Machine learning applications in breast cancer survival and therapeutic outcome prediction based on multi-omic analysis.

The high heterogeneity within and between breast cancer patients complicates treatment determination and prognosis assessment. Treatment decision-making is influenced by various factors, such as tumor subtype, histological grade, and genotype, necessitating personalized treatment strategies. Prognostic outcomes vary significantly depending on patient-specific conditions. As a critical branch of artificial intelligence, machine learning efficiently handles large datasets and automates decision-making processes. The introduction of machine learning offers new solutions for breast cancer treatment selection and prognosis assessment. In the field of cancer therapy, traditional methods for predicting treatment and survival outcomes often rely on single or few biomarkers, limiting their ability to capture the complexity of biological processes comprehensively. Machine learning analyzes patients' multi-omic data and the intricate patterns of variations during cancer initiation and progression to predict patients' survival and treatment outcomes. Consequently, it facilitates the selection of appropriate therapeutic interventions to implement early intervention and improve treatment efficacy for patients. Here, we first introduce common machine learning methods, and then elaborate on the application of machine learning in the field of survival prediction and prognosis from two aspects: evaluating survival and predicting treatment outcomes for breast cancer patients. The aim is to provide breast cancer patients with precise treatment strategies to improve therapeutic outcomes and quality of life.

Associations between peripheral whole blood cell counts derived indexes and cancer prognosis: An umbrella review of meta-analyses of cohort studies.

Meta-analyses have reported conflicting data on the whole blood cell count (WBCC) derived indexes (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and lymphocyte-to-monocyte ratio [LMR]) and cancer prognosis. However, the strength and quality of this evidence has not been quantified in aggregate. To grade the evidence from published meta-analyses of cohort studies that investigated the associations between NLR, PLR, and LMR and cancer prognosis. A total of 694 associations from 224 articles were included. And 219 (97.8%) articles rated as moderate-to-high quality according to AMSTAR. There were four associations supported by convincing evidence. Meanwhile, 165 and 164 associations were supported by highly suggestive and suggestive evidence, respectively. In this umbrella review, we summarized the existing evidence on the WBCC-derived indexes and cancer prognosis. Due to the direction of effect sizes is not completely consistent between studies, further research is needed to assess causality and provide firm evidence.

Retrograde transurethral injection of indocyanine green better assists complete transperitoneal nephroureterectomy in a single-position.

Background: Complete transperitoneal nephroureterectomy (CTNU) in a single-position is an advanced surgical technique for the treatment of upper urinary tract urothelial carcinoma (UTUC), performed entirely through a transperitoneal approach without the need for patient repositioning. Indocyanine green (ICG) has been extensively studied in urologic surgery, with applications ranging from sentinel lymph node mapping to tumor localization. This study aimed to evaluate the performance of retrograde ureteral fluorescence imaging in CTNU. Methods: This retrospective cohort enrolled 81 patients diagnosed with UTUC and underwent single-position CTNU. Cohorts were divided into two groups according to whether the ICG was applied. Perioperative data and oncology outcomes were recorded and analyzed. Results: In total, 81 eligible participants were finally included, with 40 in the ICG group and 41 in the non-ICG group. The ICG group presented significantly shorter ureter identification time (8.5±3.3 vs. 17.3±4.2 min, P<0.001) and duration of surgery (132±40 vs. 162±49 min, P=0.003), as well as lower estimated blood loss (EBL) (108±94 vs. 183±126 mL, P=0.003) compared to the non-ICG group. The rates of intravesical and extravesical carcinoma recurrence were comparable between the two groups. At a median follow-up of 16.7 months, there were no significant differences in terms of the recurrence-free survival (RFS) and overall survival (OS) between groups. Conclusions: ICG guided ureteral fluorescence imaging in single-position CTNU showed significant advantages in precisely and effectively locating the ureter, with improved surgical outcomes. Meanwhile, the enhanced visualization of the ureteral intramural segment and bladder cuff facilitated the complete removal of the specimen en bloc and the watertight closure of the bladder.

Urinary heavy metals and overall survival of advanced high-grade serous ovarian cancer: A nested case-control study in China.

BACKGROUND: Environmental pollution has emerged as a significant determinant in ovarian cancer prognosis. However, limited evidence exists regarding the correlations between heavy metals and ovarian cancer prognosis. OBJECTIVE: To elucidate the relationship between urinary heavy metals and their mixtures with overall survival (OS) of advanced high-grade serous ovarian cancer (HGSOC). METHODS: Within the Ovarian Cancer Follow-Up Study, we conducted a nested case-control study. A sum of 159 deceased patients and an equal number of alive patients were included, matched by sample date, body mass index, and age at diagnosis. Urinary concentrations of five heavy metals were quantified: arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). Conditional logistic regression models were employed to calculate odds ratios (ORs) and their 95 % confidence intervals (CIs). To elucidate joint effects, we utilized quantile g-computation and Bayesian kernel machine regression models. RESULTS: For the multivariable adjusted conditional logistic regression model, significant associations were found between high urinary levels of As (OR=1.99, 95 %CI: 1.05-3.79), Cd (OR=2.56, 95 %CI: 1.29-5.05), Hg (OR=2.24, 95 %CI: 1.09-4.62), and Pb (OR=3.80, 95 %CI: 1.75-8.27) and worse OS of HGSOC, comparing the highest tertile to the lowest. Analysis of joint effects showed that elevated concentrations of heavy metal mixtures were related to poor OS of HGSOC. Pb exhibited the highest contribution to the overall association within the metal mixtures. CONCLUSIONS: High urinary heavy metal concentrations were linked to worse OS of HGSOC. Future research is necessary to validate our findings.

Association between pre-diagnosis and post-diagnosis Alternate Mediterranean Diet and ovarian cancer survival: evidence from a prospective cohort study.

BACKGROUND: There is currently a lack of comprehensive evidence regarding the correlation between Alternate Mediterranean Diet (AMED) and the survival of patients with ovarian cancer (OC). This prospective cohort study first assessed the association of AMED, not only pre-diagnosis and post-diagnosis but also the change from pre-diagnosis to post-diagnosis with OC survival. METHODS: A total of 560 OC patients were included in the study, and their dietary intake was assessed using a reliable 111-item food frequency questionnaire. The overall survival (OS) of the patients was monitored through active follow-up and review of medical records until February 16th, 2023. Cox proportional hazard regression models were utilized to compute the hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). RESULTS: Out of the total 560 patients with OC, 211 (37.68%) succumbed during a median follow-up period of 44.40 months (interquartile range: 26.97-61.37). Comparative analysis indicated a significant association between the highest tertiles of pre-diagnosis (HR = 0.59; 95% CI 0.38-0.90; Ptrend < 0.05) and post-diagnosis (HR = 0.61; 95% CI 0.41-0.91; Ptrend < 0.05) AMED intake and improved OS as opposed to the lowest tertile. Additionally, a significant linear trend was observed for AMED and OC survival. Notably, decreased intake (more than 5% change) and significantly increased intake (more than 15% change) of AMED from pre-diagnosis to post-diagnosis were linked to worse and better OS, respectively, when compared to the stable intake group (change within 5%). Furthermore, patients displaying consistently higher AMED intake both before and after diagnosis experienced enhanced OS in comparison to those with consistently low AMED intake (HRHigh-High vs. Low-Low = 0.47; 95% CI 0.31-0.70). CONCLUSION: High pre-diagnosis and post-diagnosis AMED was associated with an improved OS in patients with OC, suggesting that maintaining a consistently high intake of AMED could potentially benefit the prognosis of OC.

Dynamic memristor for physical reservoir computing.

Reservoir computing (RC) has attracted considerable attention for its efficient handling of temporal signals and lower training costs. As a nonlinear dynamic system, RC can map low-dimensional inputs into high-dimensional spaces and implement classification using a simple linear readout layer. The memristor exhibits complex dynamic characteristics due to its internal physical processes, which renders them an ideal choice for the implementation of physical reservoir computing (PRC) systems. This review focuses on PRC systems based on memristors, explaining the resistive switching mechanism at the device level and emphasizing the tunability of their dynamic behavior. The development of memristor-based reservoir computing systems is highlighted, along with discussions on the challenges faced by this field and potential future research directions.

Prevalence of subthreshold depression and its related factors in Chinese college students: A cross-sectional study.

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

Multi-level bioinformatics resources support drug target discovery of protein-protein interactions.

Drug discovery often begins with a new target. Protein-protein interactions (PPIs) are crucial to multitudinous cellular processes and offer a promising avenue for drug-target discovery. PPIs are characterized by multi-level complexity: at the protein level, interaction networks can be used to identify potential targets, whereas at the residue level, the details of the interactions of individual PPIs can be used to examine a target's druggability. Much great progress has been made in target discovery through multi-level PPI-related computational approaches, but these resources have not been fully discussed. Here, we systematically survey bioinformatics tools for identifying and assessing potential drug targets, examining their characteristics, limitations and applications. This work will aid the integration of the broader protein-to-network context with the analysis of detailed binding mechanisms to support the discovery of drug targets.

Therapeutic future of Fuchs endothelial corneal dystrophy: An ongoing way to explore.

Fuchs endothelial corneal dystrophy (FECD) is one of the most common corneal diseases that causes loss of visual acuity in the world. FECD is a genetically and pathogenetically heterogeneous disease that results in the failure of corneal endothelial cells to maintain fluid balance and functional homeostasis of the cornea. Corneal edema, central guttae formation, and bullae development are common corneal pathologies. Currently, the mainstay of FECD treatment is surgery. However, limited sources of corneal graft and postsurgical complications remain problematic. In recent years, with advances in medical science and technology, there have been a few promising trials of new treatment modalities for FECD. In addition to new surgical methods, novel modalities can be classified into pharmacological-associated treatment, cell therapy-associated treatment, and gene therapy-associated treatment. In this article, our primary focus is on the most recent clinical trials related to FECD, and we present a stepwise approach to enhance FECD management and ultimately improve patient outcomes. We thoroughly searched for FECD clinical trials and reviewed the study designs, methodologies, and outcomes of each trial conducted within the past decade. It is imperative for physicians to stay up-to-date with these cutting-edge treatment approaches.

Small Molecules Accelerate Skin Wound Healing: Shikonin Efficacy and Mechanism of Action in Mice / Las Moléculas Pequeñas Aceleran la Curación de Heridas en la Piel: Eficacia de Shikonin y Mecanismo de Acción en Ratones

SUMMARY: The objective of this study was to investigate the therapeutic wound healing potential and molecular mechanisms of shikonin as small molecules in vitro. A mouse burn model was used to explore the potential therapeutic effect of shikonin; we traced proliferating cells in vivo to locate the active area of skin cell proliferation. Through the results of conventional pathological staining, we found that shikonin has a good effect on the treatment of burned skin and promoted the normal distribution of skin keratin at the damaged site. At the same time, shikonin also promoted the proliferation of skin cells at the damaged site; importantly, we found a significant increase in the number of fibroblasts at the damaged site treated with shikonin. Most importantly, shikonin promotes fibroblasts to repair skin wounds by regulating the PI3K/AKT signaling pathway. This study shows that shikonin can effectively promote the proliferation of skin cell, and local injection of fibroblasts in burned skin can play a certain therapeutic role.

El objetivo de este trabajo fue investigar el potencial terapéutico de cicatrización de heridas y los mecanismos moleculares de la shikonina como moléculas pequeñas in vitro. Se utilizó un modelo de quemaduras en ratones para explorar el posible efecto terapéutico de la shikonina; Rastreamos las células en proliferación in vivo para localizar el área activa de proliferación de células de la piel. A través de los resultados de la tinción para patología convencional, encontramos que la shikonina tiene un buen efecto en el tratamiento de la piel quemada y promueve la distribución normal de la queratina de la piel en el sitio dañado. Al mismo tiempo, la shikonina también promovió la proliferación de células de la piel en el sitio dañado. Es importante destacar que encontramos un aumento significativo en la cantidad de fibroblastos en el sitio dañado tratado con shikonina. Lo más importante es que la shikonina promueve la función reparadora de fibroblastos en las heridas de la piel regulando la vía de señalización PI3K/ AKT. Este estudio muestra que la shikonina puede promover eficazmente la proliferación de células de la piel y que la inyección local de fibroblastos en la piel quemada puede desempeñar un cierto papel terapéutico.

Single-Plane Retroperitoneoscopic Adrenalectomy Guided by Indocyanine Green Dye: An Optimized Step.

Background: The objective of this study was to explore the perioperative outcomes of single-plane posterior retroperitoneoscopic adrenalectomy (SPRA) guided by indocyanine green dye (ICG) fluorescence imaging. Methods: A retrospective analysis of patients who underwent SPRA from April to September 2023 in our center was conducted. Patients were divided into the ICG group and the non-ICG group, based on whether they received intraoperative ICG fluorescence guided or not. Baseline and perioperative data were recorded and analyzed by R software (R 4.3.1). Results: A total of 23 patients were enrolled in the study, with 12 in the ICG group and 11 in the non-ICG group. The demographics including age, gender, body mass index, or American Society of Anesthesiologists classification showed no significant differences between groups. There were obvious advantages in shortening adrenal gland localization time and total operative time, as well as reducing estimated blood loss in the ICG group compared with the non-ICG group (5.58 ± 0.36 minutes vs 7.55 ± 0.62 minutes, p < 0.001; 27.50 ± 5.46 minutes vs 45.00 ± 10.99 minutes, p < 0.001; 22.91 ± 7.57 mL vs 54.54 ± 18.90 mL, p < 0.001; respectively). Furthermore, patients in the ICG group exhibited significantly lower visual analog pain scale scores at 24 hours postoperatively and at discharge (p = 0.001 and p = 0.006, respectively). The oral intake intervals, hospital stays, and perioperative complications were comparable between groups. Conclusions: ICG-guided SPRA could be a safe and effective procedure for patients with adrenal tumors. This technique improves the accuracy and efficacy of adrenal gland localization and has shown benefits in perioperative outcomes. The use of ICG fluorescence guidance represents a promising clinical application.

Bladder neck contracture following transurethral surgery of prostate: a retrospective single-center study.

PURPOSE: Bladder neck contracture (BNC) is a rare but intolerant complication after transurethral surgery of prostate. The present study aims to investigate the incidence and risk factors of BNC in patients diagnosed benign prostate hyperplasia (BPH) and following transurethral resection or enucleation of the prostate (TURP/TUEP). METHODS: This retrospective study included 1008 BPH individuals who underwent transurethral surgery of the prostate between January 2017 and January 2022. Patients' demographics, medical comorbidities, urologic characteristics, perioperative parameters, and the presence of BNC were documented. Univariate and multivariate analyses were conducted to identify the risk factors. RESULTS: A total of 2% (20/1008) BPH patients developed BNC postoperatively and the median occurring time was 5.8 months. Particularly, the incidences of BNC were 4.7% and 1.3% in patients underwent Bipolar-TURP and TUEP respectively. Preoperative urinary tract infection (UTI), elevated PSA, smaller prostate volume (PV), bladder diverticulum (BD), and B-TURP were significantly associated with BNC in the univariate analysis. Further multivariate logistic regression demonstrated preoperative UTI (OR 4.04, 95% CI 2.25 to 17.42, p < 0.001), BD (OR 7.40, 95% CI 1.83 to 31.66, p < 0.001), and B-TURP (OR 3.97, 95% CI 1.55 to 10.18, p = 0.004) as independent risk factors. All BNC patients were treated with transurethral incision of the bladder neck (TUIBN) combined with local multisite injection of betamethasone. During a median follow-up of 35.8 months, 35% (7/20) of BNC patients recurred at a median time of 1.8 months. CONCLUSION: BNC was a low-frequency complication following transurethral surgery of prostate. Preoperative UTI, BD, and B-TURP were likely independent risk factors of BNC. TUIBN combined with local multisite injection of betamethasone may be promising choice for BNC treatment.

Human-virus protein-protein interactions maps assist in revealing the pathogenesis of viral infection.

Many significant viral infections have been recorded in human history, which have caused enormous negative impacts worldwide. Human-virus protein-protein interactions (PPIs) mediate viral infection and immune processes in the host. The identification, quantification, localization, and construction of human-virus PPIs maps are critical prerequisites for understanding the biophysical basis of the viral invasion process and characterising the framework for all protein functions. With the technological revolution and the introduction of artificial intelligence, the human-virus PPIs maps have been expanded rapidly in the past decade and shed light on solving complicated biomedical problems. However, there is still a lack of prospective insight into the field. In this work, we comprehensively review and compare the effectiveness, potential, and limitations of diverse approaches for constructing large-scale PPIs maps in human-virus, including experimental methods based on biophysics and biochemistry, databases of human-virus PPIs, computational methods based on artificial intelligence, and tools for visualising PPIs maps. The work aims to provide a toolbox for researchers, hoping to better assist in deciphering the relationship between humans and viruses.

Myopia: Its Status and Environmental Correlations Among School Students in Fushun, China.

Our objective was to investigate the status and influence of myopia among primary school students in Fushun, Liaoning Province, China. We aimed to provide a theoretical and epistemological basis for implementing myopia prevention initiatives. We employed cluster sampling and surveyed 5216 primary school students from grades 1-6 across eight primary schools in Fushun City. Our participants included 2606 males and 2610 females whose average age was 9.25 (SD = 1.76) years. The rate of myopia among these primary school students was 29.54%, with statistically significant differences among students of different genders and grades. Logistic regression analysis further identified several possible protective factors, including appropriate reading distance, adequate home lighting, regular breaks between classes, conscientious eye exercises, and daily outdoor physical activity. Conversely, the associated risk factors were being female, being in a higher grade level, spending more than 4 hours on homework, occasionally reading while lying down, and having one or both parents with myopia. Overall, our results indicated a high incidence of myopia, highlighting the need for scientifically controlled interventions to manage and mitigate the occurrence and progression of myopia in this population.

Tautomeric cinnamoylphloroglucinol-monoterpene adducts from Cleistocalyx operculatus and their antiviral activities.

Guided by 1H NMR spectroscopic experiments using the characteristic enol proton signals as probes, three pairs of new tautomeric cinnamoylphloroglucinol-monoterpene adducts (1-3) were isolated from the buds of Cleistocalyx operculatus. Their structures with absolute configurations were established by spectroscopic analysis, modified Mosher's method, and quantum chemical electronic circular dichroism calculation. Compounds 1-3 represent a novel class of cinnamoylphloroglucinol-monoterpene adducts featuring an unusual C-4-C-1' linkage between 2,2,4-trimethyl-cinnamyl-ß-triketone and modified linear monoterpenoid motifs. Notably, compounds 1-3 exhibited significant in vitro antiviral activity against respiratory syncytial virus (RSV).

Secoiridoid glycosides from the fruits of Ligustrum lucidum and their in vitro anti-inflammatory activity.

Seven new secoiridoid glycosides (1-7), together with a known analogue (8), were isolated from the fruits of Ligustrum lucidum. Their structures with absolute configurations were determined by HR-ESI-MS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectroscopic analysis, as well as biogenetic consideration. Compounds 1 and 2 are the first examples of secoiridoid glycoside dimers featuring a rare rearranged oleoside-type secoiridoid moiety, and compounds 3-7 represent a new class of oleoside-type secoiridoid glycosides with unusual stereochemistry at C-1 position. A plausible biosynthetic pathway for this group of unusual secoiridoid glycosides was also proposed herein. In addition, the isolates were evaluated for their in vitro anti-inflammatory activity, and all tested compounds exhibited modest inhibitory effects against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages.

Clinical characteristics, treatment, and survival of 30 patients with gastrointestinal natural killer/T-cell lymphoma.

BACKGROUND: The gastrointestinal (GI) tract is the second most frequent extranasal involvement site for ENKTL. This study aimed to explore the clinicopathological features, treatment models, survival outcomes, and prognosis of gastrointestinal ENKTL (GI-ENKTL). METHODS: The clinical data of GI-ENKTL patients were extracted from the China Lymphoma Collaborative Group (CLCG) database and were analyzed retrospectively. RESULTS: A total of 30 patients were enrolled, with a male/female ratio of 4:1 and a median age of 42 years. Twenty-nine patients received chemotherapy, of whom 15 patients received asparaginase-based (ASP-based) regimens. Moreover, seven received surgery and three received radiotherapy. The overall response an d complete remission rates were 50.0% and 30.0% for the whole cohort, 50.0% and 37.5% for patients treated with ASP-based regimens, and 50.0% and 25.0% for those treated with non-ASP-based regimens, respectively. The median follow-up was 12.9 months and the 1-year overall survival rate was 40.0% for the whole cohort. For those patients in an early stage, ASP-based regimens resulted in a superior 1-year progression-free survival rate compared to non-ASP-based regimens (100.0% vs. 36.0%, p = .07). However, ASP-based regimens did not improve survival in patients at an advanced stage. CONCLUSION: GI-ENKTL still has a poor prognosis, even in the era of modern asparaginase-based treatment strategies.