This study aimed to investigate whether residual kidney function (RKF) influences perioperative hemodynamic stability in hemodialysis patients. Although anesthesiologists have had the clinical impression that RKF contributes to more stable blood pressure during induction of general anesthesia, this association has not been demonstrated. We hypothesized that RKF was associated with less hypotension at induction. We conducted a single-center retrospective study of hemodialysis patients undergoing elective surgery under general anesthesia. RKF was defined as urine output ≥ 100mL/day. The primary outcome was the lowest systolic blood pressure (SBP) during induction. Propensity score matching was performed. Independent predictors of hypotension were identified using multivariable logistic regression. Of 1,086 patients screened, 882 were analyzed (RKF + 335; RKF- 527). After matching, 160 patients were included in each group. In the matched cohort, the lowest SBP was higher in the RKF + group (111 ± 32 vs. 105 ± 30mmHg; p = 0.044). In the full cohort, both the lowest SBP (112 ± 30 vs. 103 ± 29mmHg; p < 0.001) and the decrease (28 ± 33 vs. 37 ± 31mmHg; p < 0.001) were more favorable in the RKF + group, with lower phenylephrine use (0.09 ± 0.19 vs. 0.16 ± 0.35mg; p = 0.001). Logistic regression confirmed RKF, surgery type, and preoperative SBP as independent predictors. RKF was associated with higher SBP at induction of general anesthesia, independent of anesthetic and vasopressor doses. Preoperative assessment of RKF may help identify dialysis patients at risk of induction-related hypotension.

Abstract Facial paralysis can cause profound functional and psychological impact. Management strategies have evolved significantly, with advances in understanding facial nerve anatomy, nerve physiology, and microsurgical techniques. This review provides a comprehensive overview of surgical strategies for both acute and chronic facial paralysis, highlighting contributions from Chang Gung Memorial Hospital that have shaped contemporary practice. Indications, timing, and selection of interventions—including nerve grafting, nerve transfers, and free functioning muscle transplantations—are examined with emphasis on techniques that restore facial symmetry. Recent developments in the management of acute facial paralysis following oncologic resection and in eyelid reanimation are also discussed. By integrating evidence from published research and institutional experience, this review aims to guide the selection of surgical strategies to enhance facial movement and symmetry.

Adrenocortical carcinoma (ACC) is a devastating disease with few effective treatments. The underlying molecular pathways remain largely unknown. To identify potential pathways and drivers relevant to ACC pathogenesis, we utilized histologically normal adrenals from heterozygous multiple endocrine neoplasia type 1 (Men1) mice to study early adrenocortical tumorigenesis. Employing mass spectrometry based proteomic profiling, we identified 681 proteins of which 52 displayed significant differential regulation in the adrenal tissues of heterozygous Men1 mice in comparison to their wild-type counterparts. Among these were fatty acid synthase (FASN) and ATP-citrate lyase (ACLY), two enzymes previously shown to be upregulated in several other types of tumors. To assess the functional impact of ACLY and FASN in ACC, we used H295R cells as the primary model. Cells were treated with SB-204990 (ACLY inhibitor) or C75 (FASN inhibitor), which both showed a dose-dependent antiproliferative effect. Lipidomic analysis revealed a significant reduction of palmitic acid and palmitoleic acid in treated cells compared to controls, supporting a mechanistic link between ACLY/FASN activity and lipid biosynthesis. Finally, data from the Cancer Genome Atlas showed significantly diminished survival outcomes among ACC patients exhibiting high ACLY or FASN expression. These findings underscore the potential importance of exploring the inhibition of lipid synthesis as a promising avenue for further research in the context of human ACC.

Asthma is a prevalent chronic inflammatory disease in childhood, associated with high morbidity and impact on quality of life. The clinical variability of symptoms can make diagnosis difficult, making a detailed analysis of the clinical profile essential for proper management. The clinical and epidemiological profile of children diagnosed with asthma who were followed in an immunoallergology outpatient clinic of a university hospital was obtained. This was an observational, retrospective, and descriptive study, conducted through the analysis of 30 medical records of pediatric patients diagnosed with asthma. Demographic variables, initial symptoms, allergic comorbidities, family history, hospitalizations, laboratory tests (total and specific IgE, immediate reading skin test), spirometry, and instituted treatment were evaluated. The data was organized in spreadsheets and analyzed using descriptive statistics. The average age of the patients was 7.6 years, with a predominance of illnesses. The most frequent symptoms were recurrent dry cough, wheezing, and exertional dyspnea, with functional impact such as school absenteeism. A family history of allergic diseases was present in 76.6% of cases. A high prevalence of allergic comorbidities was observed, suggesting atopic march. Patients with positive allergy tests showed greater clinical severity and a higher number of hospitalizations. Spirometry revealed mild to moderate obstructive ventilatory disorder in part of the sample. Treatment with inhaled corticosteroids showed good clinical response and satisfactory adherence. The findings demonstrate the predominance of asthma with an allergic component, highlighting the importance of specialized follow-up, environmental control, and appropriate treatment for disease management and quality of life improvement.

Background: Pain is a common and clinically important symptom in hemodialysis, yet its functional impact and determinants remain insufficiently characterized. This study examined factors associated with pain interference using the Pain Effects Scale (PES) in maintenance hemodialysis patients. Methods: In a cross-sectional study, 73 adults receiving thrice-weekly hemodialysis completed the PES, assessing the four-week impact of pain on mood, sleep, mobility, work, recreation, and enjoyment of life. Demographic, clinical, and dialysis-related variables—including vascular access type, dialysis vintage, session duration, ultrafiltration volume, predialysis urea, Kt/V, urea reduction ratio, comorbidities, and transplant history—were extracted from medical records. Associations were evaluated using parametric and non-parametric tests. Results: PES scores indicated substantial pain interference. Older age was positively correlated with higher PES scores (r = 0.32, p = 0.006), and patients with ischemic heart disease had significantly higher PES values than those without (23.1 ± 6.7 vs. 17.3 ± 6.2; p = 0.012). Willingness to pursue transplantation showed a non-significant trend toward lower scores. Conclusions: Pain interference in hemodialysis appears largely independent of routine adequacy metrics and most comorbidities, with ischemic cardiovascular disease emerging as an exception. Findings underscore the need for a biopsychosocial approach integrating pain screening with assessment of mood, sleep, neuropathy, musculoskeletal factors, and ischemic symptoms.

Recent advances highlight extracellular vesicles (EVs) as key mediators of intercellular communication, carrying a complex cargo that includes extracellular matrix (ECM) components and associated modulators. Among them, ADAMTS proteases are emerging as pivotal regulators due to their ability to orchestrate precise ECM remodeling events and influence cellular behavior in pathological contexts such as cancer, vascular diseases, and tissue regeneration. Notably, the identification of specific ADAMTS family members within EV populations suggests that EVs may serve as vehicles for paracrine delivery and localized proteolytic activity, enabling spatially and temporally restricted ECM modulation. This review synthesizes current knowledge on the association between EVs and ADAMTS proteases, including their known substrates, and highlights their converging roles in shaping the extracellular landscape. We also discuss key knowledge gaps, especially concerning the diversity of ADAMTS-EV interactions, their functional impact in different physiological and pathological settings, and some reflections regarding their potential translational opportunities.

Current understanding of B cell heterogeneity in diffuse large B cell lymphoma (DLBCL) and its functional impact on disease progression remains incomplete. This study applies single-cell RNA sequencing to identify and characterize a distinct proliferation-related B cell subpopulation in DLBCL, aiming to address this knowledge gap. We utilized dataset GSE182434 from the Gene Expression Omnibus (GEO) database for the analysis, with the aim of identifying genes that are specifically highly expressed in different cell clusters. The copy number variation analysis was performed using B cells of normal samples as the control. Thereafter, the cell-cell communication analysis was implemented to reveal the potential ligand-receptor pairs, and the functional enrichment analysis was performed to uncover the enriched pathways. Further, the potential transcription factors-target genes networks were plotted via SCENIC analysis, and a series of validation assays were implemented using DLBCL cells. The single-cell landscape of DLBCL revealed a reduced proportion of B cells, CD8+ T cells, and naïve T cells. Malignant B cells exhibited chr1q amplification and chr6 deletion, with genes in these regions linked to immune suppression and impaired antigen presentation, respectively. Further subclustering identified a proliferative B cell subcluster (subcluster 2) enriched in nucleotide metabolism and cell cycle pathways. This subcluster was characterized by elevated XBP1 activity, regulating ER stress response, and downregulation of SPIB, RELB, and IRF factors involved in lymphocyte activation and interferon signaling. Functionally, XBP1 silencing suppressed DLBCL cells proliferation and invasion. Cell communication analysis revealed crosstalk between this B cell subpopulation and CD8+ T/NK cells via MIF-(CD74+CXCR4) and LTA-TNFRSF pathways. This analysis has identified and characterized the proliferation-related B cells in DLBCL, which may provide some ideas for the treatment strategies in immune-oncology and cellular therapies.

Real-world effectiveness and safety of upadacitinib in Japanese patients with rheumatoid arthritis: impact of age, renal function, and low-dose therapy.

Alternative splicing is a pervasive gene regulatory mechanism critical for diversifying the human proteome. To systematically investigate its role in cell fate determination, we develop scCHyMErA-Seq, a scalable CRISPR-based exon deletion screening platform integrated with 10x Genomics single-cell transcriptomic readouts. This tool enables efficient exon deletion while simultaneously capturing Cas9/Cas12a guides and polyadenylated transcripts at single-cell resolution. Applying scCHyMErA-Seq to high-throughput profiling of alternative cassette exons, we identify numerous exons with pronounced regulatory effects on gene expression and cell cycle progression. Analysis of the alternative NRF1 exon-7 demonstrates that its inclusion modulates NRF1’s regulatory function by influencing its recruitment to the promoters of target genes. Importantly, gene expression profiles generated using scCHyMErA-Seq accurately recapitulate findings from traditional, labor-intensive orthogonal methods, while offering enhanced scalability and efficiency. Overall, scCHyMErA-Seq represents a versatile platform for systematically unraveling the functional impact of alternative splicing by directly linking specific splicing variants to transcriptional phenotypes.

Tumor Mutational Burden (TMB) is a widely used biomarker for selecting cancer patients for immune checkpoint inhibitor (ICI) therapy. However, TMB alone has limited predictive power, as it fails to account for the functional impact of mutations. We introduce AlphaTMB, a composite biomarker that integrates the quantity of mutations (TMB) with the qualitative assessment of their pathogenicity using AlphaMissense, a deep learning model that predicts the deleteriousness of missense variants. Using a pan-cancer cohort of 1,662 patients from the MSK-IMPACT study who received ICI therapy, we computed three scores per patient: TMB, Alpha (sum of AlphaMissense scores), and AlphaTMB (product of TMB and Alpha). Patients were stratified using both cancer-specific and pan-cancer quantiles. Survival outcomes were evaluated using Kaplan-Meier and multivariate Cox proportional hazards models, controlling for cancer type, age, and ICI regimen. AlphaTMB showed strong correlation with TMB (Spearman ρ = 0.866, p < 0.001), but offered improved prognostic accuracy. Patients in the bottom 80% AlphaTMB group had significantly poorer survival than those in the top 10% (HR < 2.51, p < 0.001), outperforming TMB and Alpha alone. AlphaTMB reclassified borderline cases, identifying subsets with low TMB but high deleterious mutation load, and vice versa. Gene mutation heatmaps and co-occurrence analysis confirmed that to 10% AlphaTMB-high tumors were enriched in mismatch repair and POLE mutations, reflecting a neoantigen-rich, immunotherapy-responsive phenotype. AlphaTMB improves survival prediction beyond TMB alone, better captures immunogenic tumor profiles, and reflects more accurate patient stratification. This AI derived somatic mutations pathogenicity scoring represents a step toward personalized immuno-oncology and merits further validation in prospective studies.

Background and ObjectivesMigraine is a significant disabling neurologic headache disorder globally. Evaluating patient-related outcomes (PROs) is necessary to assess the impact of therapeutic interventions in preventive therapy. An exploratory analysis of data from the EMPOwER study examined the effect of erenumab on PROs in patients with episodic migraine (EM) in regions underrepresented in the pivotal Phase 3 trials of erenumab, specifically Asia, the Middle East, and Latin America.MethodsPatients (N = 900) were randomized (2:3:3) to receive monthly subcutaneous injections of erenumab 140 mg, erenumab 70 mg, or placebo. Adjusted mean changes from baseline in the Headache Impact Test (HIT-6), Migraine Physical Function Impact Diary (MPFID), modified Migraine Disability Assessment (mMIDAS), and EuroQoL 5-dimension 5-level scale (EQ-5D-5L) scores were assessed during the double-blind treatment phase of 3 months.ResultsA statistically significant reduction from baseline in the HIT-6 total score was observed for erenumab 140 mg (−9.34, p < 0.001) and 70 mg (−8.39, p = 0.004) vs placebo (−6.62) at Month 3. Improvement in MPFID scores was also greater in the erenumab groups vs the placebo group (Everyday Activity: 140 mg, −5.61 [p = 0.002]; 70 mg, −4.94 [p = 0.011]; placebo, −3.19; Physical Impairment: 140 mg, −4.27 [p = 0.014]; 70 mg, −3.95 [p = 0.021]; placebo, −2.31) at Month 3. Similar findings were observed for mMIDAS scores (140 mg −8.99 [p < 0.001], 70 mg −8.11 [p = 0.011] vs placebo [−6.59]) and the EQ-5D-5L quality-of-life visual analog scale scores (140 mg 8.13 [p = 0.017], 70 mg 7.08 [p = 0.088] vs placebo [5.22]), although no meaningful between-group difference was noted for index values.DiscussionErenumab showed favorable effects on PROs when compared with placebo in patients with EM. These results enhance the evidence for erenumab as an effective preventive therapy for patients with EM.Trial Registration InformationClinicaltrials.gov/study/NCT03333109.

A biologically plausible model of astrocyte-neuron networks in random and hub-driven connectivity.

Engineering chitosan-functionalized liposomes for targeted drug delivery and biomedical applications.

Impact of Renal Function on Autologous Stem Cell Transplantation (ASCT) Outcomes for AL Amyloidosis

Tunable graphene quantum dot surface chemistry enables fast and selective detection of viral RNA.

The impact of preoperative bladder function on outcomes of simple prostatectomy (SP) is unknown. The goal of this study was to determine if detrusor contractility affects postoperative catheter-free status in patients undergoing SP for benign prostatic hyperplasia (BPH). Patients who underwent SP (either open or minimally invasive) from 2017 to 2024 at our institution and had preoperative urodynamics were identified retrospectively. Bladder contractility index (BCI) was used to categorize patients as normocontractile (BCI ≥ 100) or hypocontractile (BCI < 100). Demographics, preoperative urodynamics, peri-operative characteristics, and postoperative variables were compared between the two groups with postoperative catheter status being the primary outcome. Among 101 SP patients with preoperative urodynamics, 47 had hypocontractile bladders (median BCI 69 vs. 131). Both groups had similar median age, preoperative prostate specific antigen (PSA), and rates of diabetes. The majority of procedures in both the normocontracile and hypocontractile groups were robot-assisted (83% vs. 81%, respectively). Patients in the hypocontractile group were significantly more likely to be catheter dependent pre-operatively (77% vs. 57%, p = 0.04). There was no difference in preoperative prostate size or use of BPH pharmacotherapy. Overall, 97% of hypocontractile and 100% of normocontractile patients were catheter-free following surgery. There were no differences in postoperative outcomes including pathology tissue weight and post-op PSA. This is one of the first studies assessing outcomes of SP in patients with hypocontractile bladders. SP is an effective surgical option for patients with impaired detrusor function including those who are catheter dependent.

Rectal Prolapse.

Computational analysis of missense variants in MT-ND1 and MT-CO2 associated with breast cancer: A functional and structural impact

MRPL55 promotes BC progression as a prognostic biomarker by modulating lipogenesis and cyclin-dependent kinase pathways, from multi-omics to drug repurposing.

Metabolic reprogramming is implicated in the differential response of the CAL-1 plasmacytoid dendritic cell line to autophagy inhibitors.