Future Interventions Research Articles

Exploring the Common Pathogenic Mechanisms of Psoriasis and Atopic Dermatitis: The Interaction between SGK1 and TIGIT Signaling Pathways.

This study aims to explore the common pathogenic mechanisms of psoriasis and atopic dermatitis, two T-cell-mediated autoimmune diseases. Utilizing single-cell transcriptomic sequencing data, we revealed that Treg cells primarily express TIGIT in both psoriasis and atopic dermatitis, and identified a subset of macrophages that highly express SGK1. These cells can interact with T cells via the NECTIN2-TIGIT signaling pathway, inhibiting the differentiation of T cells into a pro-inflammatory phenotype, thereby uncovering a common immunoregulatory mechanism in both diseases. Furthermore, we discovered that inhibition of SGK1 exacerbates the inflammatory response in disease models of both conditions. These findings not only provide a new perspective for a common therapeutic strategy for psoriasis and atopic dermatitis but also highlight the importance of considering these molecular interactions in future treatments. Validation of these observations through further qPCR, immunofluorescence, and animal studies has identified potential new targets for the treatment of psoriasis and atopic dermatitis.

Current findings on the antitumor effects of metformin on esophageal squamous cell carcinoma (Review).

Esophageal squamous cell carcinoma (ESCC) is an intractable type of cancer that requires novel therapeutic modalities, since the therapeutic outcomes are often inadequate, even in response to multidisciplinary treatment. The antitumor effect of metformin, an antidiabetic drug, has been reported in esophageal cancer; however, its effects are diverse. Since various multidisciplinary therapies are used in ESCC, the antitumor effect of metformin is expected to be synergistic in some treatment strategies. The present review summarizes the antitumor effects of metformin and discusses its use in combination with existing therapies. The present study reviewed relevant studies where the molecular targets of metformin (AMPK and inflammatory system signals) were described, followed by the classification and organization of its antitumor effects, and subsequently summarized the current research on its antitumor effects, especially in ESCC. A number of studies have reported that metformin prevents the development of ESCC and exerts its antitumor effects through various pathways. In addition, metformin has been shown to inhibit tumor growth, induce apoptosis, inhibit cancer cell invasion, migration and angiogenesis into the tumor, and decrease tumor malignancy, such as metastasis. Furthermore, it may modulate host tumor immunity in a tumor-suppressive manner and is expected to improve prognosis following treatment for ESCC. Notably, metformin may be beneficial in combination with chemotherapy, such as cisplatin, and radiation. By contrast, it has been shown to potentially induce resistance to 5-fluorouracil. Finally, the effects of metformin in combination with other therapies are discussed in the present study, and perspectives on the potential benefits of metformin for future ESCC treatment are presented. In conclusion, the present review may be useful in improving the understanding of the wide range of antitumor effects of metformin. Although some concerning points remain, using metformin in ESCC treatment could be promising. Notably, more knowledge needs to be accumulated regarding the effects of metformin on ESCC.

Causal role of immune cells in asthma: a Mendelian randomization study.

BackgroundImmune cells may have a significant role in the pathophysiology of asthma, according to increasing evidence, although it is yet unclear how immune cells cause asthma. Therefore, we aimed to use Mendelian randomization (MR) methods to investigate this causal relationship.Methods：This study explored the causal effects between immune cells and asthma using a two-sample Mendelian randomization technique. Using publicly available genetic data, the causal connection between asthma risk and 731 immune cell phenotypes was investigated. Sensitivity analysis guaranteed the results' stability. To further evaluate the existence of reverse causality, we employed reverse MR analysis.Results：According to the inverse-variance weighted (IVW) method, five immune cell phenotypes were found to be statistically significantly associated with asthma risk (p < 0.001). Among them, TCRgd %T cell (OR = 0.968,95%CI = 0.951-0.986), TCRgd %lymphocyte (OR = 0.978,95%CI = 0.965-0.991), HLA DR + NK AC (OR = 0.966,95% CI = 0.947-0.986) and CD3 on CD4 Treg (OR = 0.956,95%CI= 0.931-0.981), four phenotypes that resulted in a decreased risk of asthma.CD25 on transitional (OR = 1.033, 95%CI = 1.014-1.052) resulted in an increased risk of asthma. Reverse MR analysis revealed that asthma increases HLA DR + NK AC levels (p < 0.05).Conclusion：The results of MR analysis showed a causal relationship between immune cell phenotype and asthma risk, which provides a direction for future asthma treatment.

Perioperative anaphylaxis: updates on pathophysiology.

Perioperative anaphylaxis has historically been attributed to IgE/FcεRI-mediated reactions; there is now recognition of allergic and nonallergic triggers encompassing various reactions beyond IgE-mediated responses. This review aims to present recent advancements in knowledge regarding the mechanisms and pathophysiology of perioperative anaphylaxis. Emerging evidence highlights the role of the mast-cell related G-coupled protein receptor X2 pathway in direct mast cell degranulation, shedding light on previously unknown mechanisms. This pathway, alongside traditional IgE/FcεRI-mediated reactions, contributes to the complex nature of anaphylactic reactions. Investigations into the microbiota-anaphylaxis connection are ongoing, with potential implications for future treatment strategies. While serum tryptase levels serve as mast cell activation indicators, identifying triggers remains challenging. A range of mediators have been associated with anaphylaxis, including vasoactive peptides, proteases, lipid molecules, cytokines, chemokines, interleukins, complement components, and coagulation factors. Further understanding of clinical endotypes and the microenvironment where anaphylactic reactions unfold is essential for standardizing mediator testing and characterization in perioperative anaphylaxis. Ongoing research aims to elucidate the mechanisms, pathways, and mediators involved across multiple organ systems, including the cardiovascular, respiratory, and integumentary systems, which will be crucial for improving patient outcomes.

Crystal structure of glycerol kinase from Trypanosoma cruzi, a potential molecular target in Chagas disease.

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. It bears a significant global health burden with limited treatment options, thus calling for the development of new and effective drugs. Certain trypanosomal metabolic enzymes have been suggested to be druggable and valid for subsequent inhibition. In this study, the crystal structure of glycerol kinase from T. cruzi, a key enzyme in glycerol metabolism in this parasite, is presented. Structural analysis allowed a detailed description of the glycerol binding pocket, while comparative assessment pinpointed a potential regulatory site which may serve as a target for selective inhibition. These findings advance the understanding of glycerol metabolism in eukaryotes and provide a solid basis for the future treatment of Chagas disease.

Innovative Statistical Model Uncover Effective Herbal Medicines Among Personalized Treatment Plans in Persian Medicine: A Small-Scale Study in Type 2 Diabetes.

Objectives: In holistic medicine, developing personalized treatment plans is challenging due to the multitude of possible therapy combinations. This study introduces the use of a statistical approach to identify the most effective herbal medicines prescribed in Persian medicine (PM) in a small-scale sample of patients with type 2 diabetes mellitus (T2DM). Methods: This prospective observational cohort study was conducted with 47 patients with T2DM referred to Behesht Clinic in Tehran, Iran. A physician prescribed individualized PM treatment for T2DM and related systemic issues. The fasting blood sugar (FBS) level of each patient was recorded at initial and two follow-up visits, with visit intervals and treatment modifications determined by patient health status. Patients who completed two follow-up visits were included in the final analysis (n = 27). Data were analyzed using R software. A general linear model was assumed for the mean response, along with an exponential covariance pattern model, to manage irregularly timed measurements. Results: Two fitted models showed that, after adjusting for confounders, the use of the "Diabetes Capsule" significantly reduced the average FBS by 17.14 mmol/L (p = 0.046). For each unit increase in the consumption of "Diabetes Capsule" or "Hab-e-Amber Momiai," the average FBS decreased by 15.22 mmol/L (p = 0.015) and 14.14 mmol/L (p = 0.047), respectively. Conclusion: It is possible to observe which medications are most effective, even when treatments are applied in a holistic and personalized fashion. Preliminary studies such as these may identify promising products for testing in clinical trials conducted under standardized conditions, to inform initial choices for future personalized treatments.

Carbon - 12C ion radiation-induced cell death and molecular mechanisms in malignant cells: Evidence from in vivo and in vitro

Conventional radiotherapy has been revolutionized for several decades. Recently, the delivery of high linear energy transfer (LET) radiation such as heavy carbon ion therapy has gained more attention. Among all low-energy therapies such as photon, X-ray, and gamma radiation therapy, 12C heavy carbon ion therapy is the best therapy for cancer treatment due to its high relative biological effectiveness (RBE). It has been studied that many tumors show resistance to chemotherapy and low energy transfer radiation. The unique nature of high LET shows unique Bragg peaks where very little radiation are applied on the tumor cells and better results can be achieved. It effectively kills the tumor cells without affecting the normal cells. There are some limitations to conventional radiotherapy. Radiotherapy with the low LET group may not work properly. Carbon ion radiation (CIR) induces malignant cell death in different modes, such as apoptosis, senescence, autophagy, immunogenic cell death and necrosis. Heavy carbon ion therapy enhances cell death by altering different molecular signalling pathways such as p53, AKT, MEK, caspase and STAT–3. Investigation of the major molecular cell death by carbon ion irradiation is very essential to understand the modalities of heavy carbon ion induced cell death. In this context, the investigation of different signaling cascades may open new horizons in cancer treatment. The therapeutic efficacy and application of heavy carbon ion beams along with some molecular inhibitors, radio sensitizers, and gene therapy would be helpful for future cancer treatment. Therefore, a more thorough investigation in this field is needed. The current review article highlights the recent advances in cancer therapy research based on Carbon 12C Ion radiation-induced cell death.

Controllable Construction of Aptamer-Modified Fe3O4@SiO2-Au Core-Shell-Satellite Nanocomposites with Surface-Enhanced Raman Scattering and Photothermal Properties and Their Effective Capture, Detection, and Elimination of Staphylococcus aureus

The early monitoring and inactivation of bacteria are of crucial importance in preventing the further spread of foodborne pathogens. Staphylococcus aureus (S. aureus), a prototypical foodborne pathogen, is widely present in the natural environment and has the capability to trigger a range of diseases at low concentrations. In this work, we designed Fe3O4@SiO2-Au core–shell–satellite nanocomposites (NCs) modified with aptamer for efficient capture, high-sensitivity surface-enhanced Raman scattering (SERS) detection, and photothermal therapy (PTT) against S. aureus. Fe3O4@SiO2-Au NCs with tunable Au nanocrystal nanogaps were prepared. By combining the finite-difference time-domain (FDTD) method and experimental results, we studied the electric field distribution of Fe3O4@SiO2-Au under different Au nanogaps and ultimately obtained the optimal SERS substrate FSA-60. The modification of aptamer on the surfaces of FSA-60 could be used for the specific capture and selective detection of S. aureus, achieving a detection limit of as low as 50 cfu/mL. Furthermore, Apt-FSA-60 possessed excellent photothermal properties, demonstrating the strong photothermal killing ability against S. aureus. Therefore, Apt-FSA-60 is a promising high-sensitivity SERS substrate and efficient photothermal agent and is expected to be widely applied and promoted in future disease prevention and treatment.

Autoantibodies to joint-related peptides as predictive markers in early rheumatoid arthritis.

For better management of rheumatoid arthritis (RA), new biomarkers are needed to predict the development of different disease courses. This study aims to identify autoantibodies against epitopes on proteins in the joints and to predict disease outcome in patients with new onset RA. Sera from new onset RA patients from the Swedish BARFOT and TIRA-2 cohorts (n = 1986) were screened for autoantibodies to selected peptides (JointIDs) in a bead-based multiplex flow immunoassay. Disease outcomes included Boolean remission 1.0, swollen joint count and radiographic destruction. Multivariate logistic regression and zero-inflated negative binomial models that accounted for clinical factors were used to identify JointIDs with the strongest potential to predict prognosis. Boolean remission was predicted with 42% sensitivity and 75% specificity in male patients positive for antibodies to a non-modified collagen type II (COL2) peptide at 12 months. When antibodies to a specific citrullinated cartilage oligomeric protein (COMP) peptide were absent and the patient was in Boolean remission at 6 months, the sensitivity was 13% and the specificity 99%. Positivity for the non-modified COL2 peptide also reduced the frequency of swollen joints by 41% and 33% at 6 and 12 months, respectively. Antibodies to cyclic citrullinated peptides (aCCP) predicted joint destruction with low specificity (58%). Positivity for a COL2 and a glucose-6-phosphate dehydrogenase peptide in citrullinated forms increased specificity (86%) at the expense of sensitivity (39%). Autoantibodies against joint-related proteins at RA diagnosis predict remission with high specificity and, in combination with clinical factors, may guide future treatment decisions.

Treacher Collins syndrome: current and emerging treatment options

Treacher Collins syndrome is a rare congenital disorder characterized by bilateral craniofacial malformations, including mandibular and zygomatic hypoplasia, cleft palate, and eye anomalies, resulting in significant variability in symptom severity. The syndrome, with an incidence of approximately 1 in 50,000 births, is primarily caused by mutations in the TCOF1 gene and less frequently by mutations in POLR1C and POLR1D genes, disrupting ribosome biogenesis crucial for craniofacial development. Clinical manifestations encompass diverse craniofacial, auditory, and skeletal abnormalities, often leading to airway complications and hearing loss. Management involves a multidisciplinary approach, combining surgical interventions such as mandibular distraction osteogenesis and orthognathic surgeries with advanced imaging techniques for precise planning. Hearing loss is managed with bone conduction aids and cochlear implants, although outcomes may vary due to associated anomalies. Genetic testing aids in diagnosis and family planning decisions, while emerging therapies like genome editing and regenerative medicine show promise for future treatments. Despite challenges in long-term management and relapse rates in surgical corrections, ongoing research aims to enhance therapeutic efficacy and patient outcomes, emphasizing the need for tailored treatment strategies addressing both functional and aesthetic aspects.

Dissecting the Impact of Maternal Androgen Exposure on Developmental Programming through Targeting the Androgen Receptor.

Women with polycystic ovary syndrome (PCOS) exhibit sustained elevation in circulating androgens during pregnancy, an independent risk factor linked to pregnancy complications and adverse outcomes in offspring. Yet, further studies are required to understand the effects of elevated androgens on cell type-specific placental dysfunction and fetal development. Therefore, a PCOS-like mouse model induced by continuous androgen exposure is examined. The PCOS-mice exhibited impaired placental and embryonic development, resulting in mid-gestation lethality. Co-treatment with the androgen receptor blocker, flutamide, prevents these phenotypes including germ cell specification . Comprehensive profiling of the placenta by whole-genome bisulfite and RNA sequencing shows a reduced proportion of trophoblast precursors, possibly due to the downregulation of Cdx2 expression. Reduced expression of Gcm1, Synb, and Prl3b1 is associated with reduced syncytiotrophoblasts and sinusoidal trophoblast giant cells, impairs placental labyrinth formation. Importantly, human trophoblast organoids exposed to androgens exhibit analogous changes, showing impaired trophoblast differentiation as a key feature in PCOS-related pregnancy complications. These findings provide new insights into the potential cellular targets for future treatments.

Sex-Dependent T Cell Dysregulation in Mice with Diet-Induced Obesity

Obesity is an emerging public health problem. Chronic low-grade inflammation is considered a major promotor of obesity-induced secondary diseases such as cardiovascular and fatty liver disease, type 2 diabetes mellitus, and several cancer entities. Most preliminary studies on obesity-induced immune responses have been conducted in male rodents. Sex-specific differences between men and women in obesity-induced immune dysregulation have not yet been fully outlined but are highly relevant to optimizing prevention strategies for overweight-associated complications. In this study, we fed C57BL/6 female vs. male mice with either standard chow or an obesity-inducing diet (OD). Blood and spleen immune cells were isolated and analyzed by flow cytometry. Lean control mice showed no sex bias in systemic and splenic immune cell composition, whereas the immune responses to obesity were significantly distinct between female and male mice. While immune cell alterations in male OD mice were characterized by a significant reduction in T cells and an increase in myeloid-derived suppressor cells (MDSC), female OD mice displayed preserved T cell numbers. The sex-dependent differences in obesity-induced T cell dysregulation were associated with varying susceptibility to body weight gain and fatty liver disease: Male mice showed significantly more hepatic inflammation and histopathological stigmata of fatty liver in comparison to female OD mice. Our findings indicate that sex impacts susceptibility to obesity-induced T cell dysregulation, which might explain sex-dependent different incidences in the development of obesity-associated secondary diseases. These results provide novel insights into the understanding of obesity-induced chronic inflammation from a sex-specific perspective. Given that most nutrition, exercise, and therapeutic recommendations for the prevention of obesity-associated comorbidities do not differentiate between men and women, the data of this study are clinically relevant and should be taken into consideration in future trials and treatment strategies.

The Role of the Gut and Airway Microbiota in Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review

In recent years, there has been growing interest in understanding the potential role of microbiota dysbiosis or alterations in the composition and function of human microbiota in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). This systematic review evaluated the literature on CRSwNP and host microbiota for the last ten years, including mainly nasal bacteria, viruses, and fungi, following the PRISMA guidelines and using the major scientific publication databases. Seventy original papers, mainly from Asia and Europe, met the inclusion criteria, providing a comprehensive overview of the microbiota composition in CRSwNP patients and its implications for inflammatory processes in nasal polyps. This review also explores the potential impact of microbiota-modulating therapies for the CRSwNP treatment. Despite variability in study populations and methodologies, findings suggest that fluctuations in specific taxa abundance and reduced bacterial diversity can be accepted as critical factors influencing the onset or severity of CRSwNP. These microbiota alterations appear to be implicated in triggering cell-mediated immune responses, cytokine cascade changes, and defects in the epithelial barrier. Although further human studies are required, microbiota-modulating strategies could become integral to future combined CRSwNP treatments, complementing current therapies that mainly target inflammatory mediators and potentially improving patient outcomes.

Primary lateral sclerosis associated with PSEN1 Pro284Leu variant in a Colombian family: Clinical and neuropathological features.

This study investigates primary lateral sclerosis (PLS) as a rare manifestation of the presenilin 1 (PSEN1) NM_000021 c.851C>T p.Pro284Leu variant in three siblings of a Colombian family, outlining its clinical and neuropathological features and their relationship to Alzheimer's disease (AD). Data were gathered using clinical evaluations, next-generation genetic sequencing, magnetic resonance imaging, biomarker analysis, and neuropathological examination. Carriers of the PSEN1 Pro284Leu variant exhibited classic PLS symptoms, including unilateral onset and bulbar syndromes, along with cognitive decline. Neuropathology showed corticospinal tract degeneration without amyloid beta deposition in spinal white matter. Our findings suggest an overlap between PLS and AD pathology in PSEN1 variant carriers. Results support considering PLS when diagnosing AD-related motor syndromes and including PSEN1 evaluation when performing genetic testing for PLS. The study highlights the need for further research to clarify the PLS-AD relationship, informing future treatments and clinical trials. Pathogenic variants in presenilin 1 (PSEN1) can manifest as hereditary primary lateral sclerosis PSEN1 Pro284Leu carriers present motor, cognitive, and behavioral alterations Cases had corticospinal tract microgliosis and severe Aβ pathology in motor cortex There was no evidence of amyloid deposition in the spinal cord white matter All the neuropathology images are available for online visualization Myelin pallor in the spinal cord is confined to the lateral corticospinal tracts.

Antibodies targeting the tumor necrosis factor (TNF) -like ligand 1A (TL1A) in Inflammatory Bowel Disease - a new kid on the (biologics) block?

The treatment options for Inflammatory Bowel Disease (IBD) have grown over the last years. However, a significant fraction of patients either does not respond to their treatment or looses response over time. Future treatment options could include antibodies that target the tumor necrosis factor (TNF) - like ligand 1A (TL1A). TL1A is a key cytokine involved in the pathogenesis of a variety of autoimmune diseases, including IBD. Studies have shown that IBD disease severity correlates well with serum levels of TL1A. Phase 2 data from two agents currently in clinical testing have been released. In line with requirements for modern therapeutics companion diagnostic was part of these trials. This aims to identify those patients that are more likely to respond to the agents tested. With regard to the available data the risk/benefit profile seems to be promising. This article gives a short update and overview where we are at this point in time with antibodies targeting the TL1A protein in IBD.

Poor therapeutic outcomes in KRAS-mutant non-small cell lung cancer due to chemoresistance conferred by SLC7A11.

This study aimed to confirm whether Kirsten rat sarcoma viral oncogene (KRAS) mutations affect the therapeutic efficacy of non-small cell lung cancer (NSCLC) and, if so, to explore what the possible mechanisms might be. We retrospectively analyzed the efficacy of immunochemotherapy in KRAS-mutant NSCLC patients compared to driver-negative patients. Online data platforms were used to find immunotherapy cases, and survival analysis compared treatments' efficacy. Cytotoxicity assays measured chemosensitivity in KRAS-mutant versus wild-type NSCLC to drugs like paclitaxel, carboplatin, and pemetrexed. Bioinformatics confirmed the KRAS-SLC7A11 link and cell experiments tested SLC7A11's role in chemoresistance. Animal studies verified the antitumor effects of SLC7A11 inhibitors with chemotherapy. Patients with KRAS-mutated NSCLC have a shorter therapeutic effectiveness duration with immunochemotherapy than patients with driver gene-negative status. The efficacy of immunotherapy alone is similar between the two groups. The KRAS mutation can enhance chemoresistance by upregulating SLC7A11, and inhibiting SLC7A11 can increase the sensitivity of KRAS-mutated NSCLC to chemotherapy. This study suggests that KRAS-mutant NSCLC can enhance its acquired chemoresistance by overexpressing SLC7A11, leading to poorer therapeutic outcomes. Targeting the KRAS-SLC7A11 axis could increase sensitivity to chemotherapeutic drugs, providing theoretical support for future treatment directions.

Association between Interleukin-6 and Multiple Acute Infarctions in Symptomatic Intracranial Atherosclerotic Disease.

Interleukin-6 (IL-6) plays an important role in the pathophysiology of atherosclerosis. This study aimed to determine whether IL-6 is a crucial biomarker associated with Multiple Acute Infarctions (MAIs), which indicate an important stroke mechanism of artery-- to-artery embolism with a high risk of stroke recurrence in symptomatic Intracranial Atherosclerotic Disease (sICAD). We tested the association between circulating IL-6 levels and the presence of MAIs in a prospective population-based registry. We included 1,919 patients with sICAD and baseline IL-6 levels from the Third China National Stroke Registry for the current analysis, The baseline IL-6 was centrally measured at Beijing Tiantan Hospital, Images of the brain parenchyma and vascular structures were digitized and then blindly and independently read by two groups of trained readers, The recruited patients were divided into 3 groups according to IL-6 tertiles, The relationship between baseline IL-6 tertile levels and the presence of MAIs was modeled using multivariate logistic regression. Compared to patients in the first IL-6 tertile those in the second and third tertiles demonstrated a significantly higher proportion of MAIs. The odds ratios were 1.81 [95% Confidence Interval (CI), 1.42-2.30] for the second versus first tertile and 2.15 (95% CI 1.66-2.79) for the third versus first tertile, The proportion of patients with MAIs increased with rising IL-6 tertiles observed at 59.3%, 71.6% and 76.4% for the first, second and third tertiles, respectively (P for trend < 0.001). The association between higher IL-6 tertiles and increased proportion of MAIs was also present in subgroups defined by age < 65 years, age ≥ 65 years, male, and high-sensitivity C-reactive Protein (hs-CRP) ≥ 2 mg/L. Furthermore, a significant interaction was detected for the hs- CRP subgroup (P = 0.038). In sensitivity analyses, the positive correlation between IL-6 levels and the proportion of MAIs remained consistent. In patients with sICAD, higher IL-6 levels were associated with an increased proportion of MAIs. IL-6 could be used as a biomarker and a potential therapeutic target for future atherosclerosis treatment and prevention in patients with sICAD.

Machine learning-enabled prediction of prolonged length of stay in hospital after surgery for tuberculosis spondylitis patients with unbalanced data: a novel approach using explainable artificial intelligence (XAI)

BackgroundTuberculosis spondylitis (TS), commonly known as Pott’s disease, is a severe type of skeletal tuberculosis that typically requires surgical treatment. However, this treatment option has led to an increase in healthcare costs due to prolonged hospital stays (PLOS). Therefore, identifying risk factors associated with extended PLOS is necessary. In this research, we intended to develop an interpretable machine learning model that could predict extended PLOS, which can provide valuable insights for treatments and a web-based application was implemented.MethodsWe obtained patient data from the spine surgery department at our hospital. Extended postoperative length of stay (PLOS) refers to a hospitalization duration equal to or exceeding the 75th percentile following spine surgery. To identify relevant variables, we employed several approaches, such as the least absolute shrinkage and selection operator (LASSO), recursive feature elimination (RFE) based on support vector machine classification (SVC), correlation analysis, and permutation importance value. Several models using implemented and some of them are ensembled using soft voting techniques. Models were constructed using grid search with nested cross-validation. The performance of each algorithm was assessed through various metrics, including the AUC value (area under the curve of receiver operating characteristics) and the Brier Score. Model interpretation involved utilizing methods such as Shapley additive explanations (SHAP), the Gini Impurity Index, permutation importance, and local interpretable model-agnostic explanations (LIME). Furthermore, to facilitate the practical application of the model, a web-based interface was developed and deployed.ResultsThe study included a cohort of 580 patients and 11 features include (CRP, transfusions, infusion volume, blood loss, X-ray bone bridge, X-ray osteophyte, CT-vertebral destruction, CT-paravertebral abscess, MRI-paravertebral abscess, MRI-epidural abscess, postoperative drainage) were selected. Most of the classifiers showed better performance, where the XGBoost model has a higher AUC value (0.86) and lower Brier Score (0.126). The XGBoost model was chosen as the optimal model. The results obtained from the calibration and decision curve analysis (DCA) plots demonstrate that XGBoost has achieved promising performance. After conducting tenfold cross-validation, the XGBoost model demonstrated a mean AUC of 0.85 ± 0.09. SHAP and LIME were used to display the variables’ contributions to the predicted value. The stacked bar plots indicated that infusion volume was the primary contributor, as determined by Gini, permutation importance (PFI), and the LIME algorithm.ConclusionsOur methods not only effectively predicted extended PLOS but also identified risk factors that can be utilized for future treatments. The XGBoost model developed in this study is easily accessible through the deployed web application and can aid in clinical research.

Cortical tagged synaptic long-term depression in the anterior cingulate cortex of adult mice.

The anterior cingulate cortex (ACC) is a key cortical region for pain perception and emotion. Different forms of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), have been reported in the ACC. Synaptic tagging of LTP plays an important role in hippocampus-related associative memory. In this study, we demonstrate that synaptic tagging of LTD is detected in the ACC of adult male and female mice. This form of tagged LTD requires the activation of metabotropic glutamate receptor subtype 1 (mGluR1). The induction of tagged LTD is time-related with the strongest tagged LTD appearing when the interval between two independent stimuli is 30 min. Inhibitors of mGluR1 blocked the induction of tagged LTD, however, blocking N-methyl-d-aspartate (NMDA) receptors did not affect the induction of tagged LTD. Nimodipine, an inhibitor of L-type voltage-gated calcium channels (VGCCs), also blocked tagged LTD. In an animal model of amputation, we found that tagged LTD was either reduced or completely blocked. Together with our previous report of tagged LTP in the ACC, this study strongly suggests that excitatory synapses in the adult ACC are highly plastic. The biphasic tagging of synaptic transmission provides a new form of heterosynaptic plasticity in the ACC which has functional and pathophysiological significance in phantom pain.Significance Statement The anterior cingulate cortex (ACC) is a key cortical region for pain perception and chronic pain. Previous studies have reported a novel form of long-term heterosynaptic potentiation in the ACC. In this study, we discovered a long-term depression (LTD) form of synaptic tagging in the ACC of adult male and female mice. This form of tagged LTD requires the activation of metabotropic glutamate receptors (mGluRs). In an animal model of amputation, tagged LTD is reduced or completely blocked. Our results strongly suggest that brain cortices of adult mice are highly plastic and show biphasic tagging of plasticity. These findings of tagged LTD may provide a new direction for future treatment of phantom pain and amputation-related emotional disorders.

The interplay between borderline personality disorder and oxytocin: a systematic narrative review on possible contribution and treatment options

BackgroundBorderline personality disorder (BPD) is a complex mental health condition marked by instability in mood, relationships, self-image, and behavior. Individuals with BPD often struggle with intense emotions, impulsivity, and maintaining stable relationships. Oxytocin, known as the "love hormone" or "bonding hormone," plays a crucial role in social bonding, trust, empathy, and emotional regulation and its dysregulation may contribute to BPD difficulties. This systematic review aims to analyze existing literature, examining the intricate interplay and encouraging future research and treatment strategies.MethodsA systematic search of Literature in PubMed, Embase and Psychinfo, without any language or time restriction, was performed until March 2024 combining thesaurus and free-search indexing terms related to “borderline personality disorder” and “oxytocin”, producing 310 results (77 in PubMed, 166 in Embase and 67 in Psychinfo). Ninety-four full texts were analyzed, and 70 articles were included in qualitative analysis.ResultsOxytocin may influence attachment styles, parental behaviors, and stress responses, particularly in individuals with a history of childhood trauma. The interaction between oxytocin, genetics, early life experiences, and environmental factors contributes to the complexity of BPD. Genetic variations in the oxytocin receptor gene may influence social and emotional abilities and contribute to the development of psychopathology. Additionally, early adverse experiences, such as childhood maltreatment, can alter oxytocin functioning, impacting social cognition and emotional regulation.However, oxytocin's role in BPD treatment remains uncertain, with some studies suggesting potential benefits for specific symptoms like social threat avoidance, while others indicate adverse effects on nonverbal behavior and mentalizing.ConclusionUnderstanding oxytocin's role in BPD offers insights into potential therapeutic interventions. While oxytocin-based treatments may hold promise for addressing specific symptoms, further research is needed.