Angiogenesis-related lncRNAs index: A predictor for CESC prognosis, immunotherapy efficacy, and chemosensitivity.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is a common gynecologic tumor and patients with advanced and recurrent disease usually have a poor clinical outcome. Angiogenesis is involved in the biological processes of tumors and can promote tumor growth and invasion. In this paper, we created a signature for predicting prognosis based on angiogenesis-related lncRNAs (ARLs). This provides a prospective direction for enhancing the efficacy of immunotherapy in CESC patients. We screened seven OS-related ARLs by univariate and multivariate regression analyses and Lasso analysis and developed a prognostic signature at the same time. Then, we performed an internal validation in the TCGA-CESC cohort to increase the precision of the study. In addition, we performed a series of analyses based on ARLs, including immune cell infiltration, immune function, immune checkpoint, tumor mutation load, and drug sensitivity analysis. Our created signature based on ARLs can effectively predict the prognosis of CESC patients. To strengthen the prediction accuracy of the signature, we built a nomogram by combining signature and clinical features.

Proton Pump Inhibitor Use and Bone Health in Patients With Rheumatic Diseases: A Cross-Sectional Study.

OBJECTIVE: To assess the effect of proton pump inhibitor (PPI) use on bone mineral density (BMD) and bone microarchitecture as measured by the trabecular bone score (TBS) in patients with inflammatory rheumatic and musculoskeletal diseases (iRMDs). METHODS: Cross-sectional data from a prospective single-center cohort (2015 to 2022) of patients with iRMDs were used to evaluate 3 co-primary outcomes: BMD of the left femoral neck and the lumbar spine (as T-scores) and the TBS. Inverse probability weighting adjusted for numerous confounders including age, sex, body mass index, current and cumulative glucocorticoid (GC) dose, C-reactive protein levels, disability, and others. Analyses were based on general linear models, following a prespecified statistical analysis plan. RESULTS: The study included 1495 patients (75% women; mean age, 62.6±13.1 years; 49% and 63% with regular PPI and GC use, respectively). The PPI users had lower BMD at both spine (adjusted contrast -0.25; 95% CI, -0.47 to -0.04; P=.02) and femoral neck (-0.17 [-0.35 to 0.01]; P=.07). Differences between PPI users and nonusers were statistically significant only in patients concurrently using GCs at more than 7.5 mg/d prednisone equivalent. The TBS was similar in PPI users and nonusers (adjusted contrast, 0.00 [-0.04 to 0.04]; P=.97). CONCLUSION: Our results suggest that PPIs lead to a loss of BMD rather than an impairment of bone microarchitecture in patients with iRMDs. The negative association between PPI use and BMD appears to be dependent on concurrent GC use. Clinicians should carefully review the indication for PPI use in patients with iRMDs, especially in those receiving higher dose GCs.

Nutritional aspects in autoimmune diseases undergoing hematopoietic stem cell transplantation: overview and recommendations on behalf of the EBMT ADWP and Nurses Group.

Autoimmune diseases (ADs) represent a heterogeneous group of conditions affecting 5-10% of the global population. In recent decades, hematopoietic stem cell transplant (HSCT), mainly autologous, has been successfully adopted to treat patients affected by severe/refractory ADs. In this context malnutrition has a detrimental impact on relapse, mortality, infection rate, engraftment, long-term survival, and prolongation of hospitalization. However, in this population, the management of nutrition should be improved since nutritional assessment is partially performed in routine clinical practice. A panel of nurses and physicians from the European Society for Blood and Marrow Transplantation (EBMT) reviewed all available evidence based on current literature and expert practices from centers with extensive experience in HSCT for ADs, on the nutritional management of ADs patients during HSCT procedure. In this context, adequate nutritional status predicts a better response to treatment and improves quality of life. Herein, a systematic and comprehensive monitoring of nutritional status before, during and after HSCT, with adequate nutritional support in the case of ADs patients, in addition to assessing the dietary requirements associated with HSCT has been covered. Moreover, given the singularity of each AD, the underlying disease should be considered for an appropriate approach. The management and evaluation of nutritional status must be carried out by a multidisciplinary team to assess the needs, monitor the effectiveness of each intervention, and prevent complications, especially in complex situations as patients affected by ADs.

ERLIN1/2 scaffolds bridge TMUB1 and RNF170 and restrict cholesterol esterification to regulate the secretory pathway.

Complexes of ERLIN1 and ERLIN2 (ER lipid raft-associated 1 and 2) form large ring-like cup-shaped structures on the endoplasmic reticulum (ER) membrane and serve as platforms to bind cholesterol and E3 ubiquitin ligases, potentially defining functional nanodomains. Here, we show that ERLIN scaffolds mediate the interaction between the full-length isoform of TMUB1 (transmembrane and ubiquitin-like domain-containing 1) and RNF170 (RING finger protein 170). We identify a luminal N-terminal conserved region in TMUB1 and RNF170, which is required for this interaction. Three-dimensional modelling shows that this conserved motif binds the stomatin/prohibitin/flotillin/HflKC domain of two adjacent ERLIN subunits at different interfaces. Protein variants that preclude these interactions have been previously linked to hereditary spastic paraplegia. Using omics-based approaches in combination with phenotypic characterization of HeLa cells lacking both ERLINs, we demonstrate a role of ERLIN scaffolds in limiting cholesterol esterification, thereby favouring cholesterol transport from the ER to the Golgi apparatus and regulating Golgi morphology and the secretory pathway.

[Current data on rheumatological care: annual report from the National database (NDB) of the regional collaborative arthritis centres in Germany]. / Aktuelle Zahlen zur rheumatologischen Versorgung ­ Jahresbericht aus der Kerndokumentation der regionalen kooperativen Rheumazentren.

In the National database (NDB) of the German regional collaborative arthritis centres, annual data on the rheumatological care of patients with inflammatory rheumatic diseases have been collected since 1993. This first annual report presents current cross-sectional data on medication and patient-reported outcomes gathered in 2022.

A Case Report of Malignant Perivascular Epithelioid Cell Tumors of the Uterus and Literature Review.

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors originating from perivascular epithelioid cells. In gynecological system, the uterus is one of the most common sites affected by PEComas. Most PEComas are benign, and patients usually have a good prognosis. However, malignant uterus PEComa is rare, and better comprehensive epidemiological investigations are needed. To date, there are a few reported cases of uterus PEComa. We herein report a rare case of malignant PEComa occurred in the uterine corpus and cervix, possibly accompanied by pulmonary lymphangioleiomyomatosis (PLAM). In addition, 55 cases of malignant uterus PEComa were picked out and collected in the data base of PubMed and Medline. On the one hand, the age of onset, population distribution, clinical manifestations, metastatic sites and routes of metastasis were analysed. On the other hand, a summary of the epidemiology, pathogenesis, diagnosis, and treatments of uterus PEComa was given.

Exploring volumetric abnormalities in subcortical L-HPA axis structures in pediatric generalized anxiety disorder.

BACKGROUND: Pediatric generalized anxiety disorder (GAD) is debilitating and increasingly prevalent, yet its etiology remains unclear. Some believe the disorder to be propagated by chronic dysregulation of the limbic-hypothalamic-pituitary-adrenal (L-HPA) axis, but morphometric studies of implicated subcortical areas have been largely inconclusive. Recognizing that certain subcortical subdivisions are more directly involved in L-HPA axis functioning, this study aims to detect specific abnormalities in these critical areas. METHODS: Thirty-eight MRI scans of preschool children with (n = 15) and without (n = 23) GAD underwent segmentation and between-group volumetric comparisons of the basolateral amygdala (BLA), ventral hippocampal subiculum (vSC), and mediodorsal medial magnocellular (MDm) area of the thalamus. RESULTS: Children with GAD displayed significantly larger vSC compared to healthy peers, F(1, 31) = 6.50, pFDR = .048. On average, children with GAD presented with larger BLA and MDm, Fs(1, 31) ≥ 4.86, psFDR ≤ .054. Exploratory analyses revealed right-hemispheric lateralization of all measures, most notably the MDm, F(1, 31) = 8.13, pFDR = .024, the size of which scaled with symptom severity, r = .83, pFDR = .033. CONCLUSION: The BLA, vSC, and MDm are believed to be involved in the regulation of anxiety and stress, both individually and collectively through the excitation and inhibition of the L-HPA axis. All were found to be enlarged in children with GAD, perhaps reflecting hypertrophy related to hyperexcitability, or early neuronal overgrowth. Longitudinal studies should investigate the relationship between these early morphological differences and the long-term subcortical atrophy previously observed.

Connectome-based predictive modelling estimates individual cognitive status in Parkinson's disease.

INTRODUCTION: The progressive nature of Parkinson's disease (PD) affords emphasis on accurate early-stage individual-level assessment of risk and intervention appropriateness. In PD, cognitive impairment (CI) may follow or precede motor symptoms but are generally underdetected. In addition to impeding daily functioning and quality of life, CIs increase the risk for later conversion to dementia, providing a pressing need to develop novel tools to detect and interpret them. Connectome-based predictive modelling (CPM) is an emerging machine-learning approach to individual prediction that holds translational promise due to its noninvasiveness and simple implementation. The aim of this study was to investigate CPM's potential to predict and understand CIs in PD. METHODS: Resting-state functional connectivity from 58 patients with PD of varying cognitive status was used to train a CPM-model to predict a global cognitive composite (GCC) score. The model was validated using cross-validation, permutation testing, and internal stability analyses. The combined predictive strength of two brain connectivity networks, positive and negative, directly and inversely correlated with GCC, respectively, was assessed. RESULTS: The model significantly predicted individual GCC scores, r = 0.63, pperm < .05. Separately, the positive and negative networks were similar in performance, rs ≥ .58, ps < .05, but varied in anatomical distribution. CONCLUSIONS: This study identified a connectome predictive of cognitive scores in PD, with features overlapping with established and emerging evidence on aberrant connectivity in PD-related CIs. Overall, CPM appears promising for clinical translation in this population, but longitudinal studies with out-of-sample validation are needed.

Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee.

Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications. Expert-based consensus and recommendations for best practice and quality of patient care were developed to support clinicians, scientists, and their multidisciplinary teams, as well as patients and care providers and will be regularly updated.

Non­synchronous bilateral metastatic ovarian cancer originating from small bowel adenocarcinoma with multidisciplinary treatment: A case report.

Primary small bowel adenocarcinoma (SBA) is a rare gastrointestinal cancer with a low incidence of ovarian metastasis. Differential diagnosis of metastatic and primary ovarian cancer is often challenging. The present study reported the case of a 45-year-old woman with jejunal adenocarcinoma who presented with right ovarian, left ovarian, abdominopelvic implant and local recurrent bowel wall metastases successively after primary tumor resection. The ovarian masses of the patient originated from SBA, which was confirmed by immunohistochemical results. Following four comprehensive evaluations by an experienced multidisciplinary team (MDT) during the disease period, the patient underwent four operations, 28 cycles of chemotherapy, 24 cycles of targeted therapy and maintenance therapy for 8 months. As of February 2023, the patient has survived for 73 months and has a high quality of life. It is suggested that when a patient with SBA presents with an ovarian mass, the differential diagnosis between metastatic ovarian cancer and primary ovarian cancer mainly relies on immunohistochemistry. After a comprehensive evaluation by an experienced MDT, surgical resection is the primary treatment for advanced SBA, thus demonstrating some benefits for patients.

Neural correlates of episodic memory decline following electroconvulsive therapy: An exploratory functional magnetic resonance imaging study.

BACKGROUND: Electroconvulsive therapy (ECT) is an efficient and rapid-acting treatment indicated for severe depressive disorders. While ECT is commonly accompanied by transient memory decline, the brain mechanisms underlying these side effects remain unclear. AIMS: In this exploratory functional magnetic resonance (fMRI) study, we aimed to compare effects of ECT versus pharmacological treatment on neural response during episodic memory encoding in patients with affective disorders. METHODS: This study included 32 ECT-treated patients (major depressive disorder (MDD), n = 23; bipolar depression, n = 9) and 40 partially remitted patients in pharmacological treatment (MDD, n = 24; bipolar disorder, n = 16). Participants underwent neuropsychological assessment, a strategic picture encoding fMRI scan paradigm, and mood rating. The ECT group was assessed before ECT (pre-ECT) and 3 days after their eighth ECT session (post-ECT). RESULTS: Groups were comparable on age, gender, and educational years (ps ⩾ 0.05). Within-group analyses revealed a selective reduction in verbal learning and episodic memory pre- to post-ECT (p = 0.012) but no decline in global cognitive performance (p = 0.3). Functional magnetic resonance imaging analyses adjusted for mood symptoms revealed greater activity in ECT-treated patients than pharmacologically treated No-ECT patients across left precentral gyrus (PCG), right dorsomedial prefrontal cortex (dmPFC), and left middle frontal gyrus (MFG). In ECT-treated patients, greater decline in verbal learning and memory performance from pre- to post-ECT correlated with higher PCG response (r = -0.46, p = 0.008), but not with dmPFC or MFG activity (ps ⩾ 0.1), post-ECT. CONCLUSIONS: Episodic memory decline was related to greater neural activity in the left PCG, but unrelated to increased dmPFC and MFG activity, immediately after ECT.

Early longitudinal changes in brain structure and cognitive functioning in remitted patients with recently diagnosed bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) who are presenting with cognitive impairment and associated structural brain abnormalities have generally a poorer clinical outcome. This study aims to map the early longitudinal trajectories in brain structure and cognition in patients with recently diagnosed BD. METHODS: Fully or partially remitted patients with a recent diagnosis of BD and matched healthy controls (HC) underwent structural MRI and neuropsychological testing at baseline (BD n = 97; HC n = 66) and again following an average of 16 (range 6-27) months (BD n = 50; HC n = 38). We investigated the differential trajectories in BD vs. HC in cortical gray matter volume and thickness, total cerebral white matter, hippocampal and amygdala volumes, estimated brain age, and cognitive functioning using linear mixed models. Within patients, we further investigated whether brain structural abnormalities detected at baseline were associated with subsequent mood episodes. RESULTS: Compared to HC, patients showed a decline in total white matter volume over time and they had a larger amygdala volume, both at baseline and at follow-up time. Patients further showed lower cognitive performance at both times of investigation with no significant change over time. There were no differences between patients and HC in cortical gray matter volume or thickness, hippocampal volume, or brain-aging patterns. CONCLUSIONS: Cognitive impairment and amygdala enlargement may represent stable markers of BD early in the course of illness, whereas subtle white matter decline may result from illness progression.

FAM family gene prediction model reveals heterogeneity, stemness and immune microenvironment of UCEC.

Background: Endometrial cancer (UCEC) is a highly heterogeneous gynecologic malignancy that exhibits variable prognostic outcomes and responses to immunotherapy. The Familial sequence similarity (FAM) gene family is known to contribute to the pathogenesis of various malignancies, but the extent of their involvement in UCEC has not been systematically studied. This investigation aimed to develop a robust risk profile based on FAM family genes (FFGs) to predict the prognosis and suitability for immunotherapy in UCEC patients. Methods: Using the TCGA-UCEC cohort from The Cancer Genome Atlas (TCGA) database, we obtained expression profiles of FFGs from 552 UCEC and 35 normal samples, and analyzed the expression patterns and prognostic relevance of 363 FAM family genes. The UCEC samples were randomly divided into training and test sets (1:1), and univariate Cox regression analysis and Lasso Cox regression analysis were conducted to identify the differentially expressed genes (FAM13C, FAM110B, and FAM72A) that were significantly associated with prognosis. A prognostic risk scoring system was constructed based on these three gene characteristics using multivariate Cox proportional risk regression. The clinical potential and immune status of FFGs were analyzed using CiberSort, SSGSEA, and tumor immune dysfunction and rejection (TIDE) algorithms. qRT-PCR and IHC for detecting the expression levels of 3-FFGs. Results: Three FFGs, namely, FAM13C, FAM110B, and FAM72A, were identified as strongly associated with the prognosis of UCEC and effective predictors of UCEC prognosis. Multivariate analysis demonstrated that the developed model was an independent predictor of UCEC, and that patients in the low-risk group had better overall survival than those in the high-risk group. The nomogram constructed from clinical characteristics and risk scores exhibited good prognostic power. Patients in the low-risk group exhibited a higher tumor mutational load (TMB) and were more likely to benefit from immunotherapy. Conclusion: This study successfully developed and validated novel biomarkers based on FFGs for predicting the prognosis and immune status of UCEC patients. The identified FFGs can accurately assess the prognosis of UCEC patients and facilitate the identification of specific subgroups of patients who may benefit from personalized treatment with immunotherapy and chemotherapy.

Review of the Potential Therapeutic Effects and Molecular Mechanisms of Resveratrol on Endometriosis.

Endometriosis is a hormone-dependent inflammatory disease characterized by the existence of endometrial tissues outside the uterine cavity. Pharmacotherapy and surgery are the current dominant management options for endometriosis. The greater incidence of recurrence and reoperation after surgical treatment as well as the adverse effects of medical approaches predispose patients to potential limitations for their long-term usage. Consequently, it is essential to explore novel supplementary and alternative drugs to ameliorate the therapeutic outcomes of endometriotic patients. Resveratrol is a phenolic compound that has attracted increasing interest from many researchers due to its pleiotropic biological activities. Here, we review the possible therapeutic efficacies and molecular mechanisms of resveratrol against endometriosis based on in vitro, animal, and clinical studies. The potential mechanisms of resveratrol include anti-proliferative, pro-apoptotic, anti-angiogenic, anti-oxidative stress, anti-invasive and anti-adhesive effects, thereby suggesting that resveratrol is a promising candidate for endometriosis. Because most studies have investigated the effectiveness of resveratrol on endometriosis via in vitro trials and/or experimental animal models, further high-quality clinical trials should be undertaken to comprehensively estimate the clinical application feasibility of resveratrol on endometriosis.

Discriminating promiscuous from target-specific autoantibodies in COVID-19.

Diverse autoantibodies were suggested to contribute to severe outcomes of COVID-19, but their functional implications are largely unclear. ACE2, the SARS-CoV-2 receptor and a key regulator of blood pressure, was described to be one of many targets of autoantibodies in COVID-19. ACE2 in its soluble form (sACE2) is highly elevated in the blood of critically ill patients, raising the question of whether sACE2:spike complexes induce ACE2 reactivity. Screening 247 COVID-19 patients, we observed elevated sACE2 and anti-ACE2 IgG that were poorly correlated. Interestingly, levels of IgGs recognizing ACE2, IFNα2, and CD26 strongly correlated in severe COVID-19, with 15% of sera showing polyreactivity versus 4.1% exhibiting target-directed autoimmunity. Promiscuous autoantibodies failed to impair the activity of ACE2 and IFNα2, while only specific anti-IFNα2 IgG compromised cytokine function. Our study suggests that the detection of autoantibodies in COVID-19 is often attributed to a promiscuous reactivity, potentially misinterpreted as target-specific autoimmunity with functional impact.

Outcome of SARS-CoV2 infection in hematopoietic stem cell transplant recipients for autoimmune diseases.

Hematopoietic stem cell transplant (HSCT) recipients may be at high risk of mortality from coronavirus disease 2019 (COVID-19). However, specific data on COVID-19 after treatment with HSCT in patients affected by autoimmune diseases (ADs) are still lacking. In this multicenter observational study of the European Society for Blood and Marrow Transplantation (EBMT), clinical data on COVID-19 in 11 patients affected by severe ADs treated with HSCT (n = 3 allogeneic transplant; n = 8 autologous transplant) are reported. All patients were symptomatic during the initial phase of the SARS-CoV-2 infection. At screening, 5 patients reported upper respiratory symptoms, 3 patients had cough without oxygen requirement, and 6 patients exhibited extra-pulmonary symptoms. Four cases developed a lower respiratory tract disease (LRTD). Hospitalization was required in 6 cases, without necessity of intensive care unit (ICU) admission and/or ventilation/supplemental oxygen. Different interventions were adopted: remdesivir (n = 1), nirmatrelvir/ritonavir (n = 1), sotrovimab (n = 1), immunoglobulins (n = 1). At last follow-up, all patients are alive and had resolution of the infection. The current analysis describing the mild-moderate course of COVID-19 in transplant recipients affected by ADs, similar to the course observed in ADs under standard treatments, provides useful information to support the delivery of HSCT programs in this field. Vaccination and new treatments available for SARS-CoV-2 may be useful to further minimize the risk of infection.

Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis.

Granulomatosis with Polyangiitis (GPA) is a small vessel vasculitis typically associated with release of neutrophil extracellular traps (NETs) by activated neutrophils. In this study, we further aimed to investigate the contributions of neutrophils and NETs to the complex disease pathogenesis. We characterized the phenotype of neutrophils and their capacity to induce NETs. In addition, the level of circulating NETs, determined by neutrophil elastase/DNA complexes, and the capacity of patient sera to degrade NETs were investigated from blood samples of 12 GPA patients, 21 patients with systemic lupus erythematosus (SLE) and 21 healthy donors (HD). We found that GPA patients had significantly increased levels of low-density granulocytes (LDGs) compared to HD, which displayed an activated and more immature phenotype. While the propensity of normal-density granulocytes to release NETs and the levels of circulating NETs were not significantly different from HD, patient sera from GPA patients degraded NETs less effectively, which weakly correlated with markers of disease activity. In conclusion, increased levels of immature and activated LDGs and altered degradation of circulating NETs may contribute to pathogenesis of GPA, potentially by providing a source of autoantigens that trigger or further enhance autoimmune responses.