Patient Samples Research Articles

Alpha-1-Acid Glycoprotein Quantification via Spatial Proximity Analyte Reagent Capture Luminescence Assay: Application as Diagnostic and Prognostic Marker in Serum and Effusions of Cats with Feline Infectious Peritonitis Undergoing GS-441524 Therapy

Until recently, the diagnosis of feline infectious peritonitis (FIP) in cats usually led to euthanasia, but recent research has revealed that antiviral drugs, including the nucleoside analog GS-441524, have the potential to effectively cure FIP. Alpha-1-acid glycoprotein (AGP) has been suggested as a diagnostic marker for FIP. However, AGP quantification methods are not easily accessible. This study aimed to establish a Spatial Proximity Analyte Reagent Capture Luminescence (SPARCLTM) assay on the VetBio-1 analyzer to determine the AGP concentrations in feline serum and effusion samples. Linearity was found in serial dilutions between 1:2000 and 1:32,000; the intra-run and inter-run precision was <5% and <15%, respectively; and AGP was stable in serum stored for at least 8 days at room temperature, at 4 °C and at −20 °C. Cats with confirmed FIP had significantly higher serum AGP concentrations (median: 2954 µg/mL (range: 200–5861 µg/mL)) than those with other inflammatory diseases (median: 1734 µg/mL (305–3449 µg/mL)) and clinically healthy cats (median 235 µg/mL (range: 78–616 µg/mL); pKW < 0.0001). The AGP concentrations were significantly higher in the effusions from cats with FIP than in those from diseased cats without FIP (pMWU < 0.0001). The AGP concentrations in the serum of cats with FIP undergoing GS-441524 treatment showed a significant drop within the first seven days of treatment and reached normal levels after ~14 days. In conclusion, the VetBio-1 SPARCLTM assay offers a precise, fast and cost-effective method to measure the AGP concentrations in serum and effusion samples of feline patients. The monitoring of the AGP concentration throughout FIP treatment provides a valuable marker to evaluate the treatment’s effectiveness and identify potential relapses at an early stage.

Molecular analysis for ovarian cancer detection in patient-friendly samples

BackgroundHigh ovarian cancer mortality rates motivate the development of effective and patient-friendly diagnostics. Here, we explored the potential of molecular testing in patient-friendly samples for ovarian cancer detection.MethodsHome-collected urine, cervicovaginal self-samples, and clinician-taken cervical scrapes were prospectively collected from 54 patients diagnosed with a highly suspicious ovarian mass (benign n = 25, malignant n = 29). All samples were tested for nine methylation markers, using quantitative methylation-specific PCRs that were verified on ovarian tissue samples, and compared to non-paired patient-friendly samples of 110 age-matched healthy controls. Copy number analysis was performed on a subset of urine samples of ovarian cancer patients by shallow whole-genome sequencing.ResultsThree methylation markers are significantly elevated in full void urine of ovarian cancer patients as compared to healthy controls (C2CD4D, P = 0.008; CDO1, P = 0.022; MAL, P = 0.008), of which two are also discriminatory in cervical scrapes (C2CD4D, P = 0.001; CDO1, P = 0.004). When comparing benign and malignant ovarian masses, GHSR shows significantly elevated methylation levels in the urine sediment of ovarian cancer patients (P = 0.024). Other methylation markers demonstrate comparably high methylation levels in benign and malignant ovarian masses. Cervicovaginal self-samples show no elevated methylation levels in patients with ovarian masses as compared to healthy controls. Copy number changes are identified in 4 out of 23 urine samples of ovarian cancer patients.ConclusionsOur study reveals increased methylation levels of ovarian cancer-associated genes and copy number aberrations in the urine of ovarian cancer patients. Our findings support continued research into urine biomarkers for ovarian cancer detection and highlight the importance of including benign ovarian masses in future studies to develop a clinically useful test.

Detection and Quantification of Human Herpes Viruses Types-6 and Cytomegaly Viruses in Sperm Samples of Patients with Fertility Disorders

Background; Viral infections are common around the world and cause many health problems. Infertility in men is a widespread health problem that can affect lifestyle and psychological state. Aims of the study; Study of the effect of herpes virus type 6 and cytomegalovirus on infertility disorders in men. Methodology; A case control study was done for a 100 specimens collected from men. This study has been conducted in Al Sader Medical City / Infertility Center / Al-Najaf Al-Ashraf and privet Center Dr. Ali Al-Ibrahimi for Embryos and Infertility in najaf . During the period from 10/10/ 2023 to 10/4/2024. The current study consisted of a sample size of 100 males, which was subsequently separated into two groups. The control group comprised 40 fertile men, aged 25 to 45 years, who had experienced both primary and secondary fecundity for at least twelve months. The Patients Cases group, consisting of sixty infertile males aged between 22 and 46 years, was categorized into two subgroups based on the type of infertility. There were forty-six guys who were classified as main infertility. There were a total of fourteen men who experienced secondary infertility. Male participants who are reproductive age, normal seminal analysis which is healthy and have a child as a Control group (Fertile men). Name of patient, sample number, Age (years), Education, housing area, Type of work, height, weight, Smoking, chronic diseases, History of surgery, Primary infertility, Secondary infertility, Sperm count, Sperm motility and Sperm morphology. Detection of CMV in semen plasma by CMV ELISA kit and detection of HHV 6 in semen plasma by HHV 6 ELISA kit. Result; The results showed that there was no statistical significance in age between the two groups. They also showed that there was statistical significance in smoking, type of infertility, and duration of infertility. The results showed statistical significance in the results for herpes and cytomegalovirus. There is also no statistical significance regarding the number of cases of cytomegalovirus infection according to age. On the contrary, there was statistical significance regarding age in herpes. The results also indicated that there was statistical evidence in the sperm analysis between the two groups. Conclusions; The statistical evidence between the two groups in the number of infection cases for all groups or by age indicates the role of viral infections in causing infertility in men.

Retrospective Data Analysis Reveals Unusual Metabolism Pattern of Ethanol in Pediatrics as Compared to Adult and Geriatric Populations.

About 95% of consumed ethanol is metabolized by oxidative pathways. Less than 1% is metabolized via nonoxidative pathways: glucuronidation, sulfation, and the formation of fatty acid esters of ethanol. In neonates, the glucuronidation pathway has been reported to be underdeveloped but matures with age. This work compared the test results of patients' random urine samples submitted to our facility for ethyl glucuronide (EtG) and ethyl sulfate (EtS) measurements across pediatric and adult populations. Test results (n = 63 498) from urine samples tested for EtG and EtS by quantitative liquid chromatography-tandem mass spectrometry at our facility were utilized for this study. EtG and EtS concentrations were compared across the age partitions 0 to 17 years (pediatric), 18 to 80 years (adult), and 81 to 100 years (geriatric). Eight pediatric patients from a tertiary academic hospital contributed clinical context via abstracted clinical information. Across the individual age partitions, 60% to 65% of patients had both EtG and EtS present in urine. Approximately 5% to 10% of patients had only EtG, and 25% to 35% had neither metabolite present. The lowest percentages (<1.5%) had EtS present in the absence of EtG. Markedly, no pediatric patients had only EtS present; compared to the adult population, this was statistically significant (Fisher exact test, P = 0.025). From the data presented in this work, EtG is more prevalent relative to EtS in urine samples of patients assessed for ethanol exposure.

Enhanced patient-based real-time quality control using the graph-based anomaly detection.

Patient-based real-time quality control (PBRTQC) is an alternative tool for laboratories that has gained increasing attention. Despite the progress made by using various algorithms, the problems of data volume imbalance between in-control and out-of-control results, as well as the issue of variation remain challenges. We propose a novel integrated framework using anomaly detection and graph neural network, combining clinical variables and statistical algorithms, to improve the error detection performance of patient-based quality control. The testing results of three representative analytes (sodium, potassium, and calcium) and eight independent variables of patients (test date, time, gender, age, department, patient type, and reference interval limits) were collected. Graph-based anomaly detection network was modeled and used to generate control limits. Proportional and random errors were simulated for performance evaluation. Five mainstream PBRTQC statistical algorithms were chosen for comparison. The framework of a patient-based graph anomaly detection network for real-time quality control (PGADQC) was established and proven feasible for error detection. Compared with classic PBRTQC, the PGADQC showed a more balanced performance for both positive and negative biases. For different analytes, the average number of patient samples until error detection (ANPed) of PGADQC decreased variably, and reductions could reach up to approximately 95 % at a small bias of 0.02 taking calcium as an example. The PGADQC is an effective framework for patient-based quality control, integrating statistical and artificial intelligence algorithms. It improves error detection in a data-driven fashion and provides a new approach for PBRTQC from the data science perspective.

Organic Nanoparticles in Progressing Cardiovascular Disease Treatment and Diagnosis

Cardiovascular diseases (CVDs), the world’s most prominent cause of mortality, continue to be challenging conditions for patients, physicians, and researchers alike. CVDs comprise a wide range of illnesses affecting the heart, blood vessels, and the blood that flows through and between them. Advances in nanomedicine, a discipline focused on improving patient outcomes through revolutionary treatments, imaging agents, and ex vivo diagnostics, have created enthusiasm for overcoming limitations in CVDs’ therapeutic and diagnostic landscapes. Nanomedicine can be involved in clinical purposes for CVD through the augmentation of cardiac or heart-related biomaterials, which can be functionally, mechanically, immunologically, and electrically improved by incorporating nanomaterials; vasculature applications, which involve systemically injected nanotherapeutics and imaging nanodiagnostics, nano-enabled biomaterials, or tissue-nanoengineered solutions; and enhancement of sensitivity and/or specificity of ex vivo diagnostic devices for patient samples. Therefore, this review discusses the latest studies based on applying organic nanoparticles in cardiovascular illness, including drug-conjugated polymers, lipid nanoparticles, and micelles. Following the revised information, it can be concluded that organic nanoparticles may be the most appropriate type of treatment for cardiovascular diseases due to their biocompatibility and capacity to integrate various drugs.

Assessment of Urinary Tract Infections Among Female Patients Attending Ruhengeri Referral Hospital

Background: Urinary tract infections (UTIs) are the inflammatory disorders of the urinary tract caused by the abnormal growth of pathogens. UTI is known to cause short-term morbidity in terms of fever, dysuria, and lower abdominal pain (LAP) and may result in permanent scarring of the kidney. The presence of bacteria in the urine, known as bacteriuria, may be indicative of infection or colonization of the urinary tract, but it may also be due to bacterial contamination occurring during collection of a specimen. Aim: The present study was done in order to identify the bacteria causing UTI from female patients. Methodology: A cross sectional study was conducted on female patients who were attending Ruhengeri Referral Hospital in a period of two months from October to November 2021. Urine samples were collected from patients who were requested to urinary test with respect to standard procedures. Samples were processed and analyzed at INES-Ruhengeri microbiology laboratory where gram stain and culture as well as biochemical test were performed in order to make microbial identification. From the results patients who were found with UTI, their structured questionnaire was taken into consideration in order to determine the associated risk factors. Results: The outcomes of the study indicated that E.coli, K. pneumonia, P. aeruginosa, Enterobacter ssp and S. saprophyticus were isolated from patients urine sample where E. coli is more present in patients sample where it has been found at 60%(18) samples. The least isolated bacteria in patient’s samples are Enterrobacter spp and S. saprophyticus at frequency of 2(6.7) per each bacterium. The risk factor associated with urinary tract infection in female patients attended Ruhengeri-referral-hospital in a period of study, the results indicated that douching in secret parts twice a day is associated with UTI with P-value equivalent to 0.001. Conclusion: This study was intended to assess the UTI among female patients. The study findings indicated that E.coli, K. pneumonia, P. aeruginosa, Enterobacter ssp and S. saprophyticus are more likely to be found in urinary tract of female. The study finding has indicated also that poor hygienic life style increases the risk of being infected by UTIs.

Distinct Expression Profiles of Neuroblastoma-Associated mRNAs in Peripheral Blood and Bone Marrow of Non-High-Risk and High-Risk Neuroblastoma Patients.

Non-high-risk (non-HR) neuroblastoma (NB) patients have excellent outcomes, with more than a 90% survival rate, whereas HR NB patients expect less than a 50% survival rate. Metastatic disease is the principal cause of death among both non-HR and HR NB patients. Previous studies have reported the significant but limited prognostic value of quantitative PCR (qPCR)-based assays, measuring overlapping but different sets of neuroblastoma-associated mRNAs (NB-mRNAs), to detect metastatic disease in both non-HR and HR patient samples. A droplet digital PCR (ddPCR)-based assay measuring seven NB-mRNAs (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs) was recently developed and exhibited a better prognostic value for HR patient samples than qPCR-based assays. However, it remained to be tested on non-HR patient samples. In the present study, we employed the ddPCR-based assay to study peripheral blood (PB) and bone marrow (BM) samples collected at diagnosis from eight non-HR and eleven HR cases and characterized the expression profiles of NB-mRNAs. The most highly expressed NB-mRNAs in PB and BM differed between non-HR and HR cases, with the CRMP1 mRNA being predominant in non-HR cases and the GAP43 mRNA in HR cases. The levels of NB-mRNAs in PB and BM were 5 to 1000 times lower in non-HR cases than in HR cases. The PB to BM ratio of NB-mRNAs was 10 to 100 times higher in non-HR cases compared to HR cases. The present case series suggests that non-HR and HR NB patients have the distinct expression profiles of NB-mRNAs in their PB and BM.

Long non-coding RNA TUG1 is down-regulated in Friedreich’s ataxia

Abstract Friedreich's Ataxia (FRDA) is a neurodegenerative disorder caused by reduced frataxin (FXN) levels. It leads to motor and sensory impairments and has a median life expectancy of around 35 years. As the most common inherited form of ataxia, FRDA lacks reliable, non-invasive biomarkers, prolonging and inflating the cost of clinical trials. This study proposes TUG1, a long non-coding RNA, as a promising blood-based biomarker for FRDA, which is known to regulate various cellular processes. In a previous study using a frataxin knockdown mouse model, we observed several hallmark FRDA symptoms. Building on this, we hypothesized that a dual-source approach—comparing the data from peripheral blood samples from FRDA patients with tissue samples from affected areas in FRDA knockdown mice, tissues usually unattainable from patients—would effectively identify robust biomarkers. A comprehensive reanalysis was conducted on gene expression data from 183 age- and sex-matched peripheral blood samples of FRDA patients, carriers, and controls, and 192 tissue datasets from FRDA knockdown mice. Blood and tissue samples underwent RNA isolation and quantitative reverse transcription PCR, and frataxin knockdown was confirmed through ELISA. Tug1 RNA interaction was explored via RNA pull-down assays. Validation was performed in serum samples on an independent set of 45 controls and 45 FRDA patients, and in blood samples from 66 heterozygous carriers and 72 FRDA patients. Tug1 and Slc40a1 emerged as potential blood-based biomarkers, confirmed in the FRDA knockdown mouse model (One-way ANOVA, p ≤ 0.05). Tug1 was consistently downregulated after Fxn knockdown and correlated strongly with Fxn levels (R2 = 0.71 during depletion, R2 = 0.74 during rescue). Slc40a1 showed a similar but tissue-specific pattern. Further validation of Tug1's downstream targets strengthened its biomarker candidacy. In additional human samples, TUG1 levels were significantly downregulated in both whole blood and serum of FRDA patients compared to controls (Wilcoxon signed-rank test, p &amp;lt; 0.05). Regression analyses revealed a negative correlation between TUG1 fold-change and disease onset (p &amp;lt; 0.0037), and positive correlations with disease duration and Functional Disability Stage score (p &amp;lt; 0.04). This suggests that elevated TUG1 levels correlate with earlier onset and more severe cases. This study identifies TUG1 as a potential blood-based biomarker for FRDA, showing consistent expression variance in human and mouse tissues related to disease severity and key FRDA pathways. It correlates with frataxin levels, indicating its promise as an early, non-invasive marker. TUG1 holds potential for FRDA monitoring and therapeutic development, meriting additional research.

Hydrogen Sulfide-Induced Activatable Photodynamic Therapy Adjunct to Disruption of Subcellular Glycolysis in Cancer Cells by a Fluorescence-SERS Bimodal Iridium Metal-Organic Hybrid.

The practical application of photodynamic therapy (PDT) demands targeted and activatable photosensitizers to mitigate off-target phototoxicity common in "always on" photosensitizers during light exposure. Herein, a cyclometalated iridium complex-based activatable photodynamic molecular hybrid, Cy-Ir-7-nitrobenzofurazan (NBD), is demonstrated as a biomedicine for molecular precision. This design integrates a hydrogen sulfide (H2S)-responsive NBD unit with a hydroxy-appended iridium complex, Cy-Ir-OH. In normal physiological conditions, the electron-rich Ir metal center exerts electron transfer to the NBD unit, quenches the excited state dynamics, and establishes a PDT-off state. Upon exposure to H2S, Cy-Ir-NBD activates into the potent photosensitizer Cy-Ir-OH through nucleophilic substitution. This mechanism ensures exceptional specificity, enabling targeted phototherapy in H2S-rich cancer cells. Additionally, we observed that Cy-Ir-NBD-induced H2S depletion disrupts S-sulfhydration of the glyceraldehyde-3-phosphate dehydrogenase enzyme, impairing glycolysis and ATP production in the cellular milieu. This sequential therapeutic process of Cy-Ir-NBD is governed by the positively charged central iridium ion that ensures mitochondria-mediated apoptosis in cancer cells. Dual-modality SERS and fluorescence imaging validate apoptotic events, highlighting Cy-Ir-NBD as an advanced theranostic molecular entity for activatable PDT. Finally, as a proof of concept, clinical assessment is evaluated with the blood samples of breast cancer patients and healthy volunteers, based on their H2S overexpression capability through SERS and fluorescence, revealing Cy-Ir-NBD to be a promising predictor for PDT activation in advanced cancer phototherapy.

Pro-inflammatory cytokine alterations in recent onset anorexia nervosa adolescent female patients before and after 6 months of integrated therapy: A case-control study.

Anorexia nervosa (AN) is a complex disorder affecting mainly, but not only, teenagers. Researchers agree that AN is deeply associated with a pro-inflammatory state following an impaired immune system, resulting from altered levels of cytokines such as IL-1β and TNF-α, also impacted by the frequent depressive states. Thus, this case-control study aimed to evaluate the relationship between patients suffering from AN undergoing specialized eating disorder treatment for AN and pro-inflammatory cytokines. To reach our purpose, we assessed eating-related psychopathology and depressive symptoms and measured serum concentration of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α before and after 6 months of integrated therapy (which included psychopharmacotherapy, psychotherapy, and nutritional treatment), to define whether selected pro-inflammatory cytokines could be considered a pathophysiological marker of the disorder. A sample of 16 young female patients with early diagnosis of AN, and without any previous treatment, and 22 healthy controls matched by age, sex, and socioeconomic status were enrolled. After 6 months of integrated therapy, a significant decrease of all selected pro-inflammatory cytokines was detected. In addition, an improvement in the anxiety-depressant aspects was also noted. In conclusion, the results obtained suggest that pro-inflammatory cytokines are indeed related to the pathophysiology of AN. However, further investigations, involving larger samples of patients with distinct subtypes of AN, are essential to confirm the current findings.

Longitudinal Analysis and Latent Growth Modeling of the Modified Hip Dysfunction and Osteoarthritis Outcome Score for Joint Replacement (HOOS-JR).

The Hip Dysfunction and Osteoarthritis Outcome Score for Joint Replacement (HOOS-JR) was developed as a short-form survey to measure progress after total hip arthroplasty (THA). However, the longitudinal validity of the scale structure pertaining to the modified five-item HOOS-JR has not been assessed. Therefore, the purpose of this study was to evaluate the structural validity, longitudinal invariance properties, and latent growth curve (LGC) modeling of the modified five-item HOOS-JR in a large multi-site sample of patients who underwent a THA. A longitudinal study was conducted using data from the Surgical Outcome System (SOS) database. Confirmatory factor analyses (CFAs) were conducted to assess the structural validity and longitudinal invariance across five time points. Additionally, LGC modeling was performed to assess the heterogeneity of the recovery patterns for different subgroups of patients. The resulting CFAs met most of the goodness-of-fit indices (CFI = 0.964-0.982; IFI = 0.965-0.986; SRMR = 0.021-0.035). Longitudinal analysis did not meet full invariance, exceeding the scalar invariance model (CFIDIFF = 0.012; χ2DIFF test = 702.67). Partial invariance requirements were met upon release of the intercept constraint associated with item five (CFIDIFF test = 0.010; χ2DIFF = 1073.83). The equal means model did not pass the recommended goodness-of-fit indices (CFIDIFF = 0.133; χ2DIFF = 3962.49). Scores significantly changed over time, with the highest scores identified preoperatively and the lowest scores identified at 2- and 3-years postoperatively. Upon conclusion, partial scalar invariance was identified within our model. We identified that patients self-report most improvements in their scores within 6 months postoperatively. Females reported more hip disability at preoperative time points and had faster improvement as measured by the scores of the modified five-item HOOS-JR.

Total knee arthroplasty survival rates are lower in younger men,as well as rheumatoid patients and after previous high-tibial osteotomy: A registry study.

The purpose of this study was to investigate if patient's gender significantly affected the long-term outcome of patients undergoing total knee arthroplasty (TKA) and to provide a cross-gender comparison of a large patient sample from a single regional register. The Registry of Prosthetic Orthopedic Implant of Emilia Romagna (RIPO) investigated all primary TKAs performed from July 2000 to December 2020 by collecting data of menand womenseparately. Primary bicompartmental and tricompartmental TKAs were included. The survival rates and the reasons for revision were assessed to check if any other factor could have influenced implantfailure. In total,66,032 TKAs were included and analysed, comprising 46,774 women and 19,258 men. The 15-year Kaplan-Meier survival percentage was 93.6% for womenand 92.5% formen (p = 0.001). Men exhibited a higher revision risk following primary TKA(p = 0.012), particularly when the primary diagnosis was arthritis resulting from rheumatic disorders (p = 0.018) and arthritis following high-tibial osteotomy (p = 0.024). Failure risk was also higher for men below the age of 60 years(p = 0.038). The long-term outcome in TKA showed significant differences between men and women, with a significantly lower survival rate in men at 15 years, especially when they areunder 60 years old or with a diagnosis of rheumatic disorders or arthritis following high-tibial osteotomy. It is necessary to design specific studies to have relevant data concerning gender differences in prosthetic surgery and to customise treatments to improve outcome and patient satisfaction. Level III.

The Impact of Palliative Care Consultation on Aggressive Medical Interventions in End-of-life Among Patients with Metastatic Breast Cancer: Insights from the U.S. National Patient Sample.

Advancement in treatment has led to prolonged survival and a rising number of women living with metastatic breast cancer (MBC) in the United States. Due to its high symptom burden, it is recommended that palliative care be integrated into the standard care to help improve quality of life. However, little is known about the use of palliative care among MBC patients in the nation. To determine utilization of palliative care consult (PCC) after metastasis and the influence of PCC on healthcare utilization in the end of life among women living with MBC in the US. This retrospective cohort study examined a national electronic health record database to quantify the PCC use after metastasis diagnosis until death and the associations of PCC with Emergency Department (ED), Intensive Care Unit (ICU), and chemotherapies in the end-of-life women (age ≥ 18 years) living with MBC. From a cohort of 2615 deceased MBC patients, 37% received PCC in the last 6 months of life. Patients who had received PCC in the end-of-life were more likely to be hospitalized, admitted to ED and ICU, and receive chemotherapies in the last 60 days before death. However, patients who had received end-of-life PCC had less hospital and ED visits and received less chemotherapies after PCC initiated. While PCC can reduce end-of-life aggressive interventions, it was underutilized among patients with MBC in the end-of-life. A myriad of clinical and patient factors may still challenge timely consultation. We urge for future endeavors in developing strategies to remove barriers in the implementation, especially earlier in the disease course, to assure timely PC treatments and reduce discomfort amid aggressive interventions for MBC.

The impact of diabetes status on pain and physical function following total joint arthroplasty for hip and knee osteoarthritis: variation by sex and body mass index

Few studies have examined diabetes impact on total joint arthroplasty (TJA) outcomes, with variable findings. We investigated the association between diabetes and post-TJA physical function and pain, examining whether diabetes impact differs by sex and BMI. Patient sample completed questionnaires within 3 months prior to hip or knee TJA for osteoarthritis (OA) and 1-year post-surgery. Surgical ‘non-response’ was defined as < 30% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function at 1-year. Two adjusted logistic regression models were estimated: (1) excluding, (2) including an interaction between diabetes, sex and BMI. The sample (626 hip, 754 knee) was 54.9% female, had mean BMI of 30.1, 13.0% reported diabetes. In adjusted models excluding an interaction, diabetes was not associated with non-response. However, a significant 3-way interaction (physical function: p = 0.003; pain: p = 0.006) between diabetes, sex, and BMI was found and was associated with non-response: non-response probability increased with increasing BMI in men with diabetes, but decreased with increasing BMI in women in diabetes. Findings suggest uncertainty in diabetes impact may be due to differential impacts by sex and BMI. A simple consideration of diabetes as present vs. absent may not be sufficient, with implications for the large TJA population.

Peri-implant diseases and systemic inflammation: A preliminary analysis from a cross-sectional survey of patients with hypertension.

The aim of this study was to investigate the association between peri-implant diseases and systemic inflammation assessed by serum C-reactive protein (CRP) levels in a sample of patients with hypertension. A total of 151 participants with hypertension were included in a cross-sectional study. The population was divided into six groups according to their peri-implant and periodontal status (healthy controls, mucositis, peri-implantitis, periodontitis, periodontitis and mucositis, periodontitis, and peri-implantitis). Linear, logistic regression, and correlation analyses were performed. CRP levels were statistically significantly higher in participants with periodontitis alone (median 3.2mg/L, interquartile range [IQR] 1.8, p=0.012), combined with mucositis (3.10mg/L, IQR 2.35, p<0.001) or peri-implantitis (2.7mg/L, IQR 2.53, p=0.002) when compared to the healthy controls (1mg/L, IQR 1.2). This association was independent of age, sex, smoking status, and adiposity differences. Participants with periodontitis with and without peri-implant diseases had the greatest odds of exhibiting CRP>3mg/L (odds ratio=7.3, 95% confidence interval 1.6-33.9). Peri-implant diseases are associated with systemic inflammation, but the nature of the association should be further investigated.

Hotspot DNA Methyltransferase 3A (DNMT3A) and Isocitrate Dehydrogenase 1 and 2 (IDH1/2) Mutations in Acute Myeloid Leukemia and Their Relevance as Targets for Immunotherapy.

DNA methyltransferase 3A (DNMT3A) and isocitrate dehydrogenase 1 and 2 (IDH1/2) are genes involved in epigenetic regulation, each mutated in 7-23% of patients with acute myeloid leukemia. Here, we investigated whether hotspot mutations in these genes encode neoantigens that can be targeted by immunotherapy. Five human B-lymphoblastoid cell lines expressing common HLA class I alleles were transduced with a minigene construct containing mutations that often occur in DNMT3A or IDH1/2. From these minigene-transduced cell lines, peptides were eluted from HLA class I alleles and analyzed using tandem mass spectrometry. The resulting data are available via ProteomeXchange under the identifier PXD050560. Mass spectrometry revealed an HLA-A*01:01-binding DNMT3AR882H peptide and an HLA-B*07:02-binding IDH2R140Q peptide as potential neoantigens. For these neopeptides, peptide-HLA tetramers were produced to search for specific T-cells in healthy individuals. Various T-cell clones were isolated showing specific reactivity against cell lines transduced with full-length DNMT3AR882H or IDH2R140Q genes, while cell lines transduced with wildtype genes were not recognized. One T-cell clone for DNMT3AR882H also reacted against patient-derived acute myeloid leukemia cells with the mutation, while patient samples without the mutation were not recognized, thereby validating the surface presentation of a DNMT3AR882H neoantigen that can potentially be targeted in acute myeloid leukemia via immunotherapy.

Prevalence, sociodemographic, and clinical correlates of underweight in a sample of Chinese male alcohol-dependent patients.

Underweight is a significant symptom in alcohol-dependent patients, yet few studies have examined underweight in Chinese male patients. The current study aimed to identify the prevalence, sociodemographic, and clinical correlates of underweight in Chinese male patients with alcohol dependency. In this cross-sectional study, 405 male inpatients with alcohol dependence and 383 healthy male controls were recruited. Participants' demographic and clinical data, including anthropometric data, were collected. We first conducted univariate analysis to identify seven variables with significant differences between groups: smoking behavior, hospitalization, alcohol consumption, cerebral infarction, hypertension, Hamilton Depression Scale (HAMD) score, and Scale for Assessment of Negative Symptom (SANS) score. Then, binary logistic regression was used to assess their relationship with underweight, with a significance level of .05. The prevalence of underweight was significantly higher in the study population than in the control group (2.99% vs. 2.87%; P < .001). Patients with underweight had significantly higher rates of smoking behavior and cerebral infarction, as well as higher scores of SANS and HAMD than non-underweight patients. The non-underweight patients had higher daily alcohol consumption and times of hospitalization. Furthermore, logistic regression analysis showed that smoking behavior [odds ratio (OR) = 2.84, 95% confidence interval (CI) = 1.03-7.80, P = .043)], cerebral infarction (OR = 5.20, 95% CI = 1.13-23.85, P = .036), SANS score (OR = 1.22, 95% CI = 1.16-1.28, P < .001), and HAMD score (OR = 1.06, 95% CI = 1.02-1.11, P = .005) were associated with underweight. More than 20% of male alcohol-dependent patients in a Chinese sample were underweight. Some demographic and clinical variables independent correlates for underweight in alcohol-dependent patients. We need to focus on alcohol-dependent patients with smoking, cerebral infarction, depression, and more prominent negative symptoms.

Nucleoporin 93 Regulates Cancer Cell Growth and Stemness in Bladder Cancer via Wnt/β-Catenin Signaling.

Bladder cancer (BLCA) is a prevalent cancer type with an unmet need for new therapeutic strategies. Nucleoporin 93 (Nup93) is implicated in the pathophysiology of several cancers, but its relationship with bladder cancer remains unclear. Nup93 expression was analyzed in TCGA datasets and 88 BLCA patient samples. Survival analysis and Cox regression models evaluated the association between Nup93 levels and patient prognosis. BLCA cells were used to investigate the effects of Nup93 overexpression or knockdown on cell growth, invasion, stemness (sphere formation and ALDH2 + cancer stem cell marker), and Wnt/β-catenin signaling in vitro. The Wnt activator BML-284 was used to confirm the involvement of Wnt/β-catenin signaling pathway. A xenograft mouse model validated the in vitro findings. Nup93 was highly expressed in BLCA tissues and cell lines, and high Nup93 expression correlated with poor prognosis in BLCA patients. Nup93 silencing inhibited BLCA cell proliferation, Wnt/β-catenin activation, and cancer cell stemness. Conversely, Nup93 overexpression promoted these effects. BML-284 partially rescued the reduction in cell growth and stemness markers caused by Nup93 knockdown. Nup93 knockdown also suppressed the tumor formation of BLCA cells in vivo. Nup93 regulates BLCA cell growth and stemness via the Wnt/β-catenin pathway, suggesting its potential as a prognostic marker and therapeutic target in BLCA.

Serological Evidence of Mpox Virus Infection During Peak Mpox Transmission in New York City, July to August 2022.

The extent to which infections may have been undetected in an epicenter of the 2022 mpox outbreak is unknown. A serosurvey (July and August 2022) assessed the seroprevalence and correlates of mpox infection among a diverse sample of asymptomatic patients with no prior mpox diagnoses and no known histories of smallpox or mpox vaccination. We present seropositivity stratified by participant characteristics collected via survey. Two-thirds of 419 participants were cismen (281 of 419), of whom 59.1% (166 of 281) reported sex with men (MSM). The sample also included 109 ciswomen and 28 transgender/gender nonconforming/nonbinary individuals. Overall seroprevalence was 6.4% (95% confidence interval [CI], 4.1%-8.8%); 3.7% among ciswomen (95% CI, 1.0%-9.1%), 7.0% among cismen with only ciswomen partners (95% CI, 2.0%-11.9%), and 7.8% among MSM (95% CI, 3.7%-11.9%). There was little variation in seroprevalence by race/ethnicity, age group, HIV status, or number of recent sex partners. No participants who reported close contact with mpox cases were seropositive. Among participants without recent mpox-like symptoms, 6.3% were seropositive (95% CI, 3.6%-9.0%). Approximately 1 in 15 vaccine-naive people in our study had antibodies to mpox during the height of the NYC outbreak, indicating the presence of asymptomatic infections that could contribute to ongoing transmission.