Results

The examined compound demonstrated the inhibition of cell viability in all the tested cell lines and apoptotic activity, especially in the MCF-7 and SK-BR-3 cells. Changes in the mitochondrial membrane potential (ΔΨm), cell cycle progression, and the level of the proteins studied were also observed.

Conclusions

The investigated CK2 and PIM-1 kinase inhibitor K164 is a promising compound that can be considered a potential agent in targeted therapy in selected types of breast cancer; therefore, further research is necessary.
Effects of let-7a microRNA and C–C chemokine receptor type 7 expression on cellular function and prognosis in esophageal squamous cell carcinoma
Authors: Yura Masahiro , Fukuda Kazumasa , Matsuda Satoru , Irino Tomoyuki , Nakamura Rieko , Kawakubo Hirofumi , Takeuchi Hiroya , Kitagawa Yuko
Published: October 2022

Background

C–C chemokine receptor type 7 (CCR7) participates in chemotactic and metastatic responses in various cancers, including in esophageal squamous cell carcinoma (ESCC). The microRNA (miRNA) let-7a suppresses migration and invasion of various types of cancer cells by downregulating CCR7 expression.

Methods

The expression levels of CCR7 and let-7a were measured in the cell lines, tumor, and peritumoral tissues of ESCC patients. KYSE cell lines were transfected with synthetic let-7a miRNA and a let-7a miRNA inhibitor, and their CCR7 expression levels as well as invasive ability were evaluated. A highly invasive cell line was established via an invasion assay, and CCR7 expression level along with let-7a level was subsequently evaluated. Cancer cells overexpressing CCR7 were injected subcutaneously into mice, and the animals were monitored for tumor growth along with lymph node metastasis.

Results

A negative correlation between CCR7 and let-7a expression was observed in the ESCC cell lines as well as in tissue samples from patients. Synthetic let-7a decreased CCR7 expression level, while the let-7a inhibitor increased it. In vitro, the established highly invasive cancer cells with high and low levels of CCR7 and let-7a expression, respectively, exhibited a greater invasive ability than the wild-type cell line. The cells were associated with tumor growth and lymph node metastasis in mice. Patients in the high-CCR7/low-let-7a group had the worst prognosis, with a five-year recurrence free survival (5-RFS) rate of 37.5%, followed by the high-CCR7/high-let-7a (5-RFS: 60.0%) and low-CCR7 (5-RFS: 85.7%; p = 0.038) groups.

Conclusions

The expression of CCR7 was downregulated by let-7a miRNA in esophageal cancer cells. The decrease in let-7a expression level led to the increased expression level of CCR7 in ESCC cells, consequently increasing their invasive ability and malignancy and resulting in a worse prognosis for ESCC patients.

Trial registration.

Retrospectively registered.
Hoarding symptoms are associated with higher rates of disability than other medical and psychiatric disorders across multiple domains of functioning
Authors: Nutley Sara K. , Read Michael , Martinez Stephanie , Eichenbaum Joseph , Nosheny Rachel L. , Weiner Michael , Mackin R. Scott , Mathews Carol A.
Published: October 2022

Background

Hoarding symptoms are associated with functional impairment, though investigation of disability among individuals with hoarding disorder has largely focused on clutter-related impairment to home management activities and difficulties using space because of clutter. This analysis assesses disability among individuals with hoarding symptoms in multiple domains of everyday functioning, including cognition, mobility, self-care, interpersonal and community-level interactions, and home management. The magnitude of the association between hoarding and disability was compared to that of medical and psychiatric disorders with documented high disability burden, including major depressive disorder (MDD), diabetes, and chronic pain.

Methods

Data were cross-sectionally collected from 16,312 adult participants enrolled in an internet-based research registry, the Brain Health Registry. Pearson’s chi-square tests and multivariable logistic regression models were used to quantify the relationship between hoarding and functional ability relative to MDD, diabetes, and chronic pain.

Results

More than one in ten participants endorsed clinical (5.7%) or subclinical (5.7%) hoarding symptoms (CHS and SCHS, respectively). After adjusting for participant demographic characteristics and psychiatric and medical comorbidity, CHS and SCHS were associated with increased odds of impairment in all domains of functioning. Moderate to extreme impairment was endorsed more frequently by those with CHS or SCHS compared to those with self-reported MDD, diabetes, and/or chronic pain in nearly all domains (e.g., difficulty with day-to-day work or school: CHS: 18.7% vs. MDD: 11.8%, p < 0.0001) except mobility and self-care. While those with current depressive symptoms endorsed higher rates of impairment than those with hoarding symptoms, disability was most prevalent among those endorsing both hoarding and comorbid depressive symptoms.

Conclusions

Hoarding symptoms are associated with profound disability in all domains of functioning. The burden of hoarding is comparable to that of other medical and psychiatric illnesses with known high rates of functional impairment. Future studies should examine the directionality and underlying causality of the observed associations, and possibly identify target interventions to minimize impairment associated with hoarding symptomatology.
Awareness and willingness to accept syphilis chemoprophylaxis among men who have sex with men from three cities in China: a cross-sectional study
Authors: Zhang Xu , Qi Shu-Zhen , Du Fang-Zhi , Zheng Zhi-Ju , Cao Ning-Xiao , Zheng Xiao-Li , Zhang Rui-Li , Wang Qian-Qiu
Published: October 2022

Background

The awareness and willingness to use doxycycline-based syphilis chemoprophylaxis among men who have sex with men (MSM) in China remain largely unknown.

Methods

We recruited MSM online from Nanjing, Wuhan and Changsha between August and October of 2021, collected data from online survey, analyzed their data using descriptive statistics, and constructed binary logistic regression for factors associated with awareness and willingness to use chemoprophylaxis for syphilis and HIV.

Results

Of 725 participants (44.0% of which resided in Nanjing, 37.7% in Changsha, and 18.3% in Wuhan), a majority were under 25 years of age; 62.2% had college degrees; 11.3% were HIV positive; and 5.10% had prior syphilis infection. Only 28.83% of participants had heard of syphilis chemoprophylaxis before. Odds of knowing syphilis chemoprophylaxis were higher in those who think it is necessary to have syphilis chemoprophylaxis versus those who think it is unnecessary (P = 0.002), and were higher in those whose acquaintance had chemoprophylaxis experience before (P < 0.001). Meanwhile, those who had no previous doxycycline using history, or had positive attitude were more likely to be willing to accept syphilis chemoprophylaxis (P = 0.009, P < 0.001). Over two-thirds (67.8%) of participants preferred the PEP mode in syphilis chemoprophylaxis, and side-effects of drugs remains their most worrying aspect.

Conclusions

We observed elevated interest in syphilis chemoprophylaxis in MSM in our investigational areas, indicating that the combination of HIV and syphilis chemoprophylaxis in China is promising.
Impact of cage position on biomechanical performance of stand-alone lateral lumbar interbody fusion: a finite element analysis
Authors: Nan Chong , Ma Zhanbei , Liu Yuxiu , Ma Liang , Li Jiaqi , Zhang Wei
Published: October 2022

Background

This study aimed to compare the biomechanical performance of various cage positions in stand-alone lateral lumbar interbody fusion(SA LLIF).

Methods

An intact finite element model of the L3-L5 was reconstructed. The model was verified and analyzed. Through changing the position of the cage, SA LLIF was established in four directions: anterior placement(AP), middle placement(MP), posterior placement(PP), oblique placement(OP). A 400 N vertical axial pre-load was imposed on the superior surface of L3 and a 10 N/m moment was applied on the L3 superior surface along the radial direction to simulate movements of flexion, extension, lateral bending, and axial rotation. Various biomechanical parameters were evaluated for intact and implanted models in all loading conditions, including the range of motion (ROM) and maximum stress.

Results

In the SA LLIF models, the ROM of L4-5 was reduced by 84.21–89.03% in flexion, 72.64–82.26% in extension, 92.5-95.85% in right and left lateral bending, and 87.22–92.77% in right and left axial rotation, respectively. Meanwhile, ROM of L3-4 was mildly increased by an average of 9.6% in all motion directions. Almost all stress peaks were increased after SA LLIF, including adjacent disc, facet joints, and endplates. MP had lower stress peaks of cage and endplates in most motion modes. In terms of the stress on facet joints and disc of the cephalad segment, MP had the smallest increment.

Conclusion

In our study, SA LLIF risked accelerating the adjacent segment degeneration. The cage position had an influence on the distribution of endplate stress and the magnitude of facet joint stress. Compared with other positions, MP had the slightest effect on the stress in the adjacent facet joints. Meanwhile, MP seems to play an important role in reducing the risk of cage subsidence.
Identification of castration-dependent and -independent driver genes and pathways in castration-resistant prostate cancer (CRPC)
Authors: Li Yan , Shi Hui , Zhao Zhenjun , Xu Minghui
Published: October 2022

Background

Prostate cancer (PCa) is one of the most diagnosed cancers in the world. PCa inevitably progresses to castration-resistant prostate cancer (CRPC) after androgen deprivation therapy treatment, and castration-resistant state means a shorter survival time than other causes. Here we aimed to define castration-dependent and -independent diver genes and molecular pathways in CRPC which are responsible for such lethal metastatic events.

Methods

By employing digital gene expression (DGE) profiling, the alterations of the epididymal gene expression profile in the mature and bilateral castrated rat were explored. Then we detect and characterize the castration-dependent and -independent genes and pathways with two data set of CPRC-associated gene expression profiles publicly available on the NCBI.

Results

We identified 1,632 up-regulated and 816 down-regulated genes in rat’s epididymis after bilateral castration. Differential expression analysis of CRPC samples compared with the primary PCa samples was also done. In contrast to castration, we identified 97 up-regulated genes and 128 down-regulated genes that changed in both GEO dataset and DGE profile, and 120 up-regulated genes and 136 down-regulated genes changed only in CRPC, considered as CRPC-specific genes independent of castration. CRPC-specific DEGs were mainly enriched in cell proliferation, while CRPC-castration genes were associated with prostate gland development. NUSAP1 and NCAPG were identified as key genes, which might be promising biomarkers of the diagnosis and prognosis of CRPC.

Conclusion

Our study will provide insights into gene regulation of CRPC dependent or independent of castration and will improve understandings of CRPC development and progression.
Unintended medication discrepancies and associated factors upon patient admission to the internal medicine wards: identified through medication reconciliation
Authors: Moges Tilaye Arega , Akalu Temesgen Yihunie , Sema Faisel Dula
Published: October 2022

Background

Medication reconciliation (MedRec) is a widely accepted tool for the identification and resolution of unintended medication discrepancies (UMD).

Objective

This study aimed at assessing the magnitude and associated factors of UMD identified through medication reconciliation upon patient admission to the internal medicine wards.

Methods

Prospective cross-sectional study was conducted at the internal medicine wards of Felege Hiwot and Tibebe Ghion comprehensive specialized hospitals in Bahir Dar city, Northwest Ethiopia, from May 01 to July 30, 2021. Data were collected by using a data abstraction format prepared based on standard MedRec tools and previous studies on medication discrepancy. Pharmacists-led MedRec was made by following the WHO High5s “retroactive medication reconciliation model”. SPSS® (IBM Corporation) version 25.0 was used to analyze the data with descriptive and inferential statistics. A binary logistic regression analysis was used to identify factors associated with UMD. A statistical significance was declared at a p-value < 0.05.

Results

Among 635 adult patients, 248 (39.1%) of them had at least one UMD. The most frequent types of UMDs were omission (41.75%) and wrong dose (21.9%). The majority (75.3%) of pharmacists’ interventions were accepted. Polypharmacy at admission (p-value < 0.001), age ≥ 65 (p-value = 0.001), a unit increase on the number of comorbidities (p-value = 0.008) and information sources used for MedRec (p-value < 0.001), and medium (p-value = 0.019) and low adherence (p-value < 0.001) were significantly associated with UMD.

Conclusion

The magnitude of UMD upon patient admission to the internal medicine wards was considerably high. Omission and the wrong dose of medication were common. Older age, polypharmacy, low and medium adherence, and an increase in the number of comorbidities and information sources used for MedRec are significantly associated with UMDs. Pharmacists' interventions were mostly acceptable. Thus, the implementation of pharmacists-led MedRec in the two hospitals is indispensable for patient safety.
Characterization of data-driven clusters in diabetes-free adults and their utility for risk stratification of type 2 diabetes
Authors: Yacamán Méndez Diego , Zhou Minhao , Trolle Lagerros Ylva , Gómez Velasco Donaji V. , Tynelius Per , Gudjonsdottir Hrafnhildur , Ponce de Leon Antonio , Eeg-Olofsson Katarina , Östenson Claes-Göran , Brynedal Boel , Aguilar Salinas Carlos A. , Ebbevi David , Lager Anton
Published: October 2022

Background

The prevention of type 2 diabetes is challenging due to the variable effects of risk factors at an individual level. Data-driven methods could be useful to detect more homogeneous groups based on risk factor variability. The aim of this study was to derive characteristic phenotypes using cluster analysis of common risk factors and to assess their utility to stratify the risk of type 2 diabetes.

Methods

Data on 7317 diabetes-free adults from Sweden were used in the main analysis and on 2332 diabetes-free adults from Mexico for external validation. Clusters were based on sex, family history of diabetes, educational attainment, fasting blood glucose and insulin levels, estimated insulin resistance and β-cell function, systolic and diastolic blood pressure, and BMI. The risk of type 2 diabetes was assessed using Cox proportional hazards models. The predictive accuracy and long-term stability of the clusters were then compared to different definitions of prediabetes.

Results

Six risk phenotypes were identified independently in both cohorts: very low-risk (VLR), low-risk low β-cell function (LRLB), low-risk high β-cell function (LRHB), high-risk high blood pressure (HRHBP), high-risk β-cell failure (HRBF), and high-risk insulin-resistant (HRIR). Compared to the LRHB cluster, the VLR and LRLB clusters showed a lower risk, while the HRHBP, HRBF, and HRIR clusters showed a higher risk of developing type 2 diabetes. The high-risk clusters, as a group, had a better predictive accuracy than prediabetes and adequate stability after 20 years.

Conclusions

Phenotypes derived using cluster analysis were useful in stratifying the risk of type 2 diabetes among diabetes-free adults in two independent cohorts. These results could be used to develop more precise public health interventions.
Mild pulmonary hemodynamic alterations in patients with systemic sclerosis: relevance of the new 2022 ESC/ERS definition of pulmonary hypertension and impact on mortality
Authors: Puigrenier Sébastien , Giovannelli Jonathan , Lamblin Nicolas , De Groote Pascal , Fertin Marie , Bervar Jean-François , Lamer Antoine , Edmé Jean-Louis , Balquet Marie-Hélène , Sobanski Vincent , Launay David , Hachulla Éric , Sanges Sébastien
Published: October 2022

Background and objective

The definition of pre-capillary pulmonary hypertension (PH) has been modified, with lowering of the mean pulmonary arterial pressure (mPAP) threshold from 25 to 20 mmHg and addition of a mandatory criterion of pulmonary vascular resistance (PVR) ≥ 2 Wood units (WU). Our objectives were: 1/ to estimate the proportion of patients reclassified as having pre-capillary PH when using the new 2022 ESC/ERS hemodynamic criteria (i.e. mPAP 21-24 mmHg and PVR ≥ 2 WU), and to describe their clinical characteristics and outcome; and 2/ to study the relationship between PVR and survival in patients with mPAP > 20 mmHg.

Methods

We retrospectively analyzed consecutive SSc patients included in our National Reference Center for a first right-heart catheterization between 2003 and 2018. The association between survival and PVR was studied using smoothing splines.

Results

We included 126 SSc patients with mPAP > 20 mmHg. Among them, 16 (13%) had a baseline mPAP value between 21 and 24 mmHg and PVR ≥ 2 mmHg and were reclassified as pre-capillary PH; 10 of which (62%) raised their mPAP ≥ 25 mmHg during follow-up. In patients with mPAP > 20 mmHg, we observed a linear relation between PVR and mortality for values < 6 WU.

Conclusion

A significant proportion of SSc patients is reclassified as having pre-capillary PH with the new 2022 ESC/ERS hemodynamic definition. Lowering the PVR threshold from 3 to 2 WU captures patients at risk of raising their mPAP > 25 mmHg, with a possibly less severe disease.
Microvascular complications identify a specific coronary atherosclerotic phenotype in patients with type 2 diabetes mellitus
Authors: Montone Rocco A. , Pitocco Dario , Gurgoglione Filippo Luca , Rinaldi Riccardo , Del Buono Marco Giuseppe , Camilli Massimiliano , Rizzi Alessandro , Tartaglione Linda , Rizzo Gaetano Emanuele , Di Leo Mauro , Flex Andrea , Russo Michele , Liuzzo Giovanna , Magnani Giulia , Bonadonna Riccardo C. , Ardissino Diego , Crea Filippo , Niccoli Giampaolo
Published: October 2022

Background

Patients with type 2 diabetes mellitus (T2DM) are considered as a homogeneous cohort of patients. However, the specific role of diabetic microvascular complications (DMC), in determining the features of coronary plaques is poorly known. We investigated whether the presence of DMC may identify a different phenotype of patients associated to specific clinical, angiographic, optical coherence tomography (OCT) features and different prognosis.

Methods

We prospectively enrolled consecutive T2DM patients with obstructive coronary artery disease (CAD) at their first coronary event. Patients were stratified according to the presence or absence of DMC, including diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. OCT assessment of the culprit vessel was performed in a subgroup of patients. The incidence of major adverse cardiac events (MACEs) was assessed at follow-up.

Results

We enrolled 320 T2DM patients (mean age 70.3 ± 8.8 years; 234 [73.1%] men, 40% acute coronary syndrome, 60% chronic coronary syndrome). Patients with DMC (172 [53.75%]) presented a different clinical and biochemical profile and, of importance, a higher prevalence of multivessel CAD (109 [63.4%] vs. 68 [45.9%], p = 0.002). At OCT analysis, DMC was associated to a higher prevalence of large calcifications and healed plaques and to a lower prevalence of lipid plaques. Finally, MACEs rate was significantly higher (25 [14.5%] vs. 12 [8.1%], p = 0.007) in DMC patients, mainly driven by a higher rate of planned revascularizations, and DMC predicted the occurrence of MACEs (mean follow-up 33.4 ± 15.6 months).

Conclusions

The presence of DMC identifies a distinct diabetic population with more severe CAD but with a more stable pattern of coronary atherosclerosis.
Response of circulating metabolites to an oral glucose challenge and risk of cardiovascular disease and mortality in the community
Authors: Gonzalez Izundegui Daniel , Miller Patricia E. , Shah Ravi V. , Clish Clary B. , Walker Maura E. , Mitchell Gary F. , Gerszten Robert E. , Larson Martin G. , Vasan Ramachandran S. , Nayor Matthew
Published: October 2022

Background

New biomarkers to identify cardiovascular disease (CVD) risk earlier in its course are needed to enable targeted approaches for primordial prevention. We evaluated whether intraindividual changes in blood metabolites in response to an oral glucose tolerance test (OGTT) may provide incremental information regarding the risk of future CVD and mortality in the community.

Methods

An OGTT (75 g glucose) was administered to a subsample of Framingham Heart Study participants free from diabetes (n = 361). Profiling of 211 plasma metabolites was performed from blood samples drawn before and 2 h after OGTT. The log2(post/pre) metabolite levels (Δmetabolites) were related to incident CVD and mortality in Cox regression models adjusted for age, sex, baseline metabolite level, systolic blood pressure, hypertension treatment, body mass index, smoking, and total/high-density lipoprotein cholesterol. Select metabolites were related to subclinical cardiometabolic phenotypes using Spearman correlations adjusted for age, sex, and fasting metabolite level.

Results

Our sample included 42% women, with a mean age of 56 ± 9 years and a body mass index of 30.2 ± 5.3 kg/m2. The pre- to post-OGTT changes (Δmetabolite) were non-zero for 168 metabolites (at FDR ≤ 5%). A total of 132 CVD events and 144 deaths occurred during median follow-up of 24.9 years. In Cox models adjusted for clinical risk factors, four Δmetabolites were associated with incident CVD (higher glutamate and deoxycholate, lower inosine and lysophosphatidylcholine 18:2) and six Δmetabolites (higher hydroxyphenylacetate, triacylglycerol 56:5, alpha-ketogluturate, and lower phosphatidylcholine 32:0, glucuronate, N-monomethyl-arginine) were associated with death (P < 0.05). Notably, baseline metabolite levels were not associated with either outcome in models excluding Δmetabolites. The Δmetabolites exhibited varying cross-sectional correlation with subclinical risk factors such as visceral adiposity, insulin resistance, and vascular stiffness, but overall relations were modest. Significant Δmetabolites included those with established roles in cardiometabolic disease (e.g., glutamate, alpha-ketoglutarate) and metabolites with less defined roles (e.g., glucuronate, lipid species).

Conclusions

Dynamic changes in metabolite levels with an OGTT are associated with incident CVD and mortality and have potential relevance for identifying CVD risk earlier in its development and for discovering new potential therapeutic targets.
Genome-wide identification of key enzyme-encoding genes and the catalytic roles of two 2-oxoglutarate-dependent dioxygenase involved in flavonoid biosynthesis in Cannabis sativa L.
Authors: Zhu Xuewen , Mi Yaolei , Meng Xiangxiao , Zhang Yiming , Chen Weiqiang , Cao Xue , Wan Huihua , Yang Wei , Li Jun , Wang Sifan , Xu Zhichao , Wahab Atia Tul , Chen Shilin , Sun Wei
Published: October 2022

Background

Flavonoids are necessary for plant growth and resistance to adversity and stress. They are also an essential nutrient for human diet and health. Among the metabolites produced in Cannabis sativa (C. sativa), phytocannabinoids have undergone extensive research on their structures, biosynthesis, and biological activities. Besides the phytocannabinoids, C. sativa is also rich in terpenes, alkaloids, and flavonoids, although little research has been conducted in this area.

Results

In this study, we identified 11 classes of key enzyme-encoding genes, including 56 members involved in the flavonoid biosynthesis in C. sativa, from their physical characteristics to their expression patterns. We screened the potentially step-by-step enzymes catalyzing the precursor phenylalanine to the end flavonoids using a conjoin analysis of gene expression with metabolomics from different tissues and chemovars. Flavonol synthase (FLS), belonging to the 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily, catalyzes the dihydroflavonols to flavonols. In vitro recombinant protein activity analysis revealed that CsFLS2 and CsFLS3 had a dual function in converting naringenin (Nar) to dihydrokaempferol (DHK), as well as dihydroflavonols to flavonols with different substrate preferences. Meanwhile, we found that CsFLS2 produced apigenin (Api) in addition to DHK and kaempferol when Nar was used as the substrate, indicating that CsFLS2 has an evolutionary relationship with Cannabis flavone synthase I.

Conclusions

Our study identified key enzyme-encoding genes involved in the biosynthesis of flavonoids in C. sativa and highlighted the key CsFLS genes that generate flavonols and their diversified functions in C. sativa flavonoid production. This study paves the way for reconstructing the entire pathway for C. sativa’s flavonols and cannflavins production in heterologous systems or plant culture, and provides a theoretical foundation for discovering new cannabis-specific flavonoids.
Enhancement of linalool production in Saccharomyces cerevisiae by utilizing isopentenol utilization pathway
Authors: Zhang Yaoyao , Cao Xianshuang , Wang Jin , Tang Feng
Published: October 2022

Background

Linalool is a monoterpenoid, also a vital silvichemical with commercial applications in cosmetics, flavoring ingredients, and medicines. Regulation of mevalonate (MVA) pathway metabolic flux is a common strategy to engineer Saccharomyces cerevisiae for efficient linalool production. However, metabolic regulation of the MVA pathway is complex and involves competition for central carbon metabolism, resulting in limited contents of target metabolites.

Results

In this study, first, a truncated linalool synthase (t26AaLS1) from Actinidia arguta was selected for the production of linalool in S. cerevisiae. To simplify the complexity of the metabolic regulation of the MVA pathway and increase the flux of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), we introduced the two-step isopentenyl utilization pathway (IUP) into S. cerevisiae, which could produce large amounts of IPP/DMAPP. Further, the S. cerevisiae IDI1 (ecoding isopentenyl diphosphate delta-isomerase) and ERG20F96W−N127W (encoding farnesyl diphosphate synthase) genes were integrated into the yeast genome, combined with the strategies of copy number variation of the t26AaLS1 and ERG20F96W−N127W genes to increase the metabolic flux of the downstream IPP, as well as optimization of isoprenol and prenol concentrations, resulting in a 4.8-fold increase in the linalool titer. Eventually, under the optimization of carbon sources and Mg2+ addition, a maximum linalool titer of 142.88 mg/L was obtained in the two-phase extractive shake flask fermentation.

Conclusions

The results show that the efficient synthesis of linalool in S. cerevisiae could be achieved through a two-step pathway, gene expression adjustment, and optimization of culture conditions. The study may provide a valuable reference for the other monoterpenoid production in S. cerevisiae.