Abstract Background The accurate measurement of serum steroid hormone levels is important in many endocrinologic diseases, including but not limited to congenital adrenal hyperplasia (CAH). Screening for CAH with 17-OH-progesterone immunoassays is known to yield many false-positive results. Furthermore, the differentiation between classical CAH and other non-classical CAH subtypes requires complex steroid profiling. We developed and evaluated the analytical performance of a simultaneous multiplex LC-MS/MS assay for 20 steroid hormones, and also established preliminary pediatric reference intervals for the evaluated steroid hormones. Methods Briefly, sample preparation consists of serum sample mixing with internal standard and acetonitrile, followed by lipid extraction with methyl-tert-butyl ether. Derivatization is conducted using hydroxylamine. The LC-MS/MS system consists of an ACQUITY UPLC I-Class System (Waters Corporation, Milford, MA, USA) equipped with a Waters ACQUITY UPLC BEH C18 column (1.0×50 mm, 1.7 µm; Waters Corporation), and Xevo TQ-XS (Waters Corporation) MS/MS system. The linearity, within- and between-run precision, carryover, lower limits of detection (LOQ) and quantification (LOQ), and matrix effect/recovery were evaluated for aldosterone, cortisol, cortisone, 21-deoxycortisol, corticosterone, 11β-OH-testosterone, 11-ketotestosterone, 11-ketoandrostendione, 11β-OH-androstenedione, estrone, 11-deoxycortisol, 17-OH-pregnenolone, 11β-OH-progesterone, Dehydroepiandrosterone (DHEA), androstenedione, 11-deoxycorticosterone, testosterone, 17-OH-progesterone, 5α-dihydrotestosterone, pregnenolone, and progesterone. Depending on the analyte, approximately 40 residual pediatric samples (age <9 years) were used to calculate the 2.5 and 97.5 percentiles in order to establish reference intervals. Results Linearity evaluation showed correlation coefficients (R2) of >0.9900 for 19/20 hormones, and 0.9853 for corticosterone. Within-run precision (%CV) ranged from 2.24-13.04%, 3.30-12.27%, and 2.63-9.67% for low, medium, and high steroid hormone levels. Between-run precision (%CV) ranged from 3.91-23.86%, 2.97-27.35%, and 3.95-23.67% for low, medium, and high steroid hormone levels. Carryover (%) was <5% for 18/20 hormones, 6.61% for pregnenolone, and 8.24% for progesterone. LOD ranged from 0.005-0.25 ng/mL, and LOQ ranged from 0.01-0.5 ng/mL for all 20 hormones. Matrix effect ranged from 99.0-110.6% for all 20 hormones, and recovery was 69.4-88.1% for 19/20 hormones, and 59.7% for aldosterone. Preliminary reference intervals (2.5-97.5 percentile) were successfully established for 18/20 evaluated hormones (ng/mL): aldosterone (0.010-0.186), cortisol (23.4-80.8), cortisone (5.82-24.8), 21-deoxycortisol (0.130-0.226), corticosterone (0.088-1.501), 11β-OH-testosterone (0.001-0.021), 11-ketotestosterone (0.031-0.390), 11-ketoandrostendione (0.031-0.390), 11β-OH-androstenedione (0.024-0.279), 11-deoxycortisol (0.040-0.701), 17-OH-pregnenolone (0.112-1.994), 11β-OH-progesterone (0.001-0.316), DHEA (0.018-1.452), androstenedione (0.010-0.160), 11-deoxycorticosterone (0.016-0.175), testosterone (0.015-0.096), 17-OH-progesterone (0.020-0.251), pregnenolone (0.031-0.215), and progesterone (0.010-0.048). Conclusions The LC-MS/MS-based multiplex steroid hormone assay showed robust analytical performance for all evaluated parameters, and can be used to reliably measure 20 steroid hormones with good sensitivity and specificity. This assay can be utilized in the clinical laboratory for the accurate diagnosis of various endocrinologic diseases, including rare subtypes of CAH, which can ultimately lead to better clinical outcomes.

Abstract Background A 9-month-old infant presented with developmental motor delay. Comprehensive evaluation including microarray and brain MRI revealed no specific abnormalities except for hypotonicity. The patient's perinatal history, including newborn screening test (NST), showed no remarkable findings. Additionally, the infant exhibited facial dysmorphism and microcephaly, leading to another NST to explore potential metabolic diseases. Upon NST, Thyroid-Stimulating Hormone (TSH) levels were 1.86 and 1.27 mlU/L (duplicate testing results; reference value: <12 mlU/L), 17-Hydroxyprogesterone (17-OHP) levels were 0.55 and 0.48 ng/mL (duplicate testing results; reference value adjusted for body weight: <5.0 ng/mL), and total Galactose (Gal) and Galactose-1-Phosphate (Gal-1-P) levels were 1.68 mg/dL (reference value: <8 mg/dL). Methods Upon inspection of the dried blood spot (DBS) sample, the DBS used for the tests partially appeared to be inadequately collected on the absorbent filter paper, which could cause errors related to the disc and specimen itself. Consequently, re-sampling and re-testing were necessary to ensure accuracy. A second NST was performed with the new DBS samples. In the second NST results, most parameters were within the allowable ranges. However, the TSH levels were notably below the detectable limit (<0.7 mlU/L), and the 17-OHP levels were significantly elevated at 332ng/mL, diverging markedly from the initial NST results. To ensure reliability of the measured test results, TSH levels were analyzed using both the existing PerkinElmer equipment and compared with results from a Cobas 8000 system (Roche) and mass spectrometry. Similarly, 17-OHP levels were also compared using mass spectrometry. Results Upon comparing the TSH results, both analytical methods (PerkinElmer and Roche) yielded identical outcomes. However, significant discrepancy was observed when compared to mass spectrometry results. Review of the relevant testing batches showed no significant quality control issues with the NST, leading to clinical suspicion of ethylene-diamine-tetraacetic acid (EDTA)-induced interference. According to existing literature, when NST are conducted using the lanthanide fluorescence method, distortions can occur in DBS containing EDTA, depending on the concentration of EDTA present. In such cases, the EDTA-induced interference may result in false-negative TSH and false-positive 17-OHP results. These discrepancies can be differentiated using standard MS/MS testing. With regards to our case, upon enquiry, the second DBS sample was revealed to be collected from an existing EDTA sample rather than directly from the patient. Thus, adequate DBS discs from the initial sample were obtained and re-analyzed for NST using mass spectrometry, with final results reporting no specific abnormalities. Conclusions The discrepancies observed in TSH and 17-OHP levels between the first and second set of DBS samples were found to be unrelated to other laboratory factors, such as quality control issues. Instead, they were conclusively identified as false-negative and false-positive results associated with interference due to the use of EDTA-containing collection bottles. Mass spectrometry analysis was able to confirm the interference. Clinical awareness should be promoted in order to prevent EDTA-induced interference in NST.

Although colorectal cancer (CRC) survivors often suffer from defecation related symptoms (DRS), there are very few treatment options to improve DRS. Strengthening of abdominal muscles to increase intra-abdominal pressure and pelvic floor exercises to improve pelvic floor dyssynergia may improve DRS in colorectal cancer patients. However, the effects of exercise on DRS have not been studied fully. Therefore, the purpose of this study is to investigate the efficacy of exercise on DRS in CRC. A total of 120 CRC who completed surgery and adjuvants therapy were recruited out of 441 approached. 120 participants were randomly assigned to either exercise (EG) or usual care group (CG). The combined weekly supervised and home-based exercise program (12 weeks) includes increase in physical activity (PA) levels to meet the ACSM guideline as well as daily calisthenics exercises. Calisthenics exercises include a total of 12 movements aimed to increase whole body muscle strengths which focused on core and pelvic floor muscles. The primary outcome was DRS score assessed the sum of blood and mucus in stool, stool frequency, abdominal pain, buttock pain, bloating, flatulence, fecal incontinence and embarrassment in EOTRC-QLQ-CR29. A two-way ANOVA repeated measures were used determine group and time interaction.Table: 581PEffects of exercise on defecatory symptomsControlExercisep-valuePrePostPrePostBlood in stool4.7 ± 9.74.4 ± 9.17.2 ± 15.53.1 ± 8.90.05Stool frequency26.3 ± 27.020.1 ± 20.528.7 ± 25.123.4 ± 23.80.91Abdominal pain14.4 ± 22.411.7 ± 19.218.3 ± 24.910.0 ± 16.60.21Buttock pain12.2 ± 21.212.8 ± 25.418.9 ± 30.312.8 ± 26.10.08Bloating22.8 ± 22.525.0 ± 25.834.4 ± 30.722.8 ± 27.10.01Flatulence21.0 ± 26.017.7 ± 23.328.3 ± 33.521.5 ± 25.10.42Fecal incontinence13.5 ± 20.513.1 ± 20.516.9 ± 24.812.9 ± 25.30.26Embarrassment20.4 ± 26.816.7 ± 20.827.6 ± 32.018.0 ± 25.50.16Bolds were statistically significant different between pre and post (p<.05), p= Difference between control vs. exercise Open table in a new tab Bolds were statistically significant different between pre and post (p<.05), p= Difference between control vs. exercise Among the 120 participants enrolled, 100 (96.6%) completed the trial with supervised exercise compliance rate of 95%. PA levels increased and fitness levels improved only in the exercise group. Exercise significantly decreased DRS score (6 week - 0 week: CG= -14.0 ± 54.7 vs. EG= - 56.1 ± 99.5, p for group and time interaction = 0.02). Symptom scores in EG include blood and mucus in stool, abdominal pain, buttock pain, bloating, flatulence and embarrassment were improved. It is concluded that both combined supervised and home-based exercise significantly reduced bowel and defecatory problems in colorectal cancer patients.

Breast cancer surgery can impair shoulder function, and the effects of rehabilitation exercise during early recovery remain uncertain. This study aims to assess the effectiveness of tailored exercise intervention on shoulder function recovery at one and six months post-surgery. A total of 122 breast cancer patients (Stage 0-3) scheduled for surgery were evaluated, and 58 patients (mean age 50.2±6.6 years) were randomly assigned to an exercise or usual care group (1:1). The exercise group underwent five tailored exercise education sessions, starting one day before hospital discharge and continuing for four weeks after surgery. Participants received exercise diaries, online links, and QR codes for home-based workouts. The primary outcome measured the proportion of participants achieving 90% of their pre-surgery shoulder ROM and strength at one and six months post-surgery. Secondary measures included DASH and SPADI scores, physical activity levels, and body composition. Out of 58 participants, 56 (96.6%) completed the trial, with a 96.6% exercise compliance rate one month after surgery. In the exercise group, 92.9% and 96.2% achieved pre-surgery shoulder strength levels at one and six months post-surgery, respectively, compared to 3.7% and 32.1% in the control group. The exercise group also exhibited significantly lower shoulder pain and disability scores (SPADI) at one and six months after surgery, as well as higher physical activity levels at six months.Table: 345PChange in shoulder strength among postoperative breast cancer patientsAffected armEPET (n=25)Usual Care (n=26)pSum of strength (Ib) T044.1±10.247.5±11.10.36 T123.2±10.3∗∗∗23.8±9.4∗∗∗0.80 T240.4±11.928.5±11.9∗∗∗0.001 T345.9±14.732.0±11.2∗∗∗<0.001 T451.3±14.032.0±9.2∗∗∗<0.001 T561.0±17.1∗∗∗38.3±8.4∗∗∗<0.001Mean±SD, P=represented the results of independent T-test (the p-value adjusted for Bonferroni method (0.05/6=0.0083), *=represented paired t-test [**p<0.01 vs. baseline, ***p<0.001 vs. baseline (p-value adjusted for Bonferroni method)] Abbreviation: early postoperative exercise therapy; EPET Open table in a new tab . Mean±SD, P=represented the results of independent T-test (the p-value adjusted for Bonferroni method (0.05/6=0.0083), *=represented paired t-test [**p<0.01 vs. baseline, ***p<0.001 vs. baseline (p-value adjusted for Bonferroni method)] Abbreviation: early postoperative exercise therapy; EPET Early implementation of tailored exercise during rehabilitation significantly improved shoulder function beyond pre-surgery levels. This study provides essential insights into the efficacy and safety of early rehabilitation exercises for breast cancer patients during the post-surgery recovery phase.

Although engaging in exercise after breast cancer surgery (BCS) has been shown to facilitate faster recovery, factors influencing exercise participation during the early recovery phase remain unclear in breast cancer patients. Therefore, this study aimed to explore the perceptions, attitudes, and barriers to exercise in breast cancer patients immediately after surgery and up to 4 weeks post-surgery. A descriptive qualitative research method was employed to investigate this topic. A purposive sample of 33 breast cancer patients was selected, and each participant was interviewed three times over a one-month period after surgery. We found physical constraints and psychological resistance were identified as barriers to exercise. Postoperative physical symptoms (pain, range of motion, lack of fitness, and seroma) and surgical drains were identified as physical constraints. Participants also faced psychological resistance such as concerns about side effects, lack of willpower, and fear of pain. Furthermore, a lack of trustworthy information regarding the timing of exercise initiation and proper types of exercise after surgery was identified as a psychological resistance.Table: 359PThemes, codes, and categories from the interviewsCategories%(n)Codes%(n)Theme%(n)Physical constraints100% (33)Postoperative physical symptoms100% (33)Pain at the surgery site87.9% (29)Limited range of motion66.6% (22)Lack of fitness33.3% (11)Seroma12.2% (4)Operation derived condition45.4% (15)Drain45.5% (15)Psychological resistance48.5% (16)Perception and attitude54.5% (18)Concerns about side effects42.4% (13)Lack of willpower15.2% (5)Fear of pain15.2% (5)Concerns due to lack of trustworthy exercise information54.5% (18)Concerns regarding the exercise timing being inappropriate42.4% (14)Discouragement from others18.2% (6) Open table in a new tab The identified barriers, both physical and psychological, should be taken into consideration when developing strategies to motivate and support patients in engaging in exercise. The identified barriers, both physical and psychological, should be taken into consideration when developing strategies to motivate and support patients in engaging in exercise.

We report an observation of new bottom baryons produced in p (cid:1) p collisions at the Tevatron. Using 1 : 1 fb (cid:2) 1 of data collected by the CDF II detector, we observe four (cid:2) 0 b (cid:1) (cid:3) resonances in the fully reconstructed decay mode (cid:2) 0 b ! (cid:2) (cid:4) c (cid:1) (cid:2) , where (cid:2) (cid:4) c ! pK (cid:2) (cid:1) (cid:4) . We interpret these states as the (cid:3) (cid:5)(cid:1)(cid:6)(cid:3) b baryons and measure the following masses: m (cid:3) (cid:4) b (cid:7) 5807 : 8 (cid:4) 2 : 0 (cid:2) 2 : 2 (cid:5) stat : (cid:6) (cid:3) 1 : 7 (cid:5) syst : (cid:6) MeV =c 2 , m (cid:3)

OBJECTIVE To assess associations between parameters derived from F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and mRNA expression levels of immune checkpoint biomarkers such as programmed death receptor 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4) as well as tumor mutation burden (TMB) in non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Integrated data were downloaded from Genomic Data Common Data Portal. Clinical, mRNA-seq, and whole exome-seq data of lung adenocarcinoma and squamous cell carcinoma from The Cancer Genome Atlas (TCGA) database were analyzed. TMB was defined as the total number of somatic missense mutations per megabase of the genome examined. Expression levels of PD-1, PD-L1, CTLA4 mRNA and TMB were collected. Correlations between imaging parameters of glucose metabolism and the expression levels of genomic biomarkers from cancers were evaluated. Bonferroni correction (adjusted p<0.0027) was applied to reduce type 1 error. RESULTS Of 31 NSCLC cases, 11 cases were adenocarcinoma (LUAD) and 20 were squamous cell carcinoma (LUSC). In linear regression analysis, texture parameters such as low gray-level run emphasis (LGRE, R2=0.48, p<0.0001), short run low gray-level emphasis (SRLGE, R2=0.45, p<0.0001) and long run low gray-level emphasis (LRLGE, R2=0.41, p=0.0001) derived from gray-level run length matrix (GLRLM) showed remarkable correlation with PD-L1 mRNA expression. Expression of PD-1, CTLA-4, and TMB failed to show any significant correlation with parameters of the F-18 FDG PET/CT. CONCLUSIONS Texture parameters derived from PET, known to indicate glucose uptake distribution, were correlated with expression of PD-L1 mRNA but not with expression of PD-1, CTLA-4 and TMB. Thus, tumoral heterogeneity could be a surrogate marker for the identification of PD-L1 level in NSCLC.

A reasonable, high sensitive and accurate analytical method for the determination of 20 allergenic disperse dyes in foodstuffs was developed and validated. The obtained results showed that an ultra high liquid performance chromatography system – equipped with tandem quadrupole mass spectrometry (UHPLC–MS/MS) proved to be ideal for the selected method enabling multidimensional processing of the samples. Under optimized conditions, validation results showed excellent linearity (5–1000 µg/L, r2 ≥ 0.997), limits of detection (LODs, 1.1–10.8 μg/kg), recoveries (60.2–110.3%) and precision (RSDs ≤ 12.6%) for the twenty disperse dyes under investigation. The developed method was successfully applied to the analysis of 20 disperse dyes in real foodstuffs demonstrating the validity and applicability of the current method for continuing monitoring of the selected dyes. The proposed UHPLC-MS/MS is thus proved to be a convenient, effective, sensitive and timesaving method for the isolation and determination of allergenic disperse dyes in edible packaging and other foodstuffs.

The photocatalytic ozonation of oxamic acid (OMA) on an aqueous solution in the presence of carbon nitride was investigated as an efficient process of water treatment. Several techniques were used to characterize the fresh and used catalysts. The bulk material, labeled as gCN, was thermally post-treated at 500 °C (gCN-T), and a significant enhancement in the surface area was observed. Photocatalytic ozonation in the presence of carbon nitride proved to be effective in removing OMA, especially using gCN-T, owing to a complete OMA degradation after 120 min of reaction. The combined performance of photocatalytic ozonation in the presence of gCN-T allowed to confirm a synergetic effect between the two processes. The decrease in the OMA removal rate observed in the presence of scavengers suggested that the photogeneration of holes on the catalyst surface is predominant for the oxidation mechanism when compared to the hydroxyl radicals. A slight decrease in the degradation performance was observed in the recycling tests, probably owing to the modifications on gCN-T exposed structure; the other physical-chemical properties remained constant after several runs of photocatalytic ozonation.

Introduction: The multi-array tDCS has been introduced as a very effective tDCS montage for precisely targeting the ROI. Since increasing the number of electrodes increases the degree of freedom, tDCS efficiency is the best, in theory, when the maximum number of electrodes is used, however, many electrodes make practical applications difficult. Thus, we investigated the efficiencies of multi-array tDCS in terms of intensity and focality when the maximum number of electrodes using multi-array tDCS varies.

Calcium is vital to many aspects of human biology. For example, calcium is involved in intracellular and intercellular signal transmissions, muscular contraction, coagulation, and bone biology. The body has developed intricate regulatory pathways to ensure a narrow range of concentrations of ionized calcium in the plasma, free calcium in the cytoplasm, calcium incorporation into bone, and calcium absorption by the gastrointestinal tract. Tightly linked to calcium homeostasis are the regulation of plasma phosphate and the incorporation of phosphate into bone together with calcium. From a biodynamic viewpoint, phosphate-containing compounds and their breakdown are critical in facilitating nearly all energy-dependent cellular processes. Likewise, magnesium (e.g., hypomagnesemia) can impact calcium biology. Magnesium is necessary for normal parathyroid hormone (PTH) release and response to PTH. After providing an introductory discussion of calcium biology, this chapter deals with three major topics: [i] hypocalcemia, [ii] hypercalcemia, and [iii] monitoring of bone turnover.

We examined the correlation between thyroid hormone (TH) concentrations and the serum fibroblast growth factor 21 (FGF21) concentration in septic patients and to assess the collaborative value of these factors in predicting 28-day mortality in septic patients.A total of 120 consecutive patients with sepsis were divided into two groups according to their survival or death within 28 days after initial diagnosis of sepsis.Patients in the non-survivor group had significantly higher serum FGF21 concentrations but lower total and free triiodothyronine (T3) and tetraiodothyronine (T4) concentrations than those in the survivor group. Thyroid hormone concentrations, including T3, free T3, T4 and free T4, were significantly negatively correlated with the ∆SOFA and APACHE II scores as well as the serum FGF21, IL-6, tumor necrosis factor-α, IL-10, procalcitonin, and C-reactive protein concentrations. Logistic regression analysis showed that the ∆SOFA score, serum FGF21 concentration, and free T3 concentration were significant predictors of 28-day mortality. The model with variables of ∆SOFA score and serum FGF21 and free T3 concentrations had the greatest area under the curve of 0.969.The addition of free T3 and serum FGF21 to ∆SOFA score provided a significantly improved ability to predict 28-day mortality in septic patients.

Transcranial direct current stimulation (tDCS) is known to modulate the neuronal excitability. Various tDCS studies have been attempted to modulate brain functions such as cognitive ability, motor function, and so on. However, behavioral performance as the evidence of induced effects by tDCS has been mainly reported. For better understanding the tDCS-induced effects, it is necessary to investigate the brain activity changes. In this study, we investigated the effect of tDCS on mental arithmetic capacity, which is one of the high-order cognitive function, with MEG.

In the fall 2016, GeantV went through a thorough community evaluation of the project status and of its strategy for sharing the R&D results with the LHC experiments and with the HEP simulation community in general. Following this discussion, GeantV has engaged onto an ambitious 2-year road-path aiming to deliver a beta version that has most of the final design and several performance features of the final product, partially integrated with some of the experiment's frameworks. The initial GeantV prototype has been updated to a vector-aware concurrent framework, which is able to deliver high-density floating-point computations for most of the performance-critical components such as propagation in field and physics models. Electromagnetic physics models were adapted for the specific GeantV requirements, aiming for the full demonstration of shower physics performance in the alpha release at the end of 2017. We have revisited and formalized GeantV user interfaces and helper protocols, allowing to: connect to user code, provide recipes to access efficiently MC truth and generate user data in a concurrent environment.