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There is great concern in equine sport over the potential use of pharmaceutical agents capable of editing the genome or modifying the expression of gene products. Synthetic oligonucleotides are short, single-stranded polynucleotides that represent a class of agents capable of modifying gene expression products with a high potential for abuse in horseracing. As these substances are not covered by most routine anti-doping analytical approaches, they represent an entire class of compounds that are not readily detectable. The nucleotide sequence for each oligonucleotide is highly specific, which makes targeted analysis for these agents problematic. Accordingly, we have developed a non-targeted approach to detect the presence of specific product ions that are not naturally present in ribonucleic acids. Briefly, serum samples were extracted using solid-phase extraction with a mixed-mode cartridge following the disruption of protein interactions to isolate the oligonucleotides. Following the elution and concentration steps, chromatographic separation was achieved utilizing reversed-phase liquid chromatography. Following an introduction to a Thermo Q Exactive HF mass spectrometer using electrospray ionization, analytes were detected utilizing a combination of full-scan, parallel reaction monitoring and all ion fragmentation scan modes. The limits of detection were determined along with the accuracy, precision, stability, recovery, and matrix effects using a representative 13mer oligonucleotide. Following method optimization using the 13mer oligonucleotide, the method was applied to successfully detect the presence of specific product ions in three unique oligonucleotide sequences targeting equine-specific transcripts.

Background: Human serum is a major component of Plasmodium falciparum culture medium, and can be replaced with AlbuMAX™ II, a lipid-rich bovine serum albumin, for asexual cultures. However, gametocytes produced without serum are poorly infective to mosquitoes. Serum suffers from high cost, limited availability, and variability in quality. Methods: Several commercially-available media supplements were tested for their ability to support parasite growth and production of P. falciparum (3D7) gametocytes in standard RPMI1640 medium containing 0.5% AlbuMAX. The impact on asexual growth and gametocyte production with each supplement was assessed and compared to standard RPMI1640 medium containing 10% human serum, as well as to medium containing 0.5% AlbuMAX alone. The infectivity of gametocytes produced with one supplement to Anopheles gambiae sensu stricto was assessed by standard membrane feeding assay and measuring both prevalence of infection and oocyst intensity. Results: Supplementation of medium containing 0.5% AlbuMAX with five supplements did not affect asexual growth of P. falciparum, and four of the five supplements supported early gametocyte production. The supplement producing the highest number of gametocytes, ITS-X, was further investigated and was found to support the production of mature gametocytes. Infection prevalence and oocyst intensity did not differ significantly between mosquitoes given a membrane feed containing gametocytes grown in medium with 0.5% AlbuMAX + ITS-X and those grown in medium with 10% human serum. Infection prevalence and oocyst intensity was significantly higher in case of ITS–X supplementation when compared to AlbuMAX alone. Infectious gametocytes were also produced from two field clones using ITS–X supplementation. Conclusions: Serum-free medium supplemented with ITS-X was able to support the growth of gametocytes of P. falciparum that were as infectious to An. gambiae as those grown in medium with 10% serum. This is the first fully serum-free culture system able to produce highly infectious gametocytes, thereby removing the requirement for access to serum for transmission assays. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is diagnosed relatively late and has a poor prognosis, requiring early detection to reduce the disease burden. This diagnostic test accuracy meta-analysis evaluated the serological diagnostic value of nine EBV-related IgA antibody panels (EBNA1-IgA, VCA-IgA, EA-IgA, Zta-IgA, EBNA1-IgA + VCA-IgA, VCA-IgA + EA-IgA, VCA-IgA + Rta-IgG, EBNA1-IgA + VCA-IgA + Zta-IgA and VCA-IgA + EA-IgA + Rta-IgG), aiming to identify suitable serological detection biomarkers for NPC screening. Methods: PubMed, Embase, China National Knowledge Infrastructure and Chinese BioMedical Literature Database were searched from January 1st, 2000 to September 30th, 2023, with keywords nasopharyngeal carcinoma, IgA, screening, early detection, early diagnosis, sensitivity and specificity. Articles on the diagnostic value of serum EBV-related IgA antibody panels for NPC were included. Study selection, data extraction, and quality assessment were performed independently by two researchers, and a third researcher was consulted in the case of disagreement. Bivariate models were used for statistical analysis. The quality of included studies was evaluated through Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). Results: A total of 70 articles were included, involving 11 863 NPC cases and 34 995 controls. Among the nine EBV-related IgA antibody panels, EBNA1-IgA + VCA-IgA [0.928 (0.898, 0.950)], VCA-IgA + Rta-IgG [0.925 (0.890, 0.949)], EBNA1-IgA + VCA-IgA + Zta-IgA [0.962 (0.909, 0.985)] and VCA-IgA + EA-IgA + Rta-IgG [0.945 (0.918, 0.964)] demonstrated higher pooled sensitivity (95%CI). In terms of diagnostic odds ratio (DOR) (95%CI), EBNA1-IgA + VCA-IgA [107.647 (61.173, 189.430)], VCA-IgA + Rta-IgG [105.988 (60.118, 186.857)] and EBNA1-IgA + VCA-IgA + Zta-IgA [344.450 (136.351, 870.153)] showed superior performance. Additionally, the SROC curves for EBNA1-IgA + VCA-IgA and VCA-IgA + Rta-IgG were more favorable. However, publication bias was detected for VCA-IgA (P = 0.005) and EBNA1-IgA + VCA-IgA (P = 0.042). Conclusions: In general, parallel detection of serum EBNA1-IgA, VCA-IgA and Zta-IgA antibodies using ELISA demonstrates better pooled sensitivity and DOR among the studied panels. In the cases where fewer indicators are used, serum VCA-IgA and EBNA1-IgA/Rta-IgG antibody panel exhibits a comparable performance. Trial registration: The International Prospective Register of Systematic Reviews registration number: CRD42023426984, registered on May 28, 2023. [ABSTRACT FROM AUTHOR]

Despite widespread cervical cancer (CC) screening programs, low participation has led to high morbidity and mortality rates, especially in developing countries. Because early-stage CC often has no symptoms, a non-invasive and convenient diagnostic method is needed to improve disease detection. In this study, we developed a new approach for differentiating both CC and cervical intraepithelial neoplasia (CIN)2/3, a precancerous lesion, from healthy individuals by exploring CC fatty acid metabolic reprogramming. Analysis of public datasets suggested that various fatty acid metabolizing enzymes were expressed at higher levels in CC tissues than in normal tissues. Correspondingly, 11 free fatty acids (FFAs) showed significantly different serum levels in CC patient samples compared with healthy donor samples. Nine of these 11 FFAs also displayed significant alterations in CIN2/3 patients. We then generated diagnostic models using combinations of these FFAs, with the optimal model including stearic and dihomo-γ-linolenic acids. Receiver operating characteristic curve analyses suggested that this diagnostic model could detect CC and CIN2/3 more accurately than using serum squamous cell carcinoma antigen level. In addition, the diagnostic model using FFAs was able to detect patients regardless of clinical stage or histological type. Overall, the serum FFA diagnostic model developed in this study could be a powerful new tool for the non-invasive early detection of CC and CIN2/3. [ABSTRACT FROM AUTHOR]

Background Cardiac injury caused by iron overload is the leading cause of mortality and morbidity in patients with beta-thalassemia, owing to frequent blood transfusion, increased iron overload, and blood hemolysis. Objective This research aimed to assess several novel cardiac biomarkers in the blood samples of children and adult patients with beta-thalassemia major (βTM), along with their respective control groups. These biomarkers included endothelin 1 (ET-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), atrial natriuretic peptide (ANP), growth differentiation factor-15 (GDF-15), and renalase (RNLS). Methods This case-control study was done on 46 patients with βTM (23 children <18 years, and 23 adults ≥18 years) from the Genetic Hematology Center in Thi-Qar province, Iraq, and 42 comparable controls in 2 groups (21 for each group) in the period from February to April 2023. Results Levels of ET-1, NT-proBNP, ANP, GDF-15, RNLS, and ferritin were higher in the children and adults with βTM than in the control subjects. Conclusion Elevations of the novel cardiac biomarkers ET-1, NT-proBNP, ANP, GDF-15, and RNLS in the sera of children and adult patients with βTM when compared with comparable control subjects confirm that the majority of patients with βTM are at risk of cardiac and cardiovascular complications even when there are no obvious symptoms, especially in children, which gives suitable predictive biomarkers. [ABSTRACT FROM AUTHOR]

Objectives Myositis-specific and associated autoantibodies are important biomarkers in routine clinical use. We assessed local testing performance for myositis autoantibodies by comparing line immunoassay (LIA) to protein radio-immunoprecipitation and identifying clinical characteristics associated with each myositis autoantibody in the MyoCite cohort. Methods Serum samples from patients within the MyoCite cohort, a well-characterized retro-prospective dataset of adult and juvenile idiopathic inflammatory myopathy (IIM) patients in Lucknow, India (2017–2020), underwent LIA at Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGIMS), Lucknow. Immunoprecipitation of 147 IIM patients' serum samples (125 adult-onset, 22 juvenile-onset) was conducted at the University of Bath, with researchers blind to LIA results. LIA performance was assessed against immunoprecipitation as the reference standard, measuring sensitivity, specificity and inter-rater agreement. Univariate and multivariate logistic regression determined clinical associations for specific myositis-specific autoantibodies. Results Immunoprecipitation identified myositis autoantibodies in 56.5% (n  = 83) of patient samples, with anti-Jo1 (n  = 16; 10.9%) as the most common, followed by anti-MDA5 (n  = 14, 9.5%). While LIA showed good agreement for anti-Jo1, anti-PL7 and anti-PL12 (Cohen's κ 0.79, 0.83 and 1, respectively), poor agreement was observed in other subgroups, notably anti-TIF1γ (Cohen's κ 0.21). Strongly positive samples, especially in myositis-specific autoantibodies, correlated more with immunoprecipitation results. Overall, 59 (40.1%) samples exhibited non-congruence on LIA and immunoprecipitation, and κ values for LIAs for anti-TIF1γ, anti-Ku, anti-PmScl, anti-Mi2 and anti-SAE ranged between 0.21 and 0.60. Conclusion While LIA reliably detected anti-Jo1, anti-PL7, anti-PL12, anti-MDA5 and anti-NXP-2, it also displayed false positives and negatives. Its effectiveness in detecting other autoantibodies, such as anti-TIF1γ, was poor. [ABSTRACT FROM AUTHOR]

Purpose: Short-term intake of the egg-protein hydrolysate Newtricious (NWT)-03 improved executive function, but underlying mechanisms and long-term effects, including other cognitive domains, are unknown. Methods: A 36-week randomized controlled trial involving 44 overweight/obese individuals experiencing elevated Subjective Cognitive Failures (SCF; aged 60–75 years) assessed the impact of daily consumption of 5.7 g of NWT-03 or placebo powders on cognitive performance (psychomotor speed, executive function, memory) and Cerebral Blood Flow (CBF), a marker of brain vascular function. Cognitive performance was evaluated using a neurophysiological test battery (CANTAB) and CBF was measured using magnetic resonance imaging perfusion method Arterial Spin Labeling (ASL). Serum samples were collected to determine brain-derived neurotrophic factor (BDNF) concentrations. Results: Anthropometrics, and energy and nutrient intakes remained stable throughout the trial. NWT-03 was well tolerated, and compliance was excellent (median: 99%; range: 87–103%). No overall intervention effects were observed on cognitive performance or CBF, but post-hoc analyses revealed significant improvements on executive function in women, but not men. Specifically, a reduction of 74 ms in reaction latency on the multitasking task (95% CI: −134 to −15; p = 0.02), a reduction of 9 between errors (95%CI: −14 to −3; p < 0.001), and a reduction of 9 total errors (95%CI: −15 to −3; p < 0.001) on the spatial working memory task were found in women. No intervention effects were observed on serum BDNF concentrations (p = 0.31). Conclusion: Long-term consumption of NWT-03 improved multitasking abilities and working memory in women with elevated SCF. Brain vascular function remained unaffected. Sex differences in executive function require additional clarification. [ABSTRACT FROM AUTHOR]

Interleukin-18 (IL-18) is a proinflammatory cytokine that primarily stimulates the Th1 immune response. IL-18 exhibits anticancer activity and has been evaluated in clinical trials as a potential cancer treatment. However, evidence suggests that it may also facilitate the development and progression of some cancers. So far, the impact of IL-18 on papillary thyroid cancer (PTC) has not been investigated. In this study, we found that the expression of IL-18 was significantly increased in PTC compared to normal thyroid tissue. Elevated IL-18 expression was closely associated with lymphovascular invasion and lymph node metastases. Furthermore, compared to PTC patients with no nodal metastasis, serum IL-18 levels were slightly increased in patients with 1–4 nodal metastases and significantly elevated in patients with 5 or more nodal metastases. The pro-metastatic effect of IL-18 may be attributed to the simultaneous increase in the expression of S100A10, a known factor that is linked to nodal metastasis in PTC. In addition, the activation of several pathways, such as the intestinal immune network for lgA production and Staphylococcus aureus infection, may be involved in the metastasis process. Taken together, IL-18 may trigger pro-metastatic activity in PTC. Therefore, suppressing the function of IL-18 rather than enhancing it appears to be a reasonable strategy for treating aggressive PTC. [ABSTRACT FROM AUTHOR]

Dysnatremia is common in donors and recipients of liver transplantation (LT). However, the influence of dysnatremia on LT prognosis remains controversial. This study aimed to investigate effects of donors' and recipients' serum sodium on LT prognosis. We retrospectively reviewed 248 recipients who underwent orthotopic LT at our center between January 2016 and December 2018. Donors and recipients perioperative and 3-year postoperative clinical data were included. Delta serum sodium was defined as the donors' serum sodium minus the paired recipients' serum sodium. Donors with serum sodium > 145 mmol/L had significantly higher preoperative blood urea nitrogen (BUN) (P < 0.01) and creatinine (Cr) (P < 0.01) than others. Preoperative total bilirubin (TBIL) (P < 0.01), direct bilirubin (DBIL) (P < 0.01), BUN (P < 0.01), Cr (P < 0.01) were significantly higher in the hyponatremia group of recipients than the other groups, but both of donors' and recipients' serum sodium had no effect on the LT prognosis. In the delta serum sodium < 0 mmol/L group, TBIL (P < 0.01) and DBIL (P < 0.01) were significantly higher in postoperative 1 week than the other groups, but delta serum sodium had no effect on the postoperative survival rates. Dysnatremia in donors and recipients of LT have no effect on postoperative survival rates, hepatic and renal function, but recipients with higher serum sodium than donors have significantly higher TBIL and DBIL at 1 week postoperatively. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication. Methods: Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data. Results: A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1 mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end. Conclusion: Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia. [ABSTRACT FROM AUTHOR]

Context Although the nutritional composition of organic food has been thoroughly researched, there is a dearth of published data relating to its impact on human health. Objective This systematic review aimed to examine the association between organic food intake and health effects, including changes in in vivo biomarkers, disease prevalence, and functional changes. Data Sources PubMed, EMBASE, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched from inception through Nov 13, 2022. Data Extraction Both observational and interventional studies conducted in human populations were included, and association between level of organic food intake and each outcome was quantified as "no association," "inconsistent," "beneficial correlation/harmful correlation," or "insufficient". For outcomes with sufficient data reported by at least 3 studies, meta-analyses were conducted, using random-effects models to calculate standardized mean differences. Data Analysis Based on the included 23 observational and 27 interventional studies, the association between levels of organic food intake and (i) pesticide exposure biomarker was assessed as "beneficial correlation," (ii) toxic metals and carotenoids in the plasma was assessed as "no association," (iii) fatty acids in human milk was assessed as "insufficient," (iv) phenolics was assessed as "beneficial", and serum parameters and antioxidant status was assessed as "inconsistent". For diseases and functional changes, there was an overall "beneficial" association with organic food intake, and there were similar findings for obesity and body mass index. However, evidence for association of organic food intake with other single diseases was assessed as "insufficient" due to the limited number and extent of studies. Conclusion Organic food intake was found to have a beneficial impact in terms of reducing pesticide exposure, and the general effect on disease and functional changes (body mass index, male sperm quality) was appreciable. More long-term studies are required, especially for single diseases. Systematic Review Registration PROSPERO registration no. CRD42022350175. [ABSTRACT FROM AUTHOR]

Autophagy is essential for oocyte maturation and preimplantation embryo development. ATG4C, a member of the ATG4 family, plays a crucial role in the autophagy process. The effect of ATG4C on the early embryonic development in pig has not been studied. In this study, the expression patterns of ATG4C were explored using qRT-PCR and immunofluorescence staining. Different concentrations of serum were added to in vitro maturation (IVM) medium to investigate its effects on oocyte maturation and embryonic development. Finally, the developmental potential of parthenogenetic embryos was detected by downregulating ATG4C in MII stage oocytes under 0 % serum condition. The results revealed that ATG4C was highly expressed in porcine oocytes matured in vitro and in parthenogenetic embryos. Compared with the 10 % serum group, the cumulus cell expansion, first polar body (PB1) extrusion rate, and subsequent developmental competence of embryos were reduced in the 0 % and 5 % serum groups. The mRNA levels of LC3 , ATG5 , BECLIN1 , TFAM , PGC1α , and PINK1 were significantly increased (P < 0.05) in the 0 % serum group. ATG4C was significantly upregulated in the embryos at the 1-cell, 2-cell, 8-cell, and 16-cell stages in the 0 % serum group (P < 0.05). Compared with the negative control group, downregulation of ATG4C significantly decreased the 4-cell, 8-cell, and blastocyst rates (P < 0.05), and the expression of genes related to autophagy, mitochondria, and zygotic genome activation (ZGA) was significantly decreased (P < 0.05). The relative fluorescence intensity of LC3 and mitochondrial content in the ATG4C siRNA group was significantly reduced (P < 0.05). Collectively, the results indicate that ATG4C is highly expressed in porcine oocytes matured in vitro and in early embryos, and inhibition of ATG4C effects embryonic developmental competence by decreasing autophagy, mitochondrial content, and ZGA under serum-free condition. • ATG4C was broadly expressed in porcine oocyte matured in vitro and during early embryonic development. • ATG4C expression was significantly increased in porcine embryos under serum-free conditions. • ATG4C downregulation decreased embryonic developmental potential by influencing autophagy, mitochondrial activity, and zygotic genome activation (ZGA). [ABSTRACT FROM AUTHOR]

Objective: The study aimed to assess Sirt6 levels in serum of knee osteoarthritis (OA) patients compared to healthy individuals to evaluate its correlation with OA and to understand how Sirt6 is linked with the change in IL-6 levels. Methods: The cross-sectional study involved 50 knee OA patients clinically diagnosed as per the American College of Rheumatology guidelines and 50 healthy controls. Radiological examination as per Kellgren–Lawrence (KL) criteria was done to determine the disease severity. Peripheral blood samples were collected from each participant, and serum Sirt6 and IL-6 levels were measured using ELISA. Results: The serum Sirt6 levels in knee OA patients were significantly lower as compared to healthy controls (p = 0.023). Patients with knee OA of KL grade 4 had significantly lower Sirt6 levels as compared to those with KL grade 2 OA (p = 0.031). Individuals of younger age group had higher Sirt6 levels compared to older age group. IL-6 levels in knee OA patients were significantly higher as compared to controls (p = 0.007). A negative correlation was observed between serum Sirt6 and IL-6 levels (r = − 0.407; p = 0.035). Conclusion: The study concludes that serum Sirt6 levels are inversely associated with knee OA and may serve as a potential biomarker for the disease. Moreover, a negative correlation between Sirt6 and IL-6 levels was observed in this study. Further investigations are necessary to confirm these findings and to explore the mechanisms by which Sirt6 and IL-6 are involved in OA. [ABSTRACT FROM AUTHOR]

Background: Vitamin B12 deficiency is widely prevalent in all age groups which is of major concern. However, there is no valid Food Frequency Questionnaire (FFQ) for dietary vitamin B12 estimation. Hence, we aimed to develop and validate an FFQ for the estimation of dietary intake of Vitamin B12. Materials and Methods: Commonly consumed B12-rich food items were selected from literature and filtered using a market survey. For concordant and discriminant validation, B12 and homocysteine levels were estimated. To establish convergent validity, the Cobalamin Intake in North Indians by Food Frequency Questionnaire (COIN-FFQ) and 72-hour dietary recall (72HrDR) were both administered to the same subjects. The COIN-FFQ was readministered after initial administration for test-retest reliability. Internal consistency of the FFQ was then tested using Cronbach's alpha. Results: We enrolled 115 adults with a mean age and weight of 31.9 ± 8.7 years and 66.0 ± 11.8 kg, respectively. In total, 19.1% were vegetarian. The dietary B12 using COIN-FFQ (n = 60; mean = 4.3 ± 1.8 µg/d) was significantly correlated (r = 0.255; P = 0.049) with serum levels (mean = 120.1 ± 62.6 pmol/L) establishing concordant validity. A significant difference was noted between the dietary, serum B12, and homocysteine levels of vegetarians versus nonvegetarians establishing discriminant validity (mean diff 1.4 (0.5-2.4), P = 0.004; Z-statistic -2.182, P value 0.029, and Z-statistic -2.438; P value 0.015), respectively. FFQ was strongly correlated with 72HrDR and test--retest FFQ (n = 27; r = 0.814, P < 0.001 and r = 0.869, P < 0.001, respectively) establishing convergent validity and test--retest reliability. The internal consistency with Cronbach's alpha was in the acceptable range, 0.631 (n = 115). Conclusion: The newly developed COIN-FFQ is valid and reliable in estimating dietary B12 intake. [ABSTRACT FROM AUTHOR]

Summary: Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions. Purpose: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs). Methods: A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses. Results: Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 − 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias. Conclusions: Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs. Trial registration: PROSPERO registration number: CRD42023427508. [ABSTRACT FROM AUTHOR]

It is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. In individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N -acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. Our findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC. • Serum levels of Cu and CER decreased in men with MDD, while the Cu/Zn ratio increased in women with MDD. • In males with MDD, a gender-specific decrease in the NAA/PCr + Cr ratio was noted in the left ACC. • The Cu/Zn ratio and Fe levels in male MDD patients are associated with changes in neurometabolism in the ACC. [ABSTRACT FROM AUTHOR]

Objective: Limited studies have been conducted on insulin index/load, with inconsistent results regarding the glycemic index/load in relation to cardiometabolic risk factors among people with diabetes. The present study aimed to reveal the association of dietary glycemic index and load and dietary insulin index and load with cardiometabolic risk factors among people with diabetes. Method: This cross-sectional study was performed on 88 adults with diabetes who enrolled in the Cohort Study of Employees of Shiraz University of Medical Sciences. The scores of dietary glycemic index (DGI), dietary glycemic load (DGL), dietary insulin index (DII), and dietary insulin load (DIL) were measured using a 116-item food frequency questionnaire (FFQ). Multivariate linear regressions were used to associate each dietary score with fasting blood glucose (FBG), triglyceride, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and systolic and diastolic blood pressure. Results: DGI was significantly associated with serum FBG (β; 0.24, 95% CI; 0.02, 0.46) and triglyceride (β; 0.53, 95% CI; 0.002, 1.06) levels but not TC, HDL, LDL, or blood pressure after adjusting for age, sex, education, marital status, smoking, body mass index, energy intake, physical activity, having other diseases, and family history of diabetes. Neither DGL, DII, nor DIL was significantly associated with each of the cardiometabolic risk factors after controlling for the confounders. Conclusion: A diet with a higher glycemic index accompanied by a higher serum FBG and triglyceride level. Further studies are needed to determine the association of DGL, DII, and DIL with cardiometabolic risk factors. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of high‐intensity interval training (HIIT) on periodontitis (PD) progression and behavioural outcomes. Materials and Methods: Forty‐eight Wistar rats were divided into four groups: non‐trained (NT); non‐trained with PD; HIIT with PD; and HIIT. The HIIT protocol, involving daily treadmill sessions, spanned 8 weeks, with PD induced by ligature after the 6th week. Behavioural tests were conducted to assess anxiety and memory. Post euthanasia, we evaluated the systemic inflammatory profile and oxidative stress markers in the hippocampus and amygdala. A morphological evaluation and elemental composition analysis of the mandibular alveolar bone were performed. Results: PD exacerbated alveolar bone level, bone surface damage and alterations in calcium and phosphorus percentages on the bone surface (p <.05), while HIIT attenuated these changes (p <.05). HIIT improved systemic inflammatory markers altered by PD (tumour necrosis factor [TNF]‐α, interleukin [IL]‐10, TNF‐α/IL‐10 and IL‐1β/IL‐10 ratios, p <.05). PD animals exhibited lower total antioxidant capacity and levels of thiobarbituric acid reactive substances in the amygdala and hippocampus, respectively (p <.05). HIIT maintained these parameters at levels similar to those in NT animals. HIIT improved anxiety and memory outcomes altered by PD (p <.05). Conclusions: HIIT attenuates systemic inflammation, anxiety and memory outcomes promoted by PD. [ABSTRACT FROM AUTHOR]

Background/Aim: The molecular classification of breast cancer has enabled targeted therapy for specific molecular subtypes. Nestin, which has been studied for its role in oncogenesis, could contribute to this direction. This study aimed to investigate the differences between serum nestin levels and molecular profiling, as well as histopathological tumor types, in women who underwent surgery for breast cancer. Patients and Methods: Women who underwent surgery for breast cancer at the Breast Unit of the 1st Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens were prospectively included. Patients’ demographic data were recorded and serum nestin levels were measured. Molecular biomarker analysis was performed, as well as histopathologic assessment. Results: Seventy patients were included in the analysis. Among patients with breast cancer, 93% were estrogen receptor (ER) positive, 91% were progesterone receptor (PR) positive, and 43% were human epidermal growth factor receptor 2 (HER2) positive. Ki67 was expressed in 16% of patients and p53 was expressed in 32% of patients. Invasive ductal carcinoma was diagnosed in 80% of patients, with 44% of tumors classified as T1 and 46% as T2. Additionally, 43% were G1 and 56% were N0, while 34% were N1. No statistically significant difference was observed between serum nestin levels and ER, PR, HER2, Ki67, and p53 expression. Furthermore, no difference was observed between serum nestin levels and breast cancer histological type, size, N-stage, and grading. Conclusion: The diagnostic and prognostic role of circulating nestin for breast cancer was not confirmed and no correlation with immunohistochemistry results was observed. Thus, the necessity of larger prospective studies is enhanced. [ABSTRACT FROM AUTHOR]

Biosensing for diagnostics has risen rapidly in popularity over the past decades. With the discovery of new nanomaterials and morphologies, sensitivity is being constantly improved enough for reliable detection of trace biomarkers in human samples, like serum or sweat. This precision has enabled detailed research on the efficacy of biosensors. However, current biosensors suffer from reduced speed of operation. To make better use of this sensitivity, the development of a conductometric biosensor with in-situ use of an Laser Emitting Device (LED) display can provide rapid determination of sample results, steadily pushing biosensors toward more clinical, point-of-care (POC) applications. In this research, a simple LED was used for facile optical determination and visual output of an ultrasensitive bio-signal amplification circuit was made to interface with a B-type Natriuretic Peptide (BNP) biosensor. Tuning circuit gain enables an elegant method for adjustable separation of concentrations into 3 discrete categories: sub-threshold, analog, and saturation regions. These regions corresponded to 0 < [C] < 500 pg/mL (25, 100, 250 pg/mL, LED off), 500 < [C] < 1000 pg/mL (LED varying intensity), and 1000 pg/mL < [C] (LED full intensity). System efficacy was tested using human blood serum samples from University of Pittsburgh Medical Center patients, which were able to be accurately detected and sorted for rapid low cost and power. determination without need for complex digital elements. Additional specificity testing suggests insignificant impact of non-target biomarkers. [ABSTRACT FROM AUTHOR]

Copyright of Equine Veterinary Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Peripheral neuropathy is a prevalent complication in plasma cell disorders, posing significant diagnostic and therapeutic challenges. This study presents three cases initially diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Despite initial symptom regression post-immunomodulatory treatment, the patients exhibited progressive neurological deficits. Advanced laboratory evaluation confirmed monoclonal protein presence, yet traditional diagnostic methods, including bone marrow biopsy and flow cytometry, yielded normal results. Utilizing 18F-FDG PET/CT, we identified multiple hypermetabolic vertebral lesions, which upon biopsy, confirmed the diagnosis of plasmacytoma. Our findings underscore the utility of PET/CT as a reliable diagnostic tool for monoclonal gammopathy associated neuropathy, advocating for its consideration in cases with equivocal diagnosis. When the diagnosis is in doubt, biopsy of a lesion may facilitate early and accurate diagnosis, potentially influencing treatment strategies and patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The presence of a polymicrobial dysbiotic film in direct and constant contact with periodontal tissues initiates the host immune response. Interleukin 18 (IL-18) triggers up-regulates the production of other proinflammatory cytokines (TNF-α, IL-1β, IL-6), creating a vicious cycle that expands the inflammatory and destructive process in the periodontal tissue. A systematic review and meta-analysis was carried out with the main propose to investigate IL-18 expression in different biological samples from subjects with chronic periodontitis. Methods: The protocol followed PRISMA guidelines and was registered in Open Science Framework (OSF):https://doi.org/10.17605/OSF.IO/BS9GM. A digital search was conducted in the databases PubMed, ScienceDirect, Google Scholar, Web of Science and Dentistry & Oral Sciences Source databases were consulted from March 15th, 2005 to February 10th, 2023. Study quality was assessed using the JBI tool for cross-sectional studies and clinical trials. A meta-analysis was performed using a random/fixed effects model to evaluate the concentration of IL-18 in serum, plasma, saliva, gingival tissue and GCF of exposure group compared to control group. Results: The search strategy provided a total of 3,156 articles, of which 18 investigations met the inclusion criteria and 15 articles were quantitatively analyzed. The total number of patients studied was 1,275 (682 cases and 593 controls). The meta-analysis revealed significantly elevated IL-18 levels of serum, saliva and GCF of subjects with chronic periodontitis compared to healthy subjects (Serum: SMD = 62.73, 95%CI: 25.43-100.03, Z = 3.29, p = 0.001*; Saliva: SMD = 243.63, 95%CI: 8.68-478.59, Z = 2.03, p = 0.042*; GCF: SMD = 150.26, 95%CI: 56.86-243.66, Z = 3.15, p = 0.02*). Conclusion: IL-18 levels in serum, saliva and GCF could have the potential to be used as complementary diagnostic tools to the clinical and radiographic parameters in subjects with periodontitis. [ABSTRACT FROM AUTHOR]

Background: Proteomics and metabolomics offer substantial potential for advancing kidney transplant research by providing versatile opportunities for gaining insights into the biomolecular processes occurring in donors, recipients, and grafts. To achieve this, adequate quality and numbers of biological samples are required. Whilst access to donor samples is facilitated by initiatives such as the QUOD biobank, an adequately powered biobank allowing exploration of recipient-related aspects in long-term transplant outcomes is missing. Rich, yet unverified resources of recipient material are the serum repositories present in the immunological laboratories of kidney transplant centers that prospectively collect recipient sera for immunological monitoring. However, it is yet unsure whether these samples are also suitable for -omics applications, since such clinical samples are collected and stored by individual centers using non-uniform protocols and undergo an undocumented number of freeze–thaw cycles. Whilst these handling and storage aspects may affect individual proteins and metabolites, it was reasoned that incidental handling/storage artifacts will have a limited effect on a theoretical network (pathway) analysis. To test the potential of such long-term stored clinical serum samples for pathway profiling, we submitted these samples to discovery proteomics and metabolomics. Methods: A mass spectrometry-based shotgun discovery approach was used to obtain an overview of proteins and metabolites in clinical serum samples from the immunological laboratories of the Dutch PROCARE consortium. Parallel analyses were performed with material from the strictly protocolized QUOD biobank. Results: Following metabolomics, more than 800 compounds could be identified in both sample groups, of which 163 endogenous metabolites were found in samples from both biorepositories. Proteomics yielded more than 600 proteins in both groups. Despite the higher prevalence of fragments in the clinical, non-uniformly collected samples compared to the biobanked ones (42.5% vs 26.5% of their proteomes, respectively), these fragments could still be connected to their parent proteins. Next, the proteomic and metabolomic profiles were successfully mapped onto theoretical pathways through integrated pathway analysis, which showed significant enrichment of 79 pathways. Conclusions: This feasibility study demonstrated that long-term stored serum samples from clinical biorepositories can be used for qualitative proteomic and metabolomic pathway analysis, a notion with far-reaching implications for all biomedical, long-term outcome-dependent research questions and studies focusing on rare events. [ABSTRACT FROM AUTHOR]

AbstractHead injury is a potentially lethal and frequently occurring condition in the emergency department (ED). Reliable and fast diagnosis is important both for patients and flow in the ED. Circulating S100B is used to rule out the need for head computer tomography in low-risk patients with mild head injury. The flow of these patients through the ED would benefit from shorter turn-around time. Standard serum clotting tubes require 30-60 min clotting time, followed by an analysis time of 45 min. Here, we evaluated the performance of two alternative blood collection tubes; a rapid serum tube (RST) with a recommend clotting time of 5 min and a hirudin tube (HIR) for instant anticoagulation. S100B measurement was performed on paired blood samples from 221 subjects using a Roche Cobas 602 analyser. The performances of the alternative tubes were evaluated by method comparison to the standard serum clotting tube, repeatability and agreement of results obtained from alternative tubes compared with the standard clotting tube. Both alternative tubes had a minor positive bias (RST = 0.011 µg/L, HIR = 0.008 µg/L). The repeatability was 2% for RST and 10% for HIR, while being 4% for the standard clotting tube. In the agreement analysis, the positive and negative predictive values for RST were 62% and 100% while being 73% and 99% for HIR respectively. Our study suggests that RST is a feasible alternative to reduce laboratory turn-around time in S100b analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: There are no reliable prognostic biomarkers for ovarian cancer. The immune tumor suppressive marker interleukin-10 has been shown to be elevated in cancer, specifically in ovarian cancer. This study aims to correlate interleukin-10 levels in the ascites and sera of ovarian cancer patients to correlate with cancer-related data and outcomes. Our findings suggest a prognostic role for interleukin-10 that may be related to its immunosuppressive function in the tumor microenvironment. Future studies are needed to validate these results. This study highlights a potential target for novel therapeutic approaches. Interleukin-10 (IL-10) has been shown to be present at high levels in the ascites of ovarian cancer (OC) patients; however, little is known about its prognostic value. We sought to correlate IL-10 levels in ascites and sera of OC patients with clinicopathologic characteristics and oncologic outcomes. IL-10 levels and clinical data from biobanked ascites and serum samples of OC patients were evaluated. Receiver operating characteristic curves were used to quantify marker performance and identify IL-10-high and IL-10-low groups. Correlations between IL-10 levels and clinicopathologic data were performed. Survival outcomes were calculated, while the factors affecting them were also investigated. A total of 106 patients had ascites samples, of which 44 serum samples were also available. Mean ascites IL-10 levels were significantly higher in patients with serous histology compared to endometrioid histology (p = 0.024). Fold-change in ascites IL-10 during treatment positively correlated with clinical response, as determined by a change in serum cancer antigen (CA)-125 levels (p = 0.0126). Median progression-free survival (PFS) and overall survival (OS) were shorter in patients with high compared with low ascites IL-10 levels (PFS: 18 versus 60 months; p = 0.007, OS: 42 versus 85 months; p = 0.029). A significant positive correlation was seen between ascites and sera IL-10 levels (p = 0.019). In multivariable analyses, a high ascites IL-10 level was associated with a significantly worse prognosis (PFS hazard ratio (HR) = 1.93; p = 0.02). Patients with high ascites levels of IL-10 have worse outcomes, which are likely reflective of the immunosuppressive effect of IL-10. This highlights its potential role as an immunomodulator in the tumor microenvironment, leading to OC immune evasion. [ABSTRACT FROM AUTHOR]

Simple Summary: Heretofore, a series of research has targeted enhancing feed efficiency and identifying dependable feed efficiency biomarkers, yet less research has focused on improving RFI in Chuanzang black pigs. Therefore, our study facilitates a deeper understanding of the differences in serum and urine metabolites of Chuanzang black pigs with different residual feed intakes in seeking to identify differential metabolites with residual feed intake. Our study used a nontargeted metabolomics approach to analyze pig metabolite markers by differences in Chuanzang black pigs' serum and urine metabolites, providing new insights into the biological differences in residual feed intake selection in Chuanzang black pigs. We believe this paper would be of great interest to breeders of animals. This study was conducted to evaluate associations of blood variables and urine variables with different residual feed intakes (RFIs) in growing Chuanzang black (CB) pigs. A total of 228 growing CB boars from 99 days were used. The same basal diet was offered ad libitum and individual feed intake and body weight were measured over a period of 181 d. The CB pigs were categorized based on their residual feed intake values, with six individuals each from the high and low ends selected and divided into two groups: the low residual feed intake group (LS) and the high residual feed intake group (HS). Serum and urine samples were collected at the end of the experiment for determination of metabolomics profiling. Results showed that there were significantly different metabolites in serum and urine of different RFI groups (fold-change, FC > 2.0 or FC < 0.5, and p < 0.05), and 21 metabolites were identified in serum and 61 in urine. Cluster analysis showed that 20 metabolites were up-regulated and one metabolite was down-regulated in serum; 44 metabolites were up-regulated and 17 metabolites were down-regulated in urine. Kyoto Encyclopedia of Genes and Genomes analysis showed that the differential metabolites of serum were enriched in linoleic acid metabolism, and the differential metabolites of urine were enriched in steroid hormone biosynthesis, taurine and hypotaurine metabolism, and primary bile acid biosynthesis. The correlations between serum metabolites and urine metabolites indicated a significant positive correlation between all fatty acyls in serum metabolites and L-glutamate in urine. However, no compelling genetic or blood biomarkers have been found to explain the differences in RFI, suggesting multiple approaches to effective feed use in pigs. This study provides new insights into the subsequent assessment of RFI by metabolomics profiling, as well as the development of novel feed additives for the factors that will facilitate future research directions in CB pigs. [ABSTRACT FROM AUTHOR]

While COVID-19's urgency has diminished since its emergence in late 2019, it remains a significant public health challenge. Recent research reveals that the molecular intricacies of this virus are far more complex than initially understood, with numerous post-translational modifications leading to diverse proteoforms and viral particle heterogeneity. Mass spectrometry-based proteomics of patient serum/plasma emerges as a promising complementary approach to traditional diagnostic methods, offering insights into SARS-CoV-2 protein dynamics and enhancing understanding of the disease and its long-term consequences. This article highlights key findings from three years of pandemic-era proteomics research. It delves into biomarker discovery, diagnostic advancements, and drug development efforts aimed at monitoring COVID-19 onset and progression and exploring treatment options. Additionally, it examines global protein abundance and post-translational modification profiling to elucidate signaling pathway alterations and protein-protein interactions during infection. Finally, it explores the potential of emerging multi-omics analytic strategies in combatting SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Objective To explore the effects of vascular endothelial growth factor (VEGF), insulin-like growth factor 1(IGF-1) and neuromodulatory protein 1(NRG1) on first-episode schizophrenia patients. Meth- ods A total of 71 patients with first-episode schizophrenia admitted to the hospital from September 2021 to January 2023 were retrospectively selected as the study group, and 71 healthy volunteers who underwent phys- ical examination during the same period were selected as the control group. At the same time, according to the results ofpositive and negative symptom scale (PANSS) score results, the study group was divided into the high score subgroup(70 points, 33 cases) and the low score subgroup (<70 points, 38 cases). The study group was divided into cognitive dysfunction group (29 cases) and normal cognitive function group (42 cases) according to the results of MATRICS recognized cognitive battery(MCCB). The levels of serum VEGF, IGF1, and NRG1 in each group were compared, and their correlation with MCCB and PANSS scores was analyzed. Results The levels of serum VEGF, IGF1, and NRG1 in the study group were lower than those in the control group, and the differences were statistically significant (P<0.05). The levels of serum VEGF, IGF1, and NRG1 in the cognitive dysfunction subgroup were lower than those in the normal cognitive function sub- group, and the differences were statistically significant (P<0.05). The levels of serum VEGF, IGF1, and NRG1 in the low score subgroup were higher than those in the high score subgroup, and the differences were statistically significant (P<0.05). The levels of serum VEGF, IGF1, and NRG1 were positively correlated with MCCB and PANSS scores (P<0.05). Conclusion The levels of serum VEGF, IGF1 and NRG1 in pa- tients with schizophrenia are lower than those in healthy people, which are closely related to mental symptoms and cognitive function. [ABSTRACT FROM AUTHOR]

Objective To investigate the influence of serum vitamin D levels on individuals infected with human immunodeficiency virus type 1(HIV-1). Methods A total of 411 treated HIV-1 infected patients undergoing HIV-1 DNA testing at the First Hospital of Changsha from January 2021 to July 2023 were included. Among them. 92 infected individuals with vitamin D deficiency were subjected to supplementary test and divided into study group (42 cases) and control group (50 cases) according to voluntary basis. Analysis included assessment of vitamin D deficiency across different demographic and clinical characteristics of HIV-1 infected individuals, comparison of serum vitamin D levels, T-cell subset levels, and HIV-1 DNA levels between the two groups, and correlation analysis of serum vitamin D levels with T-cell subsets and HIV-1 DNA levels. Results Significant differences in serum vitamin D deficiency rates were observed among HIV-1 infected individuals across different age groups, antiretroviral therapy (ART) durations, CD8+T-cell counts, and CD4/CD8 ratios(P<0.05). Individuals aged 40 years exhibited significantly lower rates of vitamin D deficiency compared to those aged 40 years(P<0.05). Serum vitamin D levels were negatively correlated with CD8+T-cell counts(r=-0.2510,P<0.05), positively correlated with CD4/CD8 ratios (r=0.1726,P<0.05), and showed no significant correlation with CD4+T-cell counts(P>0.05). Serum vitamin D levels were negatively correlated with HIV-1 DNA levels (r=-0.1022,P<0.05) and positively correlated with ART duration(r=0.1274,P<0.05). There were no statistically significant differences in baseline serum vitamin D levels and T-cell subset levels between the study and control groups (P>0.05). At the 48-week follow-up, the study group showed significantly higher levels of serum vitamin D, CD4+T-cell counts, and CD8 T-cell counts compared to baseline(P<0.05),whereas the control group exhibited only higher serum vitamin D levels compared to baseline (P=0.007). Comparison of CD4+T-cell counts, CD8+T-cell counts, and CD4/CD8 ratios between the two groups at 48 weeks did not show statistically significant differences (P>0.05). At the 48-week follow-up, the study group had significantly higher serum vitamin D and CD8+T-cell counts compared to the control group (P<0.05). Conclusion Younger individuals and those in early stages of ART with HIV-1 infection tend to have relatively lower serum vitamin D levels. Supplementation with vitamin D3 may improve immune function and reduce viral reservoir levels. [ABSTRACT FROM AUTHOR]

Introduction: Alagille syndrome (ALGS) is a rare, genetic, multisystem disorder commonly associated with cholestatic liver disease; patients with ALGS may experience elevated serum bile acids and severe pruritus with associated impaired sleep. The ileal bile acid transporter (IBAT) is located on the luminal surface of enterocytes in the terminal ileum; this transport protein mediates resorption of conjugated bile acids for recirculation back to the liver. Inhibition of IBAT disrupts the enterohepatic circulation and leads to fecal elimination of bile acids. Areas covered: Here, the role of odevixibat as a novel, nonsurgical approach to interrupting the enterohepatic circulation from the intestine by inhibition of IBAT is reviewed, specifically in reference to currently available data on pharmacologic IBAT inhibition. IBAT inhibition has been shown to reduce serum bile acids and pruritus in trials of cholestatic liver diseases in children including ALGS. Expert opinion: Odevixibat or IBAT inhibitor should be considered as a first-line treatment for ALGS to improve pruritis, quality of life and liver-related outcomes including absence of liver transplant, surgical biliary diversion, hepatic decompensation, and death. [ABSTRACT FROM AUTHOR]

Simple Summary: Signals generated from passing infrared radiation through biological samples such as serum can create distinct wave patterns, or "fingerprints", that can be used to distinguish samples with or without diseases such as osteoarthritis. In research, the collection of a large database of samples for studying diseases such as osteoarthritis can take years and requires the storage of samples in freezers. The aging of samples in the frozen state can change both the quality of samples and the results that are obtained from aged samples versus fresh, frozen samples. In this study, serum and joint fluid from dogs that had knee osteoarthritis and those that did not were used to compare the quality of the generated fingerprints from samples after short- and long-term storage in the frozen state. The results showed that even though aging of samples in the frozen state causes statistically significant differences between the fingerprint of samples, these changes only account for 2–3% of the overall variance in the spectroscopic data set (compared, e.g., to the variability stemming from differences between samples having been withdrawn from arthritic versus healthy dogs, which amounts to 77% for serum or even 86% for synovial fluid). The fingerprint of both serum and joint fluid samples after long-term storage of about seven years could still be used to distinguish between arthritic and healthy dogs with a high degree of accuracy. Mid-infrared spectral (MIR) patterns of serum and synovial fluid (SF) are candidate biomarkers of osteoarthritis (OA). The impact of long-term storage on MIR spectral patterns was previously unknown. MIR spectra of canine serum (52 knee-OA, 49 control) and SF (51 knee-OA, 51 control) were obtained after short-term and long-term storage in −80 °C. Multilevel simultaneous component analysis and partial least squares discriminant analysis were used to evaluate the effect of time and compare the performance of predictive models for discriminating OA from controls. The median interval of storage between sample measurements was 5.7 years. Spectra obtained at two time points were significantly different (p < 0.0001); however, sample aging accounted for only 1.61% and 2.98% of the serum and SF profiles' variability, respectively. Predictive models for discriminating serum of OA from controls for short-term storage showed 87.3 ± 3.7% sensitivity, 88.9 ± 2.4% specificity, and 88.1 ± 2.3% accuracy, while for long-term storage, they were 92.5 ± 2.6%, 97.1 ± 1.7%, and 94.8 ± 1.4%, respectively. Predictive models of short-term stored SF spectra had 97.3 ± 1.6% sensitivity, 89.4 ± 2.6% specificity, and 93.4 ± 1.6% accuracy, while for long-term storage they were 95.7 ± 2.1%, 95.7 ± 0.8%, and 95.8 ± 1.1%, respectively. Long-term storage of serum and SF resulted in significant differences in MIR spectral variables without significantly altering the performance of predictive algorithms for discriminating OA from controls. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors are a heterogeneous group of tumors located mainly in the gastrointestinal tract or the respiratory system. We aimed to determine the concentrations of IGF-1R, ERK2, and EGFR using the ELISA method in serum samples from patients with NETs and from a control group. Results were evaluated with the selected demographic, clinicopathological, and biochemical characteristics. The analyses performed on a group of patients (80 in the study group and 62 in the control group) showed that the concentration of EGFR in patients with neuroendocrine tumors was significantly higher (p < 0.001) compared to the control group. Additionally, a significantly higher (p < 0.001) EGFR concentration was found in GEP-NET. Our results indicate that impaired EGFR signaling pathways are important in the context of neuroendocrine tumors. The data presented are a good starting point for further analysis of these proteins. [ABSTRACT FROM AUTHOR]

Cells exposed to stressors of various origin activate protective mechanisms that include the expression of heat shock proteins (Hsps)/molecular chaperones belonging to several families. Well-characterized inducible Hsp70 is present in all human cell-types and biological fluids, including blood, urine, and saliva. The presence of anti-Hsp70 autoantibodies in the serum of healthy individuals has already been confirmed, and their elevated titers positively correlated with the severity of several pathological conditions, including coeliac disease and dermatitis herpetiformis - a cutaneous manifestation of coeliac disease. Here, using an indirect enzyme-linked immunosorbent assay, we demonstrate, for the first time, that anti-Hsp70 autoantibodies are present in the saliva and urine of healthy individuals. Although the occurrence of anti-Hsp70 autoantibodies in the biological fluids of healthy individuals is intriguing, their physiological role is currently unknown. It is believed that antibodies reacting with self-molecules present in the serum of healthy individuals are part of natural autoantibody pool with multiple regulatory functions. On the other hand, some autoantibodies (e.g., typical of autoimmune bullous skin diseases or systemic lupus erythematosus) may be present before the onset of the disease and serve as specific predictive biomarkers. Therefore, we would like to initiate a discussion or future research direction on the use of anti-Hsp70 autoantibodies as a potential "biomarker" in the diagnosis or prediction of autoimmune diseases. Our findings can be considered in biomedical research to develop noninvasive, inexpensive and easy-to-use tests. Nevertheless, large-scale comparative studies should be initiated, involving the collection and analysis of biological samples such as saliva or urine from patients suffering from autoimmune diseases or other inflammatory or neoplastic diseases, to determine whether the levels of anti-Hsp70 autoantibodies are indeed elevated and whether they correlate with the clinical picture of any disease or established biomarkers. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to investigate serum chitotriosidase level in tuberculosis patients, its relationship with microbiological and clinical parameters, and response to treatment. Materials and methods: This longitudinal panel study included 149 patients with confirmed TB disease. Serum chitotriosidase activity was measured at the beginning and the end of treatment. Factors associated with chitotriosidase activity were explored using univariate and multivariable logistic regression analysis. Results: Out of 149 study participants, 71(47.7%) were female. The mean age was 53.0 (SD = 18.2). Majority of cases were new 118(79.2), predominantly 145 (97.3%) having pulmonary tuberculosis. More than half of the patients were sputum smear positive 91 (61.1%) while culture positive in 146 (98%) of them. According to radiological findings, cavitary lesions were found in 92 (63.4%) patients. Anti TB treatment was associated with significant decrease in serum chitotriosidase level (< 0.001). New TB treatment (OR = 4.41%;95% CI = 1.20–9.89), and cavitary lesions (OR = 3.86;95%CI = 0,59-26.57) were found to be significantly associated with decrease of chitotriosidase activity. Conclusions: The results of our study showed that serum chitotriosidase values are strong biomarkers for starting anti TB treatment and for treatment monitoring, since decrease in serum chitotriosidase level can predict favorable treatment response in patients with tuberculosis. Further studies are needed to explore these, and other factors associated with chitotriosidase activity among tuberculosis patients. [ABSTRACT FROM AUTHOR]

Understanding the variations in activity of enzymes involved in the immune response of insects is important for developing effective microbial insecticides against pest species, the determination of bacteria dosage that caused variation of enzyme activities would assist us to prepare effective concentrations of microbial insecticides. In this study, we measured the activities of acid phosphatase (ACP), phenoloxidase (PO), peroxidase (POD), glutathione peroxidase (GSH-px), glutathione reductase (GR), and glutathione S-transferase (GST) in haemocytes and serum of larvae of the pest Heterolocha jinyinhuaphaga Chu (Lepidoptera: Geometridae) infected with Escherichia coli at different time points post-infection. Infection of fifth-instar larvae with different dosages of E. coli led to significant increases in the activities of these enzymes in haemocytes and serum at 3, 6, 12, and 24 h post-infection. Enzyme activities in haemocytes peaked at 6 h post-infection, but their activities began to decrease at 12 h post-infection. Enzyme activities in serum peaked at 12 h post-infection, and they began to decrease at 24 h post-infection. Additionally, enzyme activities increased with increasing dosages of E. coli. The activities of ACP, PO, POD, and GSH-px peaked at 1 × 107 indiv/mL, and the activities of GR and GST peaked at 1 × 106 indiv/mL, activities decreased thereafter. Two - way analysis of variance showed that the interaction of infection time and dosages of E. coli had no significant effect on the enzyme activities in haemocytes and serum of H. jinyinhuaphaga larvae (P > 0.05). [ABSTRACT FROM AUTHOR]

This research introduces a novel electrochemical sensor designed for the detection of chloroquine. The sensor was developed via a simple method to synthesize TiO2 nanoparticles on reduced graphene oxide. The modified electrodes created in this manner exhibited high electrocatalytic activity and distinct chemical reactivity. Various techniques were utilized to perform morphological characterization of the nanocomposites. These techniques revealed alterations revealed changes in functional groups and the attachment of titanium to the reduced graphene oxide present on the electrode surface, thereby elucidating the reasons for the enhanced electrochemical performance. The sensor had a broad measurement range for chloroquine, capable of detecting concentrations as low as 10−8 M. It is applicable for diverse sample analyses, including water, pharmaceuticals, human urine, and serum, with satisfaction ranging between 97 and 99%. The development strategy. An electrochemical sensor was developed using titanium oxide nanoparticles attached to reduced graphene oxide TiO2-NPs @RGO/GCE for real-time detection of chloroquine in real contaminated samples such as human urine, human serum, and tap water with low detection limit. [ABSTRACT FROM AUTHOR]

Background: Little is known about reintubations outside of the operating room. The objective of this study was to evaluate the reintubation rate and mortality after emergent airway management outside operating room (OR), including intensive care unit (ICU) and nonICU settings. Methods: A retrospective cohort study. The primary outcome measures were reintubation rate and mortality. Secondary outcome measures were location and indication for intubation, time until reintubation, total intubated days, ICU-stay, hospital-stay, 30-day in-hospital mortality, and overall in-hospital mortality. Results: A total of 336 outside-OR intubations were performed in 275 patients. Of those 275 patients, 51 (18.5%) were reintubated during the same hospital admission. (41%) of the reintubations occurred in a non-ICU setting. Reintubations occurred after up to 30-days after extubation. Most frequently between 7 and 30 days (32.8%, n = 20). Most of the reintubated patients were reintubated just once (56.9%; n = 29), but some were reintubated 2 times (29.4%; n = 15) or over 3 times (13.7%; n = 7). Reintubated patients had significant longer total ICU-stay (24 ± 3 days vs 12 ± 1 day, p <.001), hospital stay (37 ± 3 vs18 ± 1, p <.001), and total intubation days (8 ± 1 vs 7 ± 0.6, P <.02). The 30-day in-hospital mortality in reintubated patients was 13.7% (n = 7) compared to nonreintubated patients 35.9% (n = 80; P =.002). Conclusion: Reintubation was associated with a significant increase in hospital and ICU stay. The higher mortality rate among nonreintubated patients may indicate survival bias, in that severely sick patients did not survive long enough to attempt extubation. [ABSTRACT FROM AUTHOR]

Background: Nirmatrelvir/Ritonavir is an orally administered anti-SARS-Cov-2 drug used in mild-to-moderate COVID-19 patients. Our retrospective cohort study aims to evaluate the efficacy and safety of Nirmatrelvir/Ritonavir in severe hospitalized patients with Omicron infection, as well as in patients at high risk for progression to critical illness in real-world settings. Methods: A total of 350 patients received Nirmatrelvir/Ritonavir while 350 matched controls did not. Patients with confirmed COVID-19 were administered Nirmatrelvir 300 mg and Ritonavir 100 mg orally twice a day for 5 days, with the medication initiated on the first day after admission. The primary endpoint of the study was a composite outcome of hospitalization or death from any cause within 28 days. Secondary endpoints included the occurrence of adverse events and the evaluation of serum levels of IL-6 and viral load. Results: We documented the mortality risk from any cause within 28 days, viral load, serum IL-6 levels, and adverse events. Nirmatrelvir/Ritonavir reduced the 28-day risk of all-cause mortality by 86% (P =.011, hazard ratio (HR) = 0.14, 95% confidence interval (CI) = 0.03, 0.64). At baseline, the serum level of IL-6 was significantly higher in the antiviral treatment group compared to the control group (P <.001), but no significant difference (P =.990) was found between the two groups at discharge. In CKD patients undergoing hemodialysis, no significant worsening of renal function was observed in the Nirmatrelvir/Ritonavir treatment group compared to the control group. Conclusion: Nirmatrelvir/Ritonavir may reduce the 28-day risk of all-cause mortality in critically ill patients with COVID-19 and in patients at high risk for critical disease progression. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is often linked to chronic inflammation, which can be influenced by both lifestyle and dietary choices. However, the relationship between the inflammatory potential of diet and lifestyle factors and the risk of developing T2DM remains unclear. The present study aimed to investigate the associations of the empirical dietary inflammatory index (EDII), dietary inflammatory score (DIS), and lifestyle inflammatory score (LIS) with the risk of T2DM among Iranian adults. Methods: The current study was conducted on 5714 individuals from Yazd Health Study (YaHS) who were followed up for a mean period of six years. YaHS is a prospective cohort study which has been conducted since 2014. Dietary intakes were collected at baseline using the food frequency questionnaire. The relative risk (RR) of T2DM was calculated by Cox regression analysis across tertiles of EDII, DIS, and LIS, adjusted for potential confounders. Results: The mean ± SD for the age and body mass index of the study population were 47.0 ± 9.2 years and 26.7 ± 5.1 Kg.m2, respectively. A significant association between LIS and the risk of T2DM was observed (RR: 4.05, 95% CI: 2.61–6.27 P-trend < 0.001). Individuals in the highest compared to the lowest tertile of EDII-LIS (RR: 3.07, 95%CI: 2.01–4.68; P for trend < 0.001) and DIS-LIS (RR: 2.42, 95%CI: 1.69–3.49; P for trend < 0.001) had a higher risk of T2DM. However, no significant association was found between EDII and DIS scores and the risk of T2DM. Conclusion: Greater adherence to LIS, EDII-LIS, and DIS-LIS scores was associated with a higher risk of T2DM, while no significant association was found between EDII and DIS with T2DM risk. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the application of choledochoscopy combined with double-cannula lavage in the treatment of acute pancreatitis (AP) with encapsulated necrosis and analyzed related inflammatory indexes. Methods: Thirty patients with AP with encapsulated necrosis were enrolled and treated with choledochoscopy and double-cannula lavage. Serum white blood cell (WBC), procalcitonin (PCT), C-reactive protein (CRP), interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha (TNF-α), and related inflammatory indexes were detected before and after surgery. Results: All of the participants who underwent the surgery recovered well and were discharged without serious complications; no deaths occurred. The serum WBC, PCT, and CRP of patients after surgery decreased compared with before the procedure, and the differences in WBC and CRP were statistically significant (P < 0.05); the difference in PCT was not statistically significant (P > 0.05). Postoperatively, IL-6, IL-8, and TNF-α levels were higher than before surgery, and the differences were statistically significant (P < 0.05). Conclusion: The surgical method presented herein effectively controlled and alleviated the infection of patients; it also did not increase the risk of infection and can thus be considered a safe and effective surgical method. [ABSTRACT FROM AUTHOR]

• First systematic review looking at suPAR as a biomarker in a psychiatric population. • Primary analyses showed elevated suPAR levels in those with depressive disorder. • Secondary analysis showed elevated plasma suPAR levels in those with schizophrenia. • Two studies found no difference in serum suPAR levels between groups. • Chronic inflammatory dysregulation may contribute to the pathogenesis of these disorders. There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of chronic inflammation, which provides a more stable index of systemic inflammation than more widely used biomarkers. This review aims to synthesise studies that measured suPAR concentrations in individuals with a psychiatric disorder, to determine if these concentrations are altered in comparison to healthy participants. Comprehensive literature searches from inception to October 2023 were conducted of five relevant databases (PubMed, Web of Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses were performed to compare the standardised mean difference of blood suPAR levels (i.e. plasma or serum) for individuals with any psychiatric disorder relative to controls. Separate meta-analyses of suPAR levels were conducted for individuals with schizophrenia or other psychotic disorder and depressive disorder. Risk of bias was assessed using the Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding studies at high risk of bias, and analyses of studies that measured suPAR concentrations either in serum or in plasma separately. The literature search identified 149 records. Ten full-text studies were screened for eligibility and 9 studies were included for review. Primary analyses revealed no significant difference in suPAR levels between individuals with any psychiatric disorder compared to controls (k = 7, SMD = 0.42, 95 % CI [−0.20, 1.04]). However, those with depressive disorder had elevated suPAR levels relative to controls (k = 3, SMD = 0.61, 95 % CI [0.34, 0.87]). Similarly, secondary analyses showed no evidence of a significant difference in suPAR levels in individuals with any psychiatric disorder when studies at high risk of bias were excluded (k = 6, SMD = 0.54, 95 % CI [−0.14, 1.22]), but elevated suPAR concentrations for those with schizophrenia or other psychotic disorder were found (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). Furthermore, studies that analysed plasma suPAR concentrations found elevated plasma suPAR levels in individuals with any psychiatric disorder relative to controls (k = 5, SMD = 0.84, 95 % CI [0.38, 1.29]), while studies measuring serum suPAR levels in any psychiatric disorder did not find a difference (k = 2, SMD = -0.61, 95 % CI [−1.27, 0.04]). For plasma, elevated suPAR concentrations were also identified for those with schizophrenia or other psychotic disorder (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). When studies measuring either only serum or only plasma suPAR were considered, no significant difference in suPAR levels were observed between psychiatric disorder groups, although significantly elevated suPAR levels were detected in those with moderate to severe depressive disorder. However, plasma suPAR levels were significantly elevated in those with any psychiatric disorder relative to controls, while no difference in serum samples was found. A similar finding was reported for schizophrenia or other psychotic disorder. The plasma findings suggest that chronic inflammatory dysregulation may contribute to the pathology of schizophrenia and depressive disorder. Future longitudinal studies are required to fully elucidate the role of this marker in the psychopathology of these disorders. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma (GBM) is an aggressive form of brain cancer characterized by its poor prognosis due to its resistance and recurrence capabilities. Liquid biopsies have been increasingly utilized when studying GBM as they provide extensive amounts of data at multiple time points without the invasiveness of tissue samples. We used a large-scale proteomic panel from the serum of GBM patients collected before chemoradiation therapy (CRT) to study the connections of CD133, a protein recognized as involved in GBM resistance. We used a novel machine learning process to identify 24 proteins associated with CD133 and 12-month survival, successfully grouping patients into risk groups based on protein profiles. Our results identify a potentially harmful protein profile while revealing important serum associations of CD133. These identified proteins are possible prognostic indicators and treatment entry points with heightened value because they can be frequently traced and monitored. Glioma is the most prevalent type of primary central nervous system cancer, while glioblastoma (GBM) is its most aggressive variant, with a median survival of only 15 months when treated with maximal surgical resection followed by chemoradiation therapy (CRT). CD133 is a potentially significant GBM biomarker. However, current clinical biomarker studies rely on invasive tissue samples. These make prolonged data acquisition impossible, resulting in increased interest in the use of liquid biopsies. Our study, analyzed 7289 serum proteins from 109 patients with pathology-proven GBM obtained prior to CRT using the aptamer-based SOMAScan® proteomic assay technology. We developed a novel methodology that identified 24 proteins linked to both serum CD133 and 12-month overall survival (OS) through a multi-step machine learning (ML) analysis. These identified proteins were subsequently subjected to survival and clustering evaluations, categorizing patients into five risk groups that accurately predicted 12-month OS based on their protein profiles. Most of these proteins are involved in brain function, neural development, and/or cancer biology signaling, highlighting their significance and potential predictive value. Identifying these proteins provides a valuable foundation for future serum investigations as validation of clinically applicable GBM biomarkers can unlock immense potential for diagnostics and treatment monitoring. [ABSTRACT FROM AUTHOR]

Simple Summary: Supplementing trace minerals is common for managing bovine respiratory disease in developing beef cattle; however, its effects on their immune and metabolic systems are not fully understood. In this study, we evaluated three different mineral supplement programs and assessed their impact on the concentrations of copper, manganese, cobalt, and zinc, along with the whole blood gene expression, in high-risk beef cattle that remained clinically healthy over a 60-day period. Our results demonstrated that one supplement program, which included amino acid (organically) complexed minerals, led to an increase in gene activity related to adaptive immune system function and the metabolism of carbohydrates and fat-soluble vitamins compared to cattle-fed sulfate (inorganically) sourced complexed minerals. Additionally, the cattle given organically sourced minerals resulted in higher liver concentrations of copper at the end of the study compared to cattle given inorganically sourced minerals. This suggests that tailored mineral supplement programs may improve cattle immunity and mineral absorption. Understanding these effects improves how we manage cattle for diseases such as respiratory disease. Supplementing trace minerals is common in managing bovine respiratory disease (BRD) in post-weaned cattle; however, its influence on host immunity and metabolism in high-risk cattle remains unclear. We aimed to assess the impact of three supplementation programs on liver and serum trace element concentrations and blood gene expression. Fifty-six high-risk beef steers were randomly assigned to one of three groups over 60 days: (1) sulfate-sourced Cu, Co, Mn, and Zn (INR), (2) amino acid-complexed Cu, Mn, Co, and Zn (AAC), or (3) AAC plus trace mineral and vitamin drench (COMBO). Serum and liver biopsies for Cu, Co, Mn, and Zn at d0, d28, and d60 were analyzed from cattle free of BRD (n = 9 INR; n = 6 AAC; n = 10 COMBO). Differences and correlations of mineral concentrations were analyzed via generalized linear mixed models and Spearman's rank coefficients, respectively (p < 0.05). Whole blood RNA samples from healthy cattle (n = 4 INR; n = 4 AAC; n = 4 COMBO) at d0, d13, d28, d45, and d60 were sequenced and analyzed for differentially expressed genes (DEGs) via glmmSeq (FDR < 0.05), edgeR (FDR < 0.10), and Trendy (p < 0.10). Serum and liver Cu and Co concentrations increased over time in all groups, with higher liver Cu in COMBO (487.985 μg/g) versus AAC (392.043 μg/g) at d60 (p = 0.013). Serum and liver Cu concentrations (ρ = 0.579, p = 6.59 × 10−8) and serum and liver Co concentrations (ρ = 0.466, p = 2.80 × 10−5) were linearly correlated. Minimal gene expression differences were found between AAC versus COMBO (n = 2 DEGs) and INR versus COMBO (n = 0 DEGs) over time. AAC versus INR revealed 107 DEGs (d13–d60) with increased traits in AAC including metabolism of carbohydrates/fat-soluble vitamins, antigen presentation, ATPase activity, and B- and T-cell activation, while osteoclast differentiation and neutrophil degranulation decreased in AAC compared to INR. Our study identifies gene expression differences in high-risk cattle fed inorganic or amino acid-complexed mineral supplements, revealing adaptive immune and metabolic mechanisms that may be improved by organically sourced supplementation. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two major neurodegenerative diseases causing dementia. Due to similar clinical phenotypes, differential diagnosis is challenging without specific biomarkers. Beta-site Amyloid Precursor Protein cleaving enzyme 1 (BACE1) is a β-secretase pivotal in AD pathogenesis. In AD and mild cognitive impairment subjects, BACE1 activity is increased in brain/cerebrospinal fluid, and plasma levels appear to reflect those in the brain. In this study, we aim to evaluate serum BACE1 activity in FTD, since, to date, there is no evidence about its role. The serum of 30 FTD patients and 30 controls was analyzed to evaluate (i) BACE1 activity, using a fluorescent assay, and (ii) Glial Fibrillary Acid Protein (GFAP) and Neurofilament Light chain (NfL) levels, using a Simoa kit. As expected, a significant increase in GFAP and NfL levels was observed in FTD patients compared to controls. Serum BACE1 activity was not altered in FTD patients. A significant increase in serum BACE1 activity was shown in AD vs. FTD and controls. Our results support the hypothesis that serum BACE1 activity is a potential biomarker for the differential diagnosis between AD and FTD. [ABSTRACT FROM AUTHOR]

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates. Through bioinformatic pathway enrichment and network analysis, we reveal associations of differentially abundant proteins with cytoskeletal, metabolic, and ribosomal activities, all of which have been previously associated with prostate cancer progression. Additionally, optimized machine learning classifier analysis reveals proteomic signatures capable of detecting the disease prior to biopsy, performing on par with an accepted clinical risk calculator benchmark. [ABSTRACT FROM AUTHOR]

Platelet-rich fibrin (PRF) is prepared by spontaneous coagulation of fractionated blood. When squeezed between two plates, PRF is separated into solid PRF membranes and a liquid exudate, the PRF serum. The question arises regarding how much the overall activity remains in the PRF membranes and what is discarded into the PRF serum. To this end, we have exposed gingival fibroblasts to lysates prepared from PRF membranes and PRF serum, followed by bulk RNA sequencing. A total of 268 up- and 136 down-regulated genes in gingival fibroblasts exposed to PRF membrane lysates were significantly regulated under the premise of a minimum log2 with 2.5-fold change and a minus log10 significance level of two, respectively. PRF serum only caused 62 up- and 32 down-regulated genes under these conditions. Among the 46 commonly up-regulated genes were CXCL1, CXCL5, CXCL6, CXCL8, IL33, IL6, and PTGS2/COX2, stanniocalcin-1—all linked to an inflammatory response. PRF membrane lysates further increased chemokines CCL2, CCL7, CXCL2, CXCL3, and IL1R1, IL1RL1, and IL1RN, as well as the paracrine factors IL11, LIF, IGF1, BMP2, BMP6, FGF2, and CCN2/CTGF, and all hyaluronan synthases. On the other hand, PRF serum increased DKK1. The genes commonly down-regulated by PRF membrane lysates and PRF serum included interferon-induced protein with tetratricopeptide repeats (IFIT1, IFIT2, IFIT3) and odd-skipped-related transcription factors (OSR1 and OSR2), as well as FGF18 and GDF15, respectively. Taken together, PRF membrane lysates, compared to PRF serum, cause a more complex response in gingival fibroblasts, but each increased chemokine expression in gingival fibroblasts. [ABSTRACT FROM AUTHOR]

Serum biochemical indicators serve as vital proxies that reflect the physiological state and functions of different organs. The genetic parameters and molecular mechanisms underlying serum biochemical indicators of sheep (Ovis aries) have not been well understood. Therefore, the aim of the present study was to identify the genetic architecture and genomic loci underlying ten serum biochemical indicators in sheep, including alanine transaminase, aspartate transferase, lactate dehydrogenase, cholesterol, glucose, phosphorus, calcium, creatinine, urea and total protein levels. We implemented genetic parameter estimations and GWASs for each trait in 422 Akkaraman lambs. Overall, low to moderate heritability estimates were found in the range of 0.14–0.55. Additionally, low to high genetic correlations were observed among traits. In total, 23 SNP loci were associated with serum biochemical indicators leading to 19 genes. These were SPTA1, MGST2, CACUL1, IGFBP7, PARD3, PHB1, SLC15A5, TRIM35, RGS6, NUP93, CNTNAP2, SLC7A11, B3GALT5, DPP10, HST2ST1, NRP1, LRP1B, MAP3K9 and ENSOARG00020040484.1, as well as LOC101103187, LOC101117162, LOC105611309 and LOC101118029. To our knowledge, these data provide the first associations between SPTA1 and serum cholesterol and between ENSOARG00020040484.1 and serum glucose. The current findings provide a comprehensive inventory of the relationships between serum biochemical parameters, genetic variants and disease-relevant characteristics. This information may facilitate the identification of therapeutic targets and fluid biomarkers and establish a strong framework for comprehending the pathobiology of complex diseases as well as providing targets for sheep genetic improvement programs. [ABSTRACT FROM AUTHOR]

Phthalate plasticizers (PAEs) illegally used in food pose a great threat to human health. A new and efficient sensing platform for the sensitive detection of the PAE residues in biological fluids needs to be designed and developed. Here, we report a simple and reliable surface-enhanced Raman spectroscopy (SERS) active platform with extralong hot spots of Au nanobipyramids@Ag nanorods (Au NBPs@Ag NRs) for the rapid and sensitive detection of PAEs in biological fluids. To achieve high activity, Au NBPs@Ag NRs with different shell lengths were fabricated by controlling the synthesis conditions, and the corresponding SERS properties were investigated by using crystal violet (CryV) and butyl benzyl phthalate (BBP). The experimental results showed that a longer shell length correlated to greater Raman activity, which was confirmed by finite-difference time-domain (FDTD) electromagnetic simulation. More importantly, the extralong hot spots of the Au NBPs@Ag NR SERS-active substrate showed excellent homogeneity and reproducibility for the CryV probe molecules (6.21%), and the detection limit was 10−9 M for both BBP and diethylhexyl phthalate (DEHP). Furthermore, through the standard addition method, an extralong hot spots SERS substrate could achieve highly sensitive detection of BBP and DEHP in serum and tears fluids, and the detection limit was as low as 3.52 × 10−8 M and 2.82 × 10−8 M. Therefore, the Au NBPs@Ag NR substrate with an extraordinarily long surface is efficient and versatile, and can potentially be used for high-efficiency sensing analysis in complex biological fluids. [ABSTRACT FROM AUTHOR]