Search Results (3,664)

Immunotherapy is a promising treatment option for many cancers but is associated with the development of peripheral neuropathy in some patients. This retrospective cross-sectional EMR-based prevalence study was performed at MD Anderson Cancer Center with an aim to define the prevalence and epidemiology of Programmed Cell Death Protein 1 (PD-1) inhibitor-associated polyneuropathy. A total of 12,092 patients treated with a PD-1 inhibitor between 4 March 2016 and 18 June 2023 were identified and those on immunotherapy monotherapy were isolated. A total of 817 patients had documented neuropathy-associated with PD-1 inhibitor exposure, corresponding to a prevalence of 6.76% (6.76%, 95% CI 6.31–7.22). Data was stratified to assess for association between peripheral neuropathy and agent, sex, race, ethnicity, smoking and diabetes status. Patients identifying as “Other” race had higher prevalence of neuropathy compared to White or Caucasian patients (OR 1.514, p = 0.0189) and non-Hispanic or Latino patients had higher prevalence of neuropathy compared to Hispanic or Latino patients (OR 1.502, p = 0.0078). Current-smokers had significantly lower prevalence of neuropathy compared to never-smokers (OR 0.716, p = 0.0368). These disparities underscore the importance of further investigation in genetics and mechanisms to identify therapeutic interventions for PD-1 inhibitor-associated peripheral neuropathy. Full article

Background/Objectives: Patients with advanced non-malignant chronic conditions experience illness burdens and palliative care needs comparable to those of oncology patients, yet palliative care is often introduced late. Identifying individuals with potential palliative care needs is complex, and although multiple tools exist, the most appropriate approach for assessing needs in this population remains unclear. This umbrella review aimed to identify and evaluate tools used to systematically assess palliative care in adults with advanced non-malignant chronic conditions, with a specific focus on their content, structure, and psychometric properties. Methods: An umbrella review of systematic reviews was conducted in accordance with the Joanna Briggs Institute (JBI) guidance. Four electronic databases (Cochrane Library, CINAHL, PubMed, and PsycINFO) were searched from inception to 30 June 2025. Eligible systematic reviews were screened, critically appraised, and synthesized narratively. Results: Seven systematic reviews met the inclusion criteria, collectively identifying 35 unique needs-assessment tools. Five tools (SPICT, GSF-PIG, QUICK GUIDE, NECPAL, and P-CaRes) incorporated both general and disease-specific palliative care indicators. At the same time, four (PC-NAT, SPEED, NAT, and IPOS) addressed needs across physical, psychological, social, and spiritual domains. Psychometric data were available for six tools across three reviews. The original NAT and SPICT demonstrated good reliability; however, the Dutch version of the NAT showed poor validity. SPEED and one unnamed palliative care tool showed good reliability, whereas the Surprise Question demonstrated unclear validity. Italian-SPICT and Israeli-NECPAL exhibited strong content validity. Conclusions: Despite limited evidence, the NAT: PD-HF shows particular promise for identifying palliative care needs in patients with heart failure. Tools such as SPICT and NECPAL are widely used and adapted for advanced non-malignant chronic conditions, but further psychometric evaluation is required. Additional studies are needed to clarify the clinical utility of these tools for broader implementation in assessing palliative care needs. Full article

Dihydrolipoamide dehydrogenase (DLD) deficiency (MIM #246900) is a rare autosomal recessive mitochondrial disorder caused by pathogenic variants in the DLD gene, which encodes the E3 subunit common to multiple mitochondrial enzyme complexes, including pyruvate dehydrogenase (PDHc) and α-ketoglutarate dehydrogenase (αKGDHc). Although genotype–phenotype correlations have been described, the precise bioenergetic consequences of DLD dysfunction remain poorly defined. Here, we applied high-resolution respirometry using a novel single-run protocol that allows simultaneous assessment of mitochondrial respiratory capacity and, critically, distinguishing between PDHc- and αKGDHc-linked respiration within the same assay. Fibroblasts from six genetically confirmed DLD-deficient patients with distinct pathogenic variants and clinical severities exhibited a consistent reduction in maximal and complex I-linked respiration. The most severe cases (c.1436A>T; p.D479V) showed combined PDHc and αKGDHc impairment, whereas milder genotypes displayed isolated PDHc dysfunction. This mechanistic distinction likely underlies the variable clinical response to ketogenic therapy, which depends on intact αKGDHc function. Analysis of the mitochondrial mass and mtDNA copy number revealed no global reduction, indicating intrinsic enzymatic dysfunction as the primary defect. Collectively, this study defines a reproducible bioenergetic signature of DLD deficiency and introduces an integrated one-run diagnostic strategy for delineating enzyme-specific mitochondrial defects, providing a framework for mechanistic and therapeutic investigations. Full article

Background/Objective: Central pathophysiological heterogeneity among Parkinson’s disease (PD) motor subtypes has been increasingly recognized, yet subtype-specific peripheral disturbances are limited. We aimed to characterize demographic, biochemical, and neurophysiological differences among PD motor subtypes, evaluate hematoinflammatory effects on peripheral and proximal motor conduction, and identify prognostic phenotypic biomarkers. Methods: A total of 110 participants (60 idiopathic PD patients (30 akinetic-rigid (AR), 30 tremor-predominant (TD), and 50 age- and sex-matched healthy controls (HCs)) were enrolled. Demographic data, nerve conduction studies (NCS) including detailed F-wave analysis, and hematoinflammatory markers were collected. Kruskal–Wallis, linear mixed models, multivariable regression, and ROC analyses were applied. Results: Hematoinflammatory indices were elevated in both subtypes compared with HCs, with more pronounced changes in AR (mean platelet volume (MPV) H = 4.367, p = 0.003; systemic inflammatory response index (SIRI) H = 3.929, p = 0.004). AR showed severe upper-limb–predominant motor involvement (median motor onset latency H = 55.30, p < 0.001; amplitude H = 50.52, p = 0.04; conduction velocity H = 49.15, p < 0.001), whereas TD showed milder, lower-limb–predominant changes (tibial motor onset latency H = 19.89, p < 0.001; amplitude H = 51.50, p = 0.02; velocity H = 15.39, p < 0.001). AR also demonstrated prolonged minimal (Fmin)/mean (Fmean) ulnar F-wave latencies versus TD (respectively, H = 10.51, p = 0.001; H = 8.79, p = 0.003), with both showing increased tibial Fmean/Fmax latencies. Platelet–eosinophil indices independently predicted ulnar F-latencies (B = 0.104–0.105; p = 0.001; model R² = 0.21–0.39). Select F-wave metrics yielded ROC AUCs ≈ 0.65–0.92 (ulnar Fmin AUC ≈ 0.92 vs. HCs); AR achieved sensitivity/specificity ≈ 70–74%. Conclusions: The AR subtype showed increased hematoinflammatory changes, specifically in MPV and SIRI, as well as a tendency toward more pronounced proximal motor and peripheral nerve conduction impairment compared with TD. Platelet–eosinophil indices and F-wave metrics may represent potential candidate markers for diagnostic or stratification purposes in PD subtyping and could possibly aid in prognostic estimation. Full article

Chronic lymphocytic leukemia (CLL) is a heterogenous disease, with varied clinical outcomes. Multiplex assays used to measure soluble immune checkpoints offer a less laborious method of monitoring patients with CLL, but none of these panels have been validated. The aim of the study was to assess soluble immune checkpoint profiles in patients with CLL and to correlate these with independent prognostic markers such as β2-microglobulin (B2M), Rai stage, fluorescence in situ hybridization (FISH) status, and the International Prognostic Index for Chronic Lymphocytic Leukemia (CLL-IPI). We measured plasma levels of soluble interleukin-2 receptor alpha (sCD25), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), galectin-9, programmed cell death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) using cytometric bead array-based assays. We further measured plasma levels of B2M using an enzyme-linked immunosorbent assay (ELISA) kit. Soluble immune checkpoints were correlated with prognostic markers. The plasma levels of sCD25, TIM-3, galectin-9, PD-1, and PD-L1 were significantly increased in patients with CLL compared to the control group, p < 0.0001. Galectin-9 plasma levels were directly associated with B2M levels (β = 0.65, p = 0.012). Our findings suggest that galectin-9 may provide valuable prognostic significance for patients with CLL. Full article

Contaminated water detoxification remains difficult due to the presence of persistent halo-organic contaminants, such as perfluorooctanoic acid (PFOA) and chlorophenols, which are chemically stable and resist conventional purification methods. Functionalized membrane-based separation and decontamination have garnered immense attention in recent years. Commercially available microfiltration membrane (PVDF) and polymeric non-woven fiber filters (glass and composite) are functionalized with poly(methacrylic acid) (PMAA) that shows outstanding pH-responsive performance and tunable water permeability under ambient conditions perfect for environmental applications. Polymer loading based on weight gain measurements on PMAA–microglass composite fibers (137%) and microglass fibers (116%) confirmed their extent of functionalization, which was significantly greater than that of PVDF (25%) due to its widely effective pore diameter. Presence of chemically active hydrogel within PVDF matrix was validated by FTIR (hydroxyl/carbonyl) stretch peak, substantial decrease in contact angle (68.8° ± 0.5° to 30.8° ± 1.9°), and decrease in pure water flux from 509 to 148 LMH/bar. Nanoparticles are generated both in solution and within PVDF using simple redox reactions. This strategy is extended to PVDF-PMAA membranes, which are loaded with Fe/Pd nanoparticles for catalytic conversion of 4-chlorophenol and PFOA, forming Fe/Pd-PVDF-PMAA systems. A total of 0.25 mg/L Fe/Pd nanoparticles synthesized in solution displayed alloy-type structures and demonstrated a strong catalytic performance, achieving complete hydrogenation of 4-chlorophenol to phenol and 67% hydrogenation of PFOA to its reduced form at 22–23 °C with ultrapure hydrogen gas supply at pH 5.7. These results underscore the potential of hybrid polymer–nanoparticle systems as a novel remediation strategy, integrating tunable separation with catalytic degradation to overcome the limitations of conventional water treatment methods. Full article

Background: Gastrointestinal (GI) symptoms are highly prevalent in people receiving dialysis and contribute to malnutrition and poor quality of life. We examined the prevalence and severity of GI symptoms in Jordanian adults with end-stage kidney disease (ESKD) treated with hemodialysis (HD) or peritoneal dialysis (PD). Methods: In this cross-sectional study, consecutive adults with ESKD receiving maintenance HD at Al-Karak Teaching Hospital or PD at Al-Basheer Hospital were interviewed using the validated Arabic Gastrointestinal Symptom Rating Scale (GSRS). Domain and total scores (range 1–7) were compared between modalities; a GSRS total score ≥3 defined at least mild overall GI symptom burden. Results: Among 168 ESKD participants (mean age 43.4 ± 15.3 years; 116 HD, 52 PD), 92.2% reported at least one GI symptom. The prevalence of GSRS-defined symptoms was greater in PD (94.2%) than HD (91.4%). PD was associated with significantly higher mean scores in all GSRS domains (reflux, abdominal pain, indigestion, diarrhea, constipation) and a higher total GSRS score (3.33 ± 1.36 vs. 2.36 ± 0.71; p < 0.01 for all comparisons). Upper GI bleeding (UGIB) requiring hospitalization after dialysis initiation occurred more often in HD than PD (15.5% vs. 3.8%; OR 4.59; 95% CI 1.03–20.58). Conclusions: This study demonstrated that dialysis patients had a high prevalence of GI symptoms, with an elevated severity in patients on PD. These findings highlight the need for routine structured assessment of GI symptoms and modality-specific management strategies in dialysis units, particularly for patients on PD. Full article

Nodal marginal zone lymphoma (NMZL) is an indolent B-cell lymphoma that may pose diagnostic challenges due to the absence of distinct markers. In rare atypical cases, an overabundance of PD1+ T follicular helper (TFH) cells in tumor tissue may mimic peripheral T-cell lymphoma (PTCL) of TFH origin, further complicating the diagnosis. A 72-year-old woman with progressive lymphadenopathy had a cervical lymph node biopsy showing a disrupted architecture with monomorphic nodules of CD20+/MNDA+ B-cells and a prominent central population of proliferating CD4+/PD1+ T-cells, initially suggestive of a PTCL-TFH. The bone marrow contained aggregates of CD20+ B-cells intermixed with CD3+/CD4+/PD1+ T-cells. Next-generation sequencing (NGS) revealed clonal immunoglobulin heavy-chain rearrangements in the lymph node and bone marrow, with T-cell receptor genes displaying a polyclonal pattern. Targeted NGS showed no PTCL-related alterations but identified NMZL-associated mutations with different distributions across lymph node and bone marrow compartments. NOTCH2 mutations (c.6418C>T; p.Gln2140*) were found in both tissues, while the (c.69+2T>A; p.?) TNFRSF14 gene mutation was only detected in the lymph node. The KMT2D gene displayed a frameshift variant in the lymph node (c.4801_4802delinsT; p.Arg1601Leufs*3) and an in-frame deletion (c.11756_11758del; p.Gln3919del) in the bone marrow. Notably, NGS and digital droplet PCR confirmed a TP53 frameshift mutation (c.902del; p.Pro301Glnfs*44) with a fractional abundance of 0.31% in the lymph node and a (c.742C>T; p.Arg248Trp) mutation (0.309%) in the bone marrow. Results underscore the importance of NGS-based clonality to diagnose NMZL with prominent PD1+ T-cell hyperplasia, and prompt further investigation into tissue-specific mutational signatures in these unusual cases. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) show durable efficacy in tumors with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), yet clinical responses remain heterogeneous. This study aimed to define immune subgroups within dMMR/MSI-H tumors and develop a reproducible transcriptomic signature predictive of ICI response. Methods: Four MSI-H-enriched cancer types (UCEC, COAD, READ, STAD) from The Cancer Genome Atlas were analyzed. Tumors were stratified by immune cell infiltration (MCP-counter immune composite score) and T-cell-inflamed gene expression profiles (GEP score). Integrating these two axes defined four immune subgroups. Differential expression, random forest feature selection, and pathway enrichment were performed to identify immune programs. A 20-gene immune signature representing the most immune-active subgroup was developed and validated across TCGA, GEO (GSE39582), and IMvigor210 cohorts. Results: Among the four subgroups, the most immune-active group showed strong activation of interferon signaling, antigen presentation, and T-cell-mediated pathways. The 20-gene signature—including CD74, STAT1, TAP1, and HLA-class genes—achieved high reproducibility (mean AUC = 0.95 ± 0.02; accuracy ≈ 89%). In the IMvigor210 cohort, this signature identified tumors with higher PD-L1 blockade response (55.6% vs. 32.8%, p = 0.034) and improved survival trends in the TMB-high subset. Conclusions: The proposed 20-gene signature quantitatively captures immune heterogeneity in dMMR/MSI-H tumors and serves as a practical, interpretable biomarker to identify true ICI responders and guide precision immunotherapy. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder shaped by genetic factors such as LRRK2 and GBA1 mutations, as well as dietary and metabolic influences. Food-derived plasma metabolites—including caffeine, paraxanthine, trigonelline, piperine, and sitosteryl hexoside—have emerged as promising, accessible biomarkers for early detection, progression monitoring, and therapeutic targeting, yet their longitudinal behavior and genetic interactions remain insufficiently characterized. Using the Parkinson’s Progression Markers Initiative (PPMI) cohort (n = 455; 303 PD patients, 152 controls), we quantified plasma levels of these metabolites by quantitative LC-MS/MS with batch correction, examining sporadic PD and genetically defined subgroups (LRRK2-PD [PDL], GBA1-PD [PDG], dual-mutation PD [PDGL], and prodromal equivalents). Baseline one-way ANOVA showed significantly lower caffeine and paraxanthine in PDL (p = 0.0467, p = 0.0178) and PDG (p = 0.0408), reduced piperine in PDL (p = 0.0009), PDG (p = 0.0257), and prodromal LRRK2 (p = 0.0168), and elevated sitosteryl hexoside in PDG (p = 0.0184). Longitudinal regression analyses revealed that in sporadic PD, caffeine negatively correlated with MDS-UPDRS parts I (β = −2, p = 0.0475) and III (β = −7.2, p = 0.007), trigonelline declined over time and was inversely associated with part III (β = −1.7, p = 0.0069), and sitosteryl hexoside negatively correlated with parts II (β = −68.3, p = 0.042) and III (β = −74.1, p = 0.0425). In PDL, sitosteryl hexoside inversely correlated with part I (β = −54.2, p = 0.0049), while in PDGL, paraxanthine showed negative associations with part II (β = −18.5, p = 0.00327). These findings demonstrate subgroup-specific alterations in food-derived metabolites and consistent inverse associations with PD severity, supporting their potential as non-invasive biomarkers, particularly in LRRK2/GBA1 mutation carriers, and highlighting the need for longitudinal validation and dietary intervention trials to advance personalized PD management. Full article

Objectives: The aim of this work was to investigate whether Bacteroides vulgatus (BV), Clostridium perfringens (CP), Parabacteroides distasonis (PD), and Ruminococcus albus (RA) lysates modulate the secretion of IL-17, INF-γ, IL-2, and TGF-β 1 by human HT-29 cells, PBMCs, and monocytes (MON). Results: CP lysate significantly lowered IL-17 secretion by HT-29 cells vs. control (p < 0.05), but only at a dose of 100 µg. RA lysate reduced IL-17 secretion by HT-29 cells vs. control (p < 0.05), but only at a dose of 400 µg, whereas PD lysate significantly decreased IL-17 secretion by HT-29 cells vs. control (p < 0.05) at both doses. The secretion of IL-17 by PBMCs was significantly reduced after administration of BV and PD lysates (100 µg). BV and PD lysates (400 µg) also significantly decreased IL-17 secretion by MON vs. control (p < 0.05). The secretion of INF-γ by HT-29 cells was significantly lowered vs. control (p < 0.05) after administration of PD and CP lysates (400 µg). CP lysates (100 µg and 400 µg) also significantly reduced INF-γ secretion by MON compared with control (p < 0.05). The secretion of INF-γ by PBMCs was significantly reduced vs. control (p < 0.05) after administration of BV and CP lysates (400 µg). Conclusions: In PBMCs, HT-29 cells, and MON, INF-γ and IL-17 concentrations were significantly lowered by selected bacterial lysates in a dose-dependent manner. However, the low values detected in this experiment may not have an impact on systemic immune status. Full article

Advanced two-dimensional (2D) beam steering is essential for unlocking the full potential of terahertz (THz) systems in future 6G communications and high-resolution imaging. However, achieving wide-angle, high-speed, and high-precision 2D beam control within a compact THz platform remains a significant challenge. In this work, we experimentally demonstrate an optoelectronic $2\times 2$ THz antenna array that enables flexible 2D beam steering, beam hopping, and beam scanning around the 300 GHz band. This work employs a $2\times 2$ microstrip patch antenna (MPA) array directly driven by InGaAs/InP UTC-PDs on a silicon carbide (SiC) substrate. The relative phases of the four radiating elements are precisely programmed using an optical phased array (OPA), which provides fully decoupled and low-latency phase control in the optical domain. Experimentally, we demonstrate 2D beam steering and 2D beam hopping among three representative directions at a polar angle of ${25}^{\circ }$ and azimuth angles of ${60}^{\circ }$, ${180}^{\circ }$, and ${300}^{\circ }$. Furthermore, continuous 2D beam scanning at a fixed polar angle of ${25}^{\circ }$ is achieved, enabling a full ${360}^{\circ }$ azimuth sweep within 0.43 s while maintaining high beam quality. These results confirm that the proposed UTC-PD based $2\times 2$ MPA array provides a practical and robust approach for 2D THz beam manipulation, and offers strong potential for future 6G wireless links and THz imaging applications. Full article

Background: Chlorhexidine (CHX) is an effective antiseptic rinse for managing gingival inflammation; however, side effects such as staining and altered taste limit its long-term use. StellaLife^® (SL), an herbal-based mouth rinse and a gel, has shown promising in vitro effects, including enhanced biocompatibility and wound healing. This study aimed to compare the clinical efficacy of SL and 0.12% CHX in an experimental gingivitis model. Methods: In this randomized, controlled, cross-over clinical trial, 34 dental students received both treatment regimens in alternating two-week phases following prophylaxis. Group 1 used SL (mouth rinse and the gel) and then crossed over to CHX with placebo gel. Group 2 followed the reverse sequence. Participants refrained from oral hygiene during treatment phases. Clinical parameters and gingival crevicular fluid (GCF) were assessed at baseline and post-treatment. Paired t-tests and Bonferroni corrections were applied (p < 0.05). Bacterial count was determined by an external laboratory using a PCR test. Mean values for bacteria after SL and CHX use measured in genome copies/mL for Aggregatibacter actinomycetemcomitans, P. gingivalis, T. denticola, T. forsythia and F. nucleatum. Results: No statistically significant differences were observed between the SL and CHX groups for PI (p = 0.057), GI (p = 0.960), PD (p = 0.112), BOP (p = 0.895), GR (p = 0.768), CAL (p = 0.112), or GCF (p = 0.951). Both regimens improved periodontal parameters similarly. No significant differences were found between CHX and SL use in respect to periodontal pathogenic bacteria in the oral cavity. Conclusions: SL demonstrated clinical efficacy comparable to CHX in managing experimental gingivitis. Given its favorable safety profile, SL may serve as a promising alternative to CHX, though larger and longer-term studies are warranted. Full article

Over the years, there has been extensive research conducted on Parkinson’s Disease (PD), a neurodegenerative disorder known for causing motor impairment and behavioral changes. In more recent years, the roles of dysregulated microRNAs (miRNAs) in PD pathology have been studied in the hopes of developing new diagnostic methods or even treatments. This systematic review pinpoints and examines studies between 2010 and 2024 that have identified significant dysregulation of miRNAs in patients with PD. Upon filtering out the search results by a series of exclusion criteria, this review was conducted using 56 relevant studies. These studies revealed a vast array of significantly dysregulated miRNAs identified in the samples of patients with PD, when compared to healthy controls. A number of these miRNAs, such as miR-29c-3p, are likely biomarkers for more accurate PD diagnosis, and many, such as miR-485-3p, were found to be involved in PD pathogenesis. With further research, miRNAs could become a helpful diagnostic and prognostic tool for PD, with some of them even being candidate therapeutic targets for future treatments. Full article

Background/Objectives: The global epidemic of type 2 diabetes (T2D) is a critical public health issue, particularly in New Zealand, where prevalence rates are high, especially among Māori and Pacific people. Recent research indicates that dietary interventions, particularly carbohydrate reduction, can lead to the remission or reversal of T2D. However, little is known about how such approaches perform when implemented in routine New Zealand primary care, particularly within high-risk and underserved populations. This study aimed to evaluate changes in HbA1c, diabetes status, and cardiometabolic outcomes among adults with prediabetes and T2D engaged in such a model of care. Methods: This study reports findings from a retrospective, observational, real-world, multi-site clinical audit (service evaluation) of a holistic model of care implemented in three primary care practices in New Zealand. The model of care is characterised by a three-pronged approach: whole food, carbohydrate reduction; a health-coach, behaviour-change-based delivery approach; and community- or peer-based initiatives. Audit data from 106 patients with prediabetes (PD) and T2D were analysed (median follow-up 19 months; IQR 6–32) to assess changes in glycosylated haemoglobin (HbA1c) levels, diabetes status, and cardiometabolic outcomes. Results: We observed an overall reduction in HbA1c (median change −3 mmol/mol (IQR: −7 to 3), p = 0.004), with 32% of patients with T2D at baseline achieving reversal and 44% of those with PD attaining normoglycaemia at final follow-up. Weight loss was associated with greater HbA1c reduction (0.56 mmol/mol decrease per kg lost) and additional improvements seen in lowered alanine aminotransferase (ALT). HDL cholesterol showed a small decline (r = 0.31), and triglycerides and blood pressure showed no significant change, indicating that these measures remained broadly stable over the evaluation period. Conclusions: Given the retrospective and uncontrolled audit design, findings should be interpreted with appropriate caution. However, the consistent improvements observed across multiple practices suggest that carbohydrate-reduction strategies within holistic models of care can meaningfully improve diabetes outcomes in real-world primary care settings. Future research should evaluate longer-term sustainability, implementation fidelity, and the applicability of this model at scale, particularly for Māori and Pacific communities. Full article