Optimal decision-making in relieving global high temperature-related disease burden by data-driven simulation.

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010-2019. The burdens of five categories of disease causes - cardiovascular diseases, infectious respiratory diseases, injuries, metabolic diseases, and non-infectious respiratory diseases - were designated as intermediate outcome variables. The cumulative burden of these five categories, referred to as the total HTD burden, was the final outcome variable. We evaluated the predictive performance of eight models and subsequently introduced twelve intervention measures, allowing us to explore optimal decision-making strategies and assess their corresponding contributions. Our model selection results demonstrated the superior performance of the Graph Neural Network (GNN) model across various metrics. Utilizing simulations driven by the GNN model, we identified a set of optimal intervention strategies for reducing disease burden, specifically tailored to the seven major regions: East Asia and Pacific, Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. Sectoral mitigation and adaptation measures, acting upon our categories of Infrastructure & Community, Ecosystem Resilience, and Health System Capacity, exhibited particularly strong performance for various regions and diseases. Seven out of twelve interventions were included in the optimal intervention package for each region, including raising low-carbon energy use, increasing energy intensity, improving livestock feed, expanding basic health care delivery coverage, enhancing health financing, addressing air pollution, and improving road infrastructure. The outcome of this study is a global decision-making tool, offering a systematic methodology for policymakers to develop targeted intervention strategies to address the increasingly severe challenge of HTDs in the context of global warming.

Advancements in fertility preservation strategies for pediatric male cancer patients: a review of cryopreservation and transplantation of immature testicular tissue.

Recently, there has been increasing emphasis on the gonadotoxic effects of cancer therapy in prepubertal boys. As advances in oncology treatments continue to enhance survival rates for prepubertal boys, the need for preserving their functional testicular tissue for future reproduction becomes increasingly vital. Therefore, we explore cutting-edge strategies in fertility preservation, focusing on the cryopreservation and transplantation of immature testicular tissue as a promising avenue. The evolution of cryopreservation techniques, from controlled slow freezing to more recent advancements in vitrification, with an assessment of their strengths and limitations was exhibited. Detailed analysis of cryoprotectants, exposure times, and protocols underscores their impact on immature testicular tissue viability. In transplantation strategy, studies have revealed that the scrotal site may be the preferred location for immature testicular tissue grafting in both autotransplantation and xenotransplantation scenarios. Moreover, the use of biomaterial scaffolds during graft transplantation has shown promise in enhancing graft survival and stimulating spermatogenesis in immature testicular tissue over time. This comprehensive review provides a holistic approach to optimize the preservation strategy of human immature testicular tissue in the future.

The impact of COVID-19 and other factors on the usage status of the biologic drug therapies for rheumatoid arthritis: A study from Vietnam / El impacto de COVID-19 y otros factores en el estado de uso de las terapias farmacológicas biológicas para la artritis reumatoide: un estudio de Vietnam

Objectives: To describe the status of using biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) to treat rheumatoid arthritis (RA) and related factors. In addition, the study determined the impact of COVID-19 on the usage of bDMARDs. Methods: This is a cross-sectional study and included 219 RA patients over 18 years old. The Kaplan–Meier method and the log-rank test (p<0.05) were used to estimate the retention time and compare between different times. Cox regression analysis was used to determine the factors affecting the retention time of biological drugs (p<0.05). Results: Out of 1967 courses of treatment, there were 149 (7.6%) drug discontinuations, 760 (38.6%) doses extensions and 64 (3.3%) drug switch. Moderate disease level and choosing tumor necrosis factor (TNF) inhibitors initially were associated with retention time of COVID-19. Drug discontinuations and dose extensions increased after COVID-19 emergence. The retention time during COVID-19 was significantly different from that of pre-COVID-19. Gender, type of first-used bDMARD, conventional synthetic DMARDs (csDMARDs) and corticoid usage status, disease activity levels were associated with retention time. Conclusion: The presence of COVID-19 has a significant effect on usage status of the biologic drug. Further longitudinal studies are needed to clarify the relationship between COVID-19 and drug usage as well as related factors.(AU)

Objetivos: Describir el estado del uso de fármacos antirreumáticos modificadores de la enfermedad biológica (bDMARD) para tratar la artritis reumatoide (AR) y los factores relacionados. Además, el estudio determinó el impacto de COVID-19 en el uso de bDMARD. Métodos: Este es un estudio transversal que incluyó a 219 pacientes con AR mayores de 18 años. El método Kaplan-Meier y la prueba Log-rank (p<0,05) se usaron para estimar el tiempo de retención y compararlo entre diferentes tiempos. El análisis de regresión de Cox se utilizó para determinar los factores que afectan el tiempo de retención de los medicamentos biológicos (p<0,05). Resultados: De 1.967 cursos de tratamiento, hubo 149 (7,6%) interrupciones del fármaco, 760 (38,6%) extensiones de dosis y 64 (3,3%) cambios de fármaco. Nivel de enfermedad moderado y elección del factor de necrosis tumoral (TNF) inhibidores inicialmente se asociaron con el tiempo de retención de COVID-19. Las discontinuaciones de los medicamentos y las extensiones de las dosis aumentaron después de la aparición de COVID-19. El tiempo de retención durante COVID-19 fue significativamente diferente del pre-COVID-19. Género, tipo de bDMARD de primer uso, convencional DMARD sintéticos (csDMARDs) y el estado de uso de corticoides, los niveles de actividad de la enfermedad se asociaron con el tiempo de retención. Conclusión: La presencia de COVID-19 tiene un efecto significativo en el estado de uso del medicamento biológico. Se necesitan más estudios longitudinales para aclarar la relación entre COVID-19 y el uso de fármacos, así como los factores relacionados.(AU)

Risk Factors for Postoperative Cognitive Decline After Orthopedic Surgery in Elderly Chinese Patients: A Retrospective Cohort Study.

Purpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions. Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation-Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥1 point between the preoperative and postoperative scale was defined as POCD. Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028-5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057-0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively. Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.

Homocysteine modifies the association of coronary stenosis and HIV infection in an inner city African American population.

BACKGROUND AND AIMS: People with HIV (PWH) whose disease is controlled on anti-retroviral regimens remain at an increased risk for coronary artery disease (CAD). Traditional cardiovascular risk factors do not fully explain the residual risk in PWH suggesting contributions from nontraditional factors. Homocysteine (Hcy) may be one of these as prior work in adults without HIV demonstrate that Hcy may impair endothelial function by decreasing the availability of nitric oxide, promoting the development of atherosclerosis. In addition, plasma Hcy levels are higher in PWH than in individuals living without HIV. The aim of this study was to investigate whether Hcy levels influence the association between HIV and coronary stenosis in an inner city African American population. METHODS: African Americans from the Heart Study in Baltimore, with and without HIV, recruited from inner-city Baltimore between June 2004 and February 2015, were included in this analysis. Participants underwent coronary CT angiography to evaluate the presence of coronary stenosis, defined as luminal stenosis >10%. Hcy was measured from stored serum samples. RESULTS: In this analysis, the median [IQR] age of the 664 participants was 56 [50-66] years; 68.1% were living with HIV and 43.1% were women. Elevated Hcy (>15 µmol/L) was more prevalent in those with coronary stenosis (23.3%, 95% CI: 18.4%-28.2%) than in those without coronary stenosis (13.1%, 95% CI: 9.7%-16.5%) (p = 0.0007), and HIV was associated with coronary stenosis in those participants with an elevated Hcy (Prevalence Ratio: 1.94, 95% CI: 1.04-3.64, p = 0.0038) and not in those with a Hcy ≤15 µmol/L (Prevalence Ratio: 1.02, 95% CI: 0.83-1.25, p = 0.87). CONCLUSIONS: Our data suggest an association between elevated Hcy levels (>15 µmol/L) and the prevalence of coronary stenosis in PWH from this inner city African American population.

Accuracy of robotic surgery for dental implant placement: A systematic review and meta-analysis.

OBJECTIVES: To systematically analyze the accuracy of robotic surgery for dental implant placement. MATERIALS AND METHODS: PubMed, Embase, and Cochrane CENTRAL were searched on October 25, 2023. Model studies or clinical studies reporting the accuracy of robotic surgery for dental implant placement among patients with missing or hopeless teeth were included. Risks of bias in clinical studies were assessed. Meta-analyses were undertaken. RESULTS: Data from 8 clinical studies reporting on 109 patients and 242 implants and 13 preclinical studies were included. Positional accuracy was measured by comparing the implant plan in presurgery CBCT and the actual implant position in postsurgery CBCT. For clinical studies, the pooled (95% confidence interval) platform deviation, apex deviation, and angular deviation were 0.68 (0.57, 0.79) mm, 0.67 (0.58, 0.75) mm, and 1.69 (1.25, 2.12)°, respectively. There was no statistically significant difference between the accuracy of implants placed in partially or fully edentulous patients. For model studies, the pooled platform deviation, apex deviation, and angular deviation were 0.72 (0.58, 0.86) mm, 0.90 (0.74, 1.06) mm, and 1.46 (1.22, 1.70)°, respectively. No adverse event was reported. CONCLUSION: Within the limitation of the present systematic review, robotic surgery for dental implant placement showed suitable implant positional accuracy and had no reported obvious harm. Both robotic systems and clinical studies on robotic surgery for dental implant placement should be further developed.

Does intra-oral scan improve the impression accuracy of full-arch implant-supported prostheses: A systematic review and meta-analysis.

OBJECTIVES: The present study aimed to systematically review the studies comparing the accuracy of intraoral scan (IOS) and conventional implant impressions (CI) in completely edentulous patients. MATERIALS AND METHODS: Electronic searches were performed in PubMed, Embase and Cochrane CENTRAL up to December 1, 2023. Clinical studies and in vitro studies reporting the accuracy of digital full arch impressions were included. The primary outcome is the 3-dimensional deviations between the study reference models. A risk of bias assessment was performed for clinical studies. A stratified meta-analysis and a single-armed meta-analysis were conducted. RESULTS: A total of 49 studies were included, with 8 clinical studies and 41 in vitro studies. For comparison between IOS and conventional impressions, studies were categorized into two groups based on the different measurement methods employed: RMS and CMM. In studies using RMS, the result favored the IOS in the unparalleled situation with the mean difference of -99.29 µm (95% CI: [-141.38, -57.19], I2 = 81%), while the result was opposite with the mean difference of 13.62 µm (95% CI: [10.97, 16.28], I2 = 26%) when implants were paralleled. For different brands of IOS, the accuracy ranged from 76.11 µm (95% CI: [42.36, 109.86]) to 158.63 µm (95% CI: [-14.68, 331.93]). CONCLUSIONS: Accuracy of intraoral scan is clinically acceptable in edentulous arches, especially for unparalleled implants. More clinical studies are needed to verify the present finding.

Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice.

BACKGROUND: Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function. RESULTS: We demonstrated that QSOX2 was detected in the follicle-supporting cells (granulosa and cumulus cells) of ovarian follicles of all stages but was absent in the corpus luteum, suggesting its supportive role in folliculogenesis. In comparison with reproductive organogenesis in wild-type mice, there was no difference in testicular and epididymal structure in male Qsox2 knockout; however, Qsox2 knockout disrupted the regular ovulation process in female mice as a drastic decrease in the formation of the corpus luteum was detected, and no pregnancy was achieved when mating males with homozygous Qsox2 knockout females. RNAseq analyses further revealed that Qsox2 knockout altered critical signaling pathways and genes that are responsible for maintaining ovarian functions. CONCLUSION: Our data demonstrated for the first time that Qsox2 is critical for ovarian function in mice.

Pyruvate is modified by tea/coffee metabolites and reversely correlated with multiple system atrophy and Parkinson's disease.

Introduction: Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder. Although diverse biomarkers have been established for Parkinson's disease (PD), no widely accepted markers have been identified in MSA. Pyruvate and lactate are the end-product of glycolysis and crucial for brain metabolism. However, their correlation with MSA remains unclear. Moreover, it is elusive how lifestyles modify these metabolites. Methods: To investigate the correlation and diagnostic value of plasma pyruvate and lactate levels in MSA and PD. Moreover, we explored how lifestyle-related metabolites interact with these metabolites in determining the disease risk. We assayed the 3 metabolites in pyruvate/lactate and 6 in the tea/coffee metabolic pathways by targeted mass spectrometry and evaluate their interactions and performance in diagnosis and differentiation between MSA and PD. Results: We found that 7 metabolites were significantly different between MSA, PD and healthy controls (HCs). Particularly, pyruvate was increased in PD while significantly decreased in MSA patients. Moreover, the tea/coffee metabolites were negatively associated with the pyruvate level in HCs, but not in MSA and PD patients. Using machine-learning models, we showed that the combination of pyruvate and tea/coffee metabolites diagnosed MSA (AUC = 0.878) and PD (AUC = 0.833) with good performance. Additionally, pyruvate had good performance in distinguishing MSA from PD (AUC = 0.860), and the differentiation increased (AUC = 0.922) when combined with theanine and 1,3-dimethyluric acid. Conclusions: This study demonstrates that pyruvate correlates reversely with MSA and PD, and may play distinct roles in their pathogenesis, which can be modified by lifestyle-related tea/coffee metabolites.

The impact of COVID-19 and other factors on the usage status of the biologic drug therapies for rheumatoid arthritis: A study from Vietnam.

OBJECTIVES: To describe the status of using biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) to treat rheumatoid arthritis (RA) and related factors. In addition, the study determined the impact of COVID-19 on the usage of bDMARDs. METHODS: This is a cross-sectional study and included 219 RA patients over 18 years old. The Kaplan-Meier method and the log-rank test (p<0.05) were used to estimate the retention time and compare between different times. Cox regression analysis was used to determine the factors affecting the retention time of biological drugs (p<0.05). RESULTS: Out of 1967 courses of treatment, there were 149 (7.6%) drug discontinuations, 760 (38.6%) doses extensions and 64 (3.3%) drug switch. Moderate disease level and choosing tumor necrosis factor (TNF) inhibitors initially were associated with retention time of COVID-19. Drug discontinuations and dose extensions increased after COVID-19 emergence. The retention time during COVID-19 was significantly different from that of pre-COVID-19. Gender, type of first-used bDMARD, conventional synthetic DMARDs (csDMARDs) and corticoid usage status, disease activity levels were associated with retention time. CONCLUSION: The presence of COVID-19 has a significant effect on usage status of the biologic drug. Further longitudinal studies are needed to clarify the relationship between COVID-19 and drug usage as well as related factors.

Impact of preoperative factors and waiting time on post-appendectomy complications: a retrospective study.

BACKGROUND: Several factors are associated with increased postoperative complications after appendectomies. However, few studies combined these potential factors for comprehensive prediction of surgical outcomes. Whether high-risk patients benefit from a shorter waiting time for surgery remains unclear. This study aimed to explore the impact of surgical waiting time and potential risk factors on postoperative complications. METHODS: A total of 1343 patients diagnosed with acute appendicitis requiring an emergent appendectomy were included from 2013 to 2018. The preoperative risk factors associated with postoperative complications were selected and the probability of postoperative complications was calculated by multivariate logistic regression model. Patients were divided into four groups based on the risk (high & low) and time to surgery (> 12 & ≤12 hours). The odds ratios for complications were evaluated between groups. RESULTS: The selected risk factors included age, neutrophil-lymphocyte ratio, systemic inflammatory response syndrome and abdominal pain duration. Compared with low-risk patients with time to surgery ≤12 hours, high-risk patients with time to surgery > 12 hours had significant increased overall postoperative complication rate (16.85% vs. 8.16%, p = 0.002) and a trend toward increased surgical site infection rate (10.99% vs. 6.46%, p = 0.058). When operated within 12 hours, there was no difference in outcomes between high- and low-risk patients. On the other hand, time to surgery > 12 hours did not increase complication rate in low-risk patients. CONCLUSIONS: The surgical outcome may be affected by preoperative factors and time to surgery. It is suggested that high-risk patients receive appendectomy within 12 hours to avoid increased postoperative complications.

REG3A overexpression functions as a negative predictive and prognostic biomarker in rectal cancer patients receiving CCRT.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patient-specific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis. METHODS: A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups. RESULTS: Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis. CONCLUSION: In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decision-making more accurately for those patients.

Elevated homocysteine levels may moderate and mediate the association between HIV and cognitive impairment among middle-aged and older adults in an underserved population in Baltimore, Maryland.

Background: In the antiretroviral therapy (ART) era, HIV-associated neurocognitive disorders (HAND) remain a considerable challenge for people with HIV, yet not all such disorders can be attributed to HIV alone. This study aimed to: (1) identify factors influencing neurocognitive impairment (NCI) utilizing the NIH Toolbox Cognition Battery (NIHTB-CB) as per the revised research criteria for HAND; (2) ascertain the moderating role of high homocysteine levels in the association between NCI and HIV; and (3) assess the mediating effect of elevated homocysteine levels on this association.Methods: We analyzed data from 788 adults (≥45 years) participating in a study on HIV-related comorbidities in underserved Baltimore communities, using NIHTB-CB to gauge neurocognitive performance. Special attention was given to results from the Dimensional Change Card Sort (DCCS) test within the executive function domain during causal mediation analysis.Results: Overall, HIV was not associated with NCI presence. However, HIV was associated with NCI among individuals with homocysteine >14 µmol/L. Furthermore, HIV was both directly and indirectly associated with NCI in DCCS test scores. Notably, the mediating role of elevated homocysteine in DCCS scores was only observable among individuals who had never used cocaine or had used it for ≤ 10 years, suggesting that extended cocaine use may have a substantial influence on cognitive performance.Conclusions: The findings from this study suggest elevated homocysteine levels may moderate and mediate the association between HIV and neurocognitive impairment.

Combining multimodal magnetic resonance brain imaging and machine learning to unravel neurocognitive function in non-neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To study whether multimodal brain MRI comprising permeability and perfusion measures coupled with machine learning can predict neurocognitive function in young patients with SLE without neuropsychiatric manifestations. METHODS: SLE patients and healthy controls (HCs) (≤40 years of age) underwent multimodal structural brain MRI that comprised voxel-based morphometry (VBM), magnetization transfer ratio (MTR) and dynamic contrast-enhanced (DCE) MRI in this cross-sectional study. Neurocognitive function assessed by Automated Neuropsychological Assessment Metrics was reported as the total throughput score (TTS). Olfactory function was assessed. A machine learning-based model (i.e. glmnet) was constructed to predict TTS. RESULTS: Thirty SLE patients and 10 HCs were studied. Both groups had comparable VBM, MTR, olfactory bulb volume (OBV), olfactory function and TTS. While after correction for multiple comparisons the uncorrected increase in the blood-brain barrier (BBB) permeability parameters compared with HCs did not remain evident in SLE patients, DCE-MRI perfusion parameters, notably an increase in right amygdala perfusion, was positively correlated with TTS in SLE patients (r = 0.636, false discovery rate P < 0.05). A machine learning-trained multimodal MRI model comprising alterations of VBM, MTR, OBV and DCE-MRI parameters mainly in the limbic system regions predicted TTS in SLE patients (r = 0.644, P < 0.0005). CONCLUSION: Multimodal brain MRI demonstrated increased right amygdala perfusion that was associated with better neurocognitive performance in young SLE patients without statistically significant BBB leakage and microstructural abnormalities. A machine learning-constructed multimodal model comprising microstructural, perfusion and permeability parameters accurately predicted neurocognitive performance in SLE patients.

Improved positional accuracy of dental implant placement using a haptic and machine-vision-controlled collaborative surgery robot: A pilot randomized controlled trial.

AIM: To compare the implant accuracy, safety and morbidity between robot-assisted and freehand dental implant placement. MATERIALS AND METHODS: Subjects requiring single-site dental implant placement were recruited. Patients were randomly allocated to freehand implant placement and robot-assisted implant placement. Differences in positional accuracy of the implant, surgical morbidity and complications were assessed. The significance of intergroup differences was tested with an intention-to-treat analysis and a per-protocol (PP) analysis (excluding one patient due to calibration error). RESULTS: Twenty patients (with a median age of 37, 13 female) were included. One subject assigned to the robotic arm was excluded from the PP analysis because of a large calibration error due to the dislodgement of the index. For robot-assisted and freehand implant placement, with the PP analysis, the median (25th-75th percentile) platform global deviation, apex global deviation and angular deviation were 1.23 (0.9-1.4) mm/1.9 (1.2-2.3) mm (p = .03, the Mann-Whitney U-test), 1.40 (1.1-1.6) mm/2.1 (1.7-3.9) mm (p < .01) and 3.0 (0.9-6.0)°/6.7 (2.2-13.9)° (p = .08), respectively. Both methods showed limited damage to the alveolar ridge and had similar peri- and post-operative morbidity and safety. CONCLUSIONS: Robot-assisted implant placement enabled greater positional accuracy of the implant compared to freehand placement in this pilot trial. The robotic system should be further developed to simplify surgical procedures and improve accuracy and be validated in properly sized trials assessing the full spectrum of relevant outcomes.

Association of serum 25-hydroxyvitamin D levels with aggressiveness of papillary thyroid cancer.

Objective: Serum 25-hydroxyvitamin D (25(OH)D) deficiency has been known to be associated with the risk and mortality of several cancers. However, the role of 25(OH)D in papillary thyroid cancer (PTC) remains controversial. This study aimed to investigate the association between 25(OH)D and clinicopathologic features of PTC. Methods: Patients who underwent thyroidectomy were retrospectively reviewed. Serum 25(OH)D levels were measured within a week prior to surgery. The patients were categorized into four quartiles according to season-specific 25(OH)D levels. The association between 25(OH)D levels and clinicopathologic features of PTC was analyzed. Results: A total of 2932 patients were enrolled in the study. The 25(OH)D levels were significantly higher in patients with lymph node metastasis (LNM; P < 0.001), lateral LNM (P < 0.001), and multifocal tumors (P < 0.001). Compared to the first quartile (Q1) of 25(OH)D level, the third quartile (Q3) and the fourth quartile (Q4) showed an unadjusted OR of 1.36 (95% CI: 1.09-1.69; P = 0.006) and 1.76 (95% CI: 1.42-2.19; P < 0.001) for LNM (P for trend < 0.001), respectively. An increased risk of multifocal tumors was strongly associated with high 25(OH)D concentration (P for trend <0.001). Similar results were obtained after adjusting for confounding factors. Conclusion: High 25(OH)D levels are associated with aggressive features of PTC, such as lymph node metastasis and multifocality.

Ubiquitin-conjugating enzyme E2C (UBE2C) is a prognostic indicator for cholangiocarcinoma.

Cholangiocarcinoma is the most common malignant bile duct tumor in Southeast Asia. The special location of cholangiocarcinoma leads to it being difficult to diagnose. Currently, the progress in clinical prognosis outcomes remains abysmal owing to the lack of definitive diagnostic criteria. Therefore, uncovering the potential markers for cholangiocarcinoma is a pressing issue. Ubiquitin-conjugating enzyme E2 C (UBE2C) is a critical ubiquitination enzyme; it is involved in the tumorigenesis of various malignancies and affects the patient's prognosis. However, there is currently no relevant literature to indicate whether UBE2C is related to the clinical survival outcome of cholangiocarcinoma patients. In this report, we mined the published cholangiocarcinoma transcriptome data set (GSE26566), compared it with the ubiquitination-associated gene (GO:0016567), and identified that UBE2C was highly expressed in cholangiocarcinoma tumor tissue. Moreover, high expression of UBE2C was markedly correlated with surgical margin, primary tumor, histological variants, and histological grade. More specifically, high expression of UBE2C was negatively associated with overall survival, disease-specific survival, local recurrence-free survival, and metastasis-free survival in patients with cholangiocarcinoma. Our findings demonstrate that UBE2C may provide a potential therapeutic marker and prognostic factor for cholangiocarcinoma patients.

ACO2 deficiency increases vulnerability to Parkinson's disease via dysregulating mitochondrial function and histone acetylation-mediated transcription of autophagy genes.

Parkinson's disease (PD) is characterized by α-synuclein aggregation in dopaminergic (DA) neurons, which are sensitive to oxidative stress. Mitochondria aconitase 2 (ACO2) is an essential enzyme in the tricarboxylic acid cycle that orchestrates mitochondrial and autophagic functions to energy metabolism. Though widely linked to diseases, its relation to PD has not been fully clarified. Here we revealed that the peripheral ACO2 activity was significantly decreased in PD patients and associated with their onset age and disease durations. The knock-in mouse and Drosophila models with the A252T variant displayed aggravated motor deficits and DA neuron degeneration after 6-OHDA and rotenone-induction, and the ACO2 knockdown or blockade cells showed features of mitochondrial and autophagic dysfunction. Moreover, the transcription of autophagy-related genes LC3 and Atg5 was significantly downregulated via inhibited histone acetylation at the H3K9 and H4K5 sites. These data provided multi-dimensional evidences supporting the essential roles of ACO2, and as a potential early biomarker to be used in clinical trials for assessing the effects of antioxidants in PD. Moreover, ameliorating energy metabolism by targeting ACO2 could be considered as a potential therapeutic strategy for PD and other neurodegenerative disorders.

Delayed Collagen Production without Myofibroblast Formation Contributes to Reduced Scarring in Adult Skin Microwounds.

In adult mammals, wound healing predominantly follows a fibrotic pathway, culminating in scar formation. However, cutaneous microwounds generated through fractional photothermolysis, a modality that produces a constellation of microthermal zones, exhibit a markedly different healing trajectory. Our study delineates the cellular attributes of these microthermal zones, underscoring a temporally limited, subclinical inflammatory milieu concomitant with rapid re-epithelialization within 24 hours. This wound closure is facilitated by the activation of genes associated with keratinocyte migration and differentiation. In contrast to macrothermal wounds, which predominantly heal through a robust myofibroblast-mediated collagen deposition, microthermal zones are characterized by absence of wound contraction and feature delayed collagen remodeling, initiating 5-6 weeks after injury. This distinct wound healing is characterized by a rapid re-epithelialization process and a muted inflammatory response, which collectively serve to mitigate excessive myofibroblast activation. Furthermore, we identify an initial reparative phase characterized by a heterogeneous extracellular matrix protein composition, which precedes the delayed collagen remodeling. These findings extend our understanding of cutaneous wound healing and may have significant implications for the optimization of therapeutic strategies aimed at mitigating scar formation.

LAMC2 is a potential prognostic biomarker for cholangiocarcinoma.

Cholangiocarcinoma is a common malignancy with increasing incidence worldwide. Most patients are diagnosed at the advanced stage with poor survival rate. Laminin subunit γ2 (LAMC2) is a heparin binding-associated gene involved in tumorigenesis and has been implicated in the prognosis of various types of cancers. However, it is unclear whether expression of LAMC2 is associated with the clinical outcome of patients with cholangiocarcinoma. In the present study, the role and prognostic value of LAMC2 expression in patients with cholangiocarcinoma was investigated. Clinical information and pathological characteristics were analyzed and the association between LAMC2 expression and clinical characteristics, pathological findings and patient outcomes, including metastasis-free and disease-specific survival, were investigated. Data from 182 patients with cholangiocarcinoma were evaluated. High LAMC2 expression was associated with higher tumor stage (P<0.001), large duct type (P=0.024) and poor histological grade (P=0.002). Kaplan-Meier analysis showed high LAMC2 expression was associated with lower overall (P=0.003), disease-specific (P=0.0025), local recurrence-free (P<0.0001) and metastasis-free survival (P<0.0001). Moreover, multivariate analysis demonstrated that increased LAMC2 expression was a significant predictive risk factor for overall [hazard ratio (HR) 1.713; P=0.034], disease-specific (HR 2.011; P=0.039), local recurrence-free (HR 2.721; P<0.001) and metastasis-free survival (HR 3.117; P<0.001). Gene enrichment analysis using Gene Ontology showed that terms associated with LAMC2 upregulation were 'regulation of platelet-derived growth factor receptor-ßsignaling pathway' and 'platelet-derived growth factor receptor-ß signaling pathway'. The present study indicated that LAMC2 was upregulated in cholangiocarcinoma tumor tissue and had an inverse association with overall, disease-specific, local recurrence-free and metastasis-free survival in patients with cholangiocarcinoma. These results suggested that LAMC2 may serve as a potential biomarker for cholangiocarcinoma.