UNASSIGNED: This prospective study aimed to investigate the influence of weight difference between implanted prosthesis and removed bone in cementless total hip arthroplasty (THA) on hip awareness and patient-reported outcomes.
UNASSIGNED: A total of 48 patients (56 hips) who underwent primary THA were prospectively enrolled. Implanted prosthesis and removed bone were weighed intraoperatively. Forgotten Joint Score (FJS) and Western Ontario and McMaster Universities (WOMAC) scores were obtained before and at 1 and 3 months after surgery. Patients were divided into groups A, B, and C according to the percentile of the weight difference.
UNASSIGNED: The mean weight difference of the implanted prosthesis and removed bone was 117.97 ± 47.35 g. A negative correlation was found among the weight differences of the three groups and 1- and 3-month postoperative FJS (correlation coefficients, -0.331 and -0.734, respectively). A positive correlation was found among the weight difference of the three groups and 3-month postoperative WOMAC (correlation coefficient, 0.403). A significant difference in 3-month postoperative FJS and WOMAC scores was found among the three groups. The mean 3-month postoperative FJS (79.00) of group C was significantly lower than that of group A (93.32) (P < 0.05). The mean WOMAC score (15.83) of group A was significantly lower than that of group C (23.67) (P < 0.05).
UNASSIGNED: The implanted prosthesis is larger than the removed bone in cementless THA. The weight difference is negatively correlated with hip function. The weight difference should be minimized to achieve optimal hip joint awareness.

UNASSIGNED: Segmental spinal deformity results from vertebral compression fracture (VCF) and progressive collapse of the fractured vertebral body (VB). The VB stenting (VBS) systemⓇ comprises a balloon-assisted, expandable, intrasomatic, metal stent that helps maintain the restored VB during balloon removal and cement injection, which minimizes cement leakage. We performed a prospective, multicenter, clinical trial of the VBS system in Japanese patients with acute VCF owing to primary osteoporosis.
UNASSIGNED: Herein, 88 patients, 25 men and 63 women aged 77.4±8.3 years, with low back pain, numerical rating scale (NRS) score of ≥4, and mean VB compression percentage (VBCP) of <60% were enrolled. The primary endpoints were the VBCP restoration rate and reduction in low back pain 1 month and 7 days after VBS surgery, respectively. Secondary endpoints included changes in VBCP, NRS pain score, Beck index, kyphosis angle, and quality of life according to the short form 36 (v2) score. Safety was assessed as adverse events, device malfunctions, and new vertebral fractures.
UNASSIGNED: Overall, 70 patients completed the study. VBS surgery increased the restoration rates of anterior and midline VBCP by 31.7%±26.5% (lower 95% confidence intervals (CI): 26.8) and 31.8%±24.6% (lower 95% CI: 27.2), respectively, and the reduction in NRS pain score was -4.5±2.4 (upper 95% CI: -4.0). As these changes were greater than the predetermined primary endpoint values (20% for VBCP and -2 for NRS score), they were judged clinically significant; these changes were maintained throughout the 12-month follow-up (p<0.001). Likewise, significant improvement was observed in the Beck index, kyphosis angle, and quality of life score, which were maintained throughout the follow-up. There were three serious adverse events. New fractures occurred in 12 patients-all in the adjacent VB.
UNASSIGNED: VBS surgery effectively restored the collapsed VB, relieved low back pain, and was tolerable in patients with acute osteoporotic VB fracture.

Prostate cancer (PCa) is a common male malignancy and early diagnosis is crucial for successful treatment. The current study aims to validate results from a pilot study that demonstrated an inverse association between urine tyrosine and tryptophan levels and the severity of PCa. This study comprised a cohort of 97 patients with benign prostatic hyperplasia, 93 patients diagnosed with localized PCa, 75 patients diagnosed with locally advanced PCa, and 68 patients diagnosed with metastatic PCa. The tyrosine and tryptophan levels in the samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and electrochemical sensors in accordance with the pilot to maintain uniformity for accurately evaluating the data. One-way ANOVA with post Tukey test as well as the Wilcoxon Rank Sum Test were performed. Analyzing 333 patients across PCa stages with consistent methods, we observed no significant differences in tyrosine and tryptophan levels between PCa patients and controls, finally rejecting the use of tyrosine and tryptophan as PCa biomarkers. We did, however, verify the strong correlation between the urinary concentrations of tyrosine and tryptophan found in the pilot study.

OBJECTIVE: To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization (MR) approach.
METHODS: We obtained data pertaining to colorectal cancer from Genome-Wide Association Study (GWAS) datasets and used 91 inflammatory protein markers as the exposure variables. A two-sample MR analysis model was used to assess the causal link between the inflammatory markers and colorectal cancer risk. The robustness of the results was evaluated through heterogeneity, pleiotropy, and sensitivity analyses using 5 MR models: Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Simple Mode, and Weighted Mode. We examined the mRNA expressions of PD-L1, AXIN1, and β-NGF using RT-qPCR in 86 untreated patients with colorectal adenocarcinoma admitted in Nanfang Hospital between December, 2021 and December 2023, and analyzed their correlation with the clinical characteristics of the patients.
RESULTS: Using the IVW model, MR analysis revealed significant causal associations between a reduced risk of colorectal cancer and lowered expressions of AXIN1 (OR=0.866, 95% CI: 0.754-0.994, P=0.040), β-NGF (OR=0.914, 95% CI: 0.843-0.990, P=0.028; OR=0.884, 95% CI: 0.784-0.998, P=0.047 using Weighted Median model), and PD-L1 (OR=0.903, 95% CI: 0.824- 0.989, P=0.028). No significant heterogeneity or pleiotropy was observed, indicating good stability of the results. Sensitivity analysis confirmed the reliability of the findings. The clinical study demonstrated a significant correlation between PD-L1 expression and TNM staging, particularly in stage Ⅳ patients (P=0.007). AXIN1 and β -NGF expression levels were significantly correlated with the degree of tumor differentiation, and their expressions were higher in poorly differentiated samples (P<0.001).
CONCLUSIONS: Lowered expressions of inflammatory protein markers AXIN1, β-NGF, and PD-L1 are causally correlated with a reduced risk of colorectal cancer and their expression levels are associated with TNM staging and tumor differentiation. These markers may thus serve as potential targets for colorectal cancer treatment and prevention.

BACKGROUND: Chemotherapy for malignant tumors can cause brain changes and cognitive impairment, leading to chemotherapy-induced cognitive impairment (CICI). Current research on CICI has focused on breast cancer and Hodgkin\'s lymphoma. Whether patients with non-Hodgkin\'s lymphoma (NHL) undergoing chemotherapy have cognitive impairment has not been fully investigated.
OBJECTIVE: To investigate whether NHL patients undergoing chemotherapy had cognitive impairments.
METHODS: The study included 100 NHL patients who were required to complete a comprehensive psychological scale including the Brief Psychiatric Examination Scale (MMSE) at two time points: before chemotherapy and within 2 wk of two chemotherapy courses. A language proficiency test (VFT), Symbol Number Pattern Test (SDMT), Clock Drawing Test (CDT), Abbreviated Daily Cognition Scale (ECog-12), Prospective and Retrospective Memory Questionnaire, and Karnofsky Performance Status were used to assess cognitive changes before and after chemotherapy.
RESULTS: The VFT scores for before treatment (BT) and after treatment (AT) groups were 45.20 ± 15.62, and 42.30 ± 17.53, respectively (t -2.16, P < 0.05). The CDT scores were 8 (3.5-9.25) for BT and 7 (2.5-9) for AT groups (Z -2.1, P < 0.05). Retrospective memory scores were 13.5 (9-17) for BT and 15 (13-18) for AT (Z -3.7, P < 0.01). The prospective memory scores were 12.63 ± 3.61 for BT and 14.43 ± 4.32 for AT groups (t -4.97, P < 0.01). The ECog-12 scores were 1.71 (1.25-2.08) for BT and 1.79 (1.42-2.08) for AT groups (Z -2.84, P < 0.01). The SDMT and MMSE values did not show a significant difference between BT and AT groups.
CONCLUSIONS: Compared to the AT group, the BT group showed impaired language, memory, and subjective cognition, but objective cognition and execution were not significantly affected.

Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression. Healthy adults aged 65 or older were randomized in a 1:1:1:1 ratio to receive a single injection of VAX-24 at 1 of 3 dose levels (1.1, 2.2, or a mixed dose of 2.2 or 4.4 mcg) or Prevnar 20® (PCV20) in a phase 2, blinded study. Primary outcome measures were solicited local and systemic events within 7 days post-vaccination, unsolicited adverse events (AEs) within 1 month, and serious AEs, medically attended AEs, or new onset of chronic disease within 6 months of vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) were measured pre-vaccination and at 1 month post-vaccination. Of 207 participants enrolled, 200 completed the trial. Safety profiles were comparable across the three VAX-24 doses and PCV20. Robust OPA and IgG immune responses were seen for all 24 serotypes. On average, immune responses to VAX-24 2.2 mcg dose were similar or higher compared to PCV20. In adults ≥ 65 years, VAX-24 had a safety profile similar to PCV20 through six months post-vaccination and induced robust OPA and IgG responses to all 24 serotypes, supporting prior data showing that site-specific conjugation allows for increased serotype coverage with similar or higher immune response vs other PCVs. The outcome of this phase 2 study further supports use of VAX-24 2.2 mcg dose in phase 3 trials. Clinicaltrials.gov: NCT05297578.

UNASSIGNED: Bidirectional Mendelian randomization (MR) combined with clinical case analysis was used to elucidate the relationship between generalized anxiety disorder (GAD) caused by mental overload and the risk of weight-bearing joint (hip/knee) osteoarthritis (OA).
UNASSIGNED: We performed MR analyses using publicly released genome-wide association study summary statistics to measure the causal effects between mental overload and weight-bearing joint OA risk. The primary MR analysis utilized the inverse-variance weighted (IVW) method, complemented by additional methods, including simple mode, weighted mode, MR-Egger regression, and weighted median. The leave-one-out method was used for sensitivity analysis. Concurrently, data from patients with OA (Kellgren-Lawrence grades III-IV) who needed total knee/hip arthroplasty were collected. Patient assessments were conducted utilizing the Western Ontario and McMaster Universities arthritis index, Penn State worry questionnaire, and visual analogue scale.
UNASSIGNED: Genetically predisposed GAD did not correlate with the risk of weight-bearing joint OA (IVW odds ratio [OR] = 0.840, 95 % confidence interval = 0.128, 5.50, P = 0.855). In reverse MR analyses, we detected no causal effect of weight-bearing OA on GAD (IVW OR = 1.00, 95 % CI = 0.985, 1.03, P = 0.687). In the clinical case evaluation, weight overload joint OA and GAD were highly correlated.
UNASSIGNED: MR analysis indicated no bidirectional causal effect of GAD caused by mental overload on weight-bearing joint (hip or knee) OA. Clinical studies support the finding that GAD is highly correlated with weight-bearing joint OA. However, whether there is a causal relationship between GAD caused by mental overload and weight-overloading joint OA requires further investigation.

The aim of this study is to investigate the correlation between the incidence of spontaneous tumours of various origins and the localisation in dogs with sex, breed, and age factors. A total of 360 tumours with various localisation were studied pathomorphologically. Histopathologic data sets from 360 dog tissue samples were processed and statistically examined. A chi-square test of independence was conducted to examine the relationships among the various levels of the specified variables. Logistic regression models were employed for dichotomous outcomes to ascertain the influence of certain explanatory variables on the tumour types. Characteristic pathomorphological changes observed during examination of dogs with oncologic diseases were determined. The most common neoplasms were mammary tumours, accounting for 43% of the cases. The mammary gland tumours were most common in mongrel dogs (25%), with German Shepherds (17.3%), Poodles, Dachshunds, Central Asian Shepherds (6.7% each), and Rottweilers (5.7%) following. The highest frequency of these tumours appeared at 8 years of age, predominantly originating from the ductal epithelium, which represented 46.4% of all the malignant cases.

BACKGROUND: Our search for plant-derived ceramides from sustainable sources led to the discovery of ceramides and glucosylceramides in wine lees.
OBJECTIVE: This study evaluated the efficacy and safety of wine lees extract (WLE)-derived ceramides and glucosylceramides in enhancing skin barrier function.
METHODS: A randomized, double-blind, placebo-controlled study was conducted with 30 healthy Japanese subjects aged 20-64. Subjects were allocated to receive either the WLE-derived ceramides and glucosylceramides (test group) or placebo for 12 weeks. The primary outcome was transepidermal water loss (TEWL), and secondary outcomes included skin hydration, visual analog scale (VAS) of itching sensation, and the Japanese Skindex-29.
RESULTS: One participant withdrew for personal reasons, resulting in 29 subjects for data analysis (placebo n = 15; test n = 14). The test group showed a tendency of lower TEWL compared to the placebo after 8 weeks (p = 0.07). Furthermore, after 12 weeks of administration, the test group had significantly lower TEWL than the placebo (p = 0.04). On the other hand, no significant differences were observed in the secondary outcome parameters. No adverse events related to the supplements were reported.
CONCLUSIONS: Oral supplementation of WLE-derived ceramides and glucosylceramides is a prominent and safe approach to enhancing skin barrier function and health.
BACKGROUND: (UMIN000050422).

Deficits in N-methyl-d-aspartate receptor (NMDAR) signaling are implicated in the pathogenesis of schizophrenia. Luvadaxistat (TAK-831/NBI-1065844) is an investigational d-amino acid oxidase (DAAO) inhibitor that increases d-serine levels at NMDAR coagonist sites. INTERACT is a phase 2 randomized, placebo-controlled study that evaluated the efficacy and safety of three doses of luvadaxistat, covering a range of DAAO occupancy and d-serine levels, in patients with schizophrenia with persistent negative symptoms. The study included a 14-day, single-blinded placebo run-in period and a 12-week, double-blinded treatment period. The primary efficacy endpoint was the 12-week change from baseline in Positive and Negative Syndrome Scale-Negative Symptom Factor Score (PANSS NSFS). Secondary efficacy endpoints included the 12-week changes from baseline in Brief Assessment of Cognition in Schizophrenia (BACS) score and Schizophrenia Cognition Rating Scale (SCoRS) score. Safety endpoints included adverse event assessments. The full analysis set included all randomized patients (N = 256 [placebo, n = 87; luvadaxistat 50 mg, n = 58; 125 mg, n = 56; 500 mg, n = 55]); 228 patients completed the study. No significant improvements in PANSS NSFS were observed at any dose versus placebo at week 12. Improvements were observed with luvadaxistat 50 mg versus placebo in cognitive endpoints: BACS composite score (nominal one-sided p = 0.031) and SCoRS interviewer total score (nominal one-sided p = 0.011). Luvadaxistat did not significantly improve negative symptoms of schizophrenia. However, luvadaxistat 50 mg met the prespecified secondary endpoints for cognitive performance (BACS) and function (SCoRS), warranting further investigation in patients with cognitive impairment associated with schizophrenia. Luvadaxistat was well-tolerated in INTERACT, with no new safety signals observed. ClinicalTrials.gov: NCT03382639.