Response Status Research Articles

OMIP-107: 8-color whole blood immunophenotyping panel for the characterization and quantification of lymphocyte subsets and monocytes in swine.

We developed this whole blood immunophenotyping panel with the aim to monitor and quantify major lymphocyte subsets (CD4+, CD8+, CD4+CD8+ αβ T cells, γδ-T cells, B and NK cells) and monocytes in pigs. The panel involved the use of commercially available reagents, avoiding secondary antibody staining or in-house antibody conjugations, with the aim to make the assay accessible and reproducible across laboratories. The assay is accurate, robust and represents a useful tool for immune monitoring of swine in the pharmacology and toxicology fields, or to monitor the immune status in response to vaccination and diseases.

Informing future randomized controlled trials of amantadine hydrochloride in neurocritical care and post-neurocritical care stroke patients through a retrospective study

BackgroundAmantadine hydrochloride has been increasingly prescribed as a neurostimulant for neurocritical care stroke patients to promote wakefulness during inpatient recovery. However, a lack of guidelines makes it difficult to decide who may benefit from this pharmacotherapy and when amantadine should be initiated during the hospital stay. This study aims to determine some factors that may be associated with favorable response to amantadine to inform future randomized controlled trials of amantadine in critical care or post-critical care stroke patients.MethodsRetrospective chart review for this study included neurocritical care and post-neurocritical care patients with acute ischemic or hemorrhagic stroke who were started on amantadine (N = 34) in the years 2016–2019. Patients were labeled as either responders or nonresponders of amantadine within 9 days of initiation using novel amantadine scoring criteria utilized and published in Neurocritical Care in the year 2021, which included spontaneous wakefulness and Glasgow Coma Scale (GCS). Amantadine response status and predictive variables were analyzed using nonparametric tests and adjusted multivariable regression models.ResultsThere were large but nonsignificant variations in the median total milligrams of amantadine received in the first 9 days (IQR = 700-1,450 mg, p = 0.727). GCS on the day before amantadine initiation was significantly higher for responders (median = 12, IQR = 9–14) than nonresponders (median = 9, IQR = 8–10, p = 0.009). Favorable responder status was significantly associated with initiation in the critical care unit versus the step-down unit or the general medical/surgical floor [\U0001d6c3=1.02, 95% CI (0.10, 1.93), p = 0.031], but there was no significant associations with hospital day number started [\U0001d6c3=-0.003, 95% CI (-0.02, 0.02), p = 0.772].ConclusionsFuture randomized controlled trials of amantadine in hospitalized stroke patients should possibly consider examining dose-dependent relationships to establish stroke-specific dosing guidelines, minimum GCS threshold for which amantadine is efficacious, and the impact of patients’ determined level of acuity on clinical outcomes instead of solely examining the impact of earlier amantadine initiation by hospital day number. Future research with larger sample sizes is needed to further examine these relationships and inform future clinical trials.

Synergistic effects of dietary selenium nanoparticles and vitamin C improve growth performance, immune response, and antioxidant status of juvenile common carp (Cyprinus carpio)

IntroductionThis study aimed to investigate the synergistic effects of dietary selenium nanoparticles (Se-NPs) and vitamin C (VC) on growth, body composition, antioxidant defense, immunity, and serum biochemical indexes of common carp (Cyprinus carp) juveniles. MethodologyThe test diets were supplemented with three levels of Se-NPs (0, 0.5, and 1 mg/Kg) and three levels of VC (0, 500, and 1000 mg/Kg): the basal diet without supplemental Se-NPs and VC (VC0SeNPs0; control), 0.5 mg Se-NPs /Kg (VC0SeNPs0.5), 1 mg Se-NPs /Kg (VC0SeNPs1), 500 mg VC/Kg (VC500SeNPs0), 1000 mg VC/Kg (VC1000SeNPs0), 500 mg VC/Kg and 0.5 mg Se-NPs (VC500SeNPs0.5), 1000 mg VC/Kg and 0.5 mg Se-NPs (VC1000SeNPs0.5), 500 mg VC/Kg and 1 mg Se-NPs (VC500SeNPs1), 1000 mg VC/Kg and 1 mg Se-NPs (VC1000SeNPs1). The fish were randomly divided into nine experimental groups in triplicate tanks per treatment and fed on their respective diets for 60 days. ResultsThe findings displayed that fish fed with VC500SeNPs1 and VC500SeNPs0.5 diets had significantly (P < 0.05) higher specific growth rates when compared to other groups. The lowest feed conversion ratio was detected in the VC1000SeNPs1 group and the highest in the control group (P < 0.05). VC, Se-NPs, and their interaction had no significant effect on serum malondialdehyde, ACH50, and IgM (P > 0.05). However, the best parameters associated with antioxidant capacity (higher serum levels of superoxide dismutase and total reduced glutathione) and physiological status (higher concentration of serum globulin and lower amounts of aspartate aminotransferase and lactate dehydrogenase) belonged to the VC1000SeNPs1 and VC500SeNPs1 groups. The results suggest that the Se-NPs and VC combination more efficiently influence the common carp’s growth performance, antioxidant status, immunity, and physiological parameters. ConclusionOverall, the diet enriched with 500 mg VC and 1 mg Se-NPs /Kg (VC500SeNPs1) is suitable for boosting the growth and immunity of common carp.

Hyperspectral Estimation of Chlorophyll Content in Wheat under CO2 Stress Based on Fractional Order Differentiation and Continuous Wavelet Transforms

The leaf chlorophyll content (LCC) of winter wheat, an important food crop widely grown worldwide, is a key indicator for assessing its growth and health status in response to CO2 stress. However, the remote sensing quantitative estimation of winter wheat LCC under CO2 stress conditions also faces challenges such as an unclear spectral sensitivity range, baseline drift, overlapping spectral peaks, and complex spectral response due to CO2 stress changes. To address these challenges, this study introduced the fractional order derivative (FOD) and continuous wavelet transform (CWT) techniques into the estimation of winter wheat LCC. Combined with the raw hyperspectral data, we deeply analyzed the spectral response characteristics of winter wheat LCC under CO2 stress. We proposed a stacking model including multiple linear regression (MLR), decision tree regression (DTR), random forest (RF), and adaptive boosting (AdaBoost) to filter the optimal combination from a large number of feature variables. We use a dual-band combination and vegetation index strategy to achieve the accurate estimation of LCC in winter wheat under CO2 stress. The results showed that (1) the FOD and CWT methods significantly improved the correlation between the raw spectral reflectance and LCC of winter wheat under CO2 stress. (2) The 1.2-order derivative dual-band index (RVI (R720, R522)) constructed by combining the sensitive spectral bands of the CO2 response of winter wheat leaves achieved a high-precision estimation of the LCC under CO2 stress conditions (R2 = 0.901). Meanwhile, the red-edged vegetation stress index (RVSI) constructed based on the CWT technique at specific scales also demonstrated good performance in LCC estimation (R2 = 0.880), verifying the effectiveness of the multi-scale analysis in revealing the mechanism of the CO2 impact on winter wheat. (3) By stacking the sensitive spectral features extracted by combining the FOD and CWT methods, we further improved the LCC estimation accuracy (R2 = 0.906). This study not only provides a scientific basis and technical support for the accurate estimation of LCC in winter wheat under CO2 stress but also provides new ideas and methods for coping with climate change, optimizing crop-growing conditions, and improving crop yield and quality in agricultural management. The proposed method is also of great reference value for estimating physiological parameters of other crops under similar environmental stresses.

Patient-derived acellular ascites fluid affects drug responses in ovarian cancer cell lines through the activation of key signalling pathways.

Malignant ascites is commonly produced in advanced epithelial ovarian cancer (EOC) and serves as unique microenvironment for tumour cells. Acellular ascites fluid (AAF) is rich in signalling molecules and has been proposed to play a role in the induction of chemoresistance. Through in vitro testing of drug sensitivity and by assessing intracellular phosphorylation status in response to mono- and combination treatment of five EOC cell lines after incubation with AAFs derived from 20 different patients, we investigated the chemoresistance-inducing potential of ascites. We show that the addition of AAFs to the culture media of EOC cell lines has the potential to induce resistance to standard-of-care drugs (SCDs). We also show that AAFs induce time- and concentration-dependent activation of downstream signalling to signal transducer and activator of transcription 3 (STAT3), and concomitantly altered phosphorylation of mitogen-activated protein kinase kinase (MEK), phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) and nuclear factor NF-kappa-B (NFκB). Antibodies targeting the interleukin-6 receptor (IL6R) effectively blocked phosphorylation of STAT3 and STAT1. Treatments with SCDs were effective in reducing cell viability in only a third of 30 clinically relevant conditions examined, defined as combinations of drugs, different cell lines and AAFs. Combinations of SCDs and novel therapeutics such as trametinib, fludarabine or rapamycin were superior in another third. Notably, we could nominate effective treatment combinations in almost all conditions except in 4 out of 30 conditions, in which trametinib or fludarabine showed higher efficacy alone. Taken together, our study underscores the importance of the molecular characterisation of individual patients' AAFs and the impact on treatment resistance as providing clinically meaningful information for future precision treatment approaches in EOC.

Resting Heart Rate Variability is Independently Associated with Visceral Fat Rating Scores in Saudi Adult Males.

Visceral adipose tissue (VAT) may be a specific modifiable contributor to body composition-related autonomic impairment. To compare heart rate variability (HRV) between groups stratified by visceral fat rating (VFR) and compare associations between HRV and body composition metrics. A cross-sectional study was conducted on healthy men (n=99,age=37.8±13.4 years, body mass index [BMI]=26.9±4.6 kg/m2). HRV was derived from 5-minute electrocardiographic recordings. Body composition (body fat percentage, VFR, and muscle mass to visceral fat ratio [MMVFR]) was estimated using tetrapolar bioelectrical impedance analysis. Participants were categorized into groups according to VFR: G1 (VFR=1-8); G2(VFR=9-12); and G3(VFR>12). Age-adjusted comparisons were made between groups. Independent associations were quantified with multiple linear regressions. P <0.05 was significant. Root-mean square of successive differences (RMSSD) and standard deviation of normal RR intervals (SDNN) were higher for G1 vs. G2 and G3 (p<0.05). Low-frequency power (LF) was higher in G1 than in G2 (p<0.05). VFR and MMVFR were negatively associated with SDNN, RMSSD, LF, and HF (p<0.05). After adjusting for age, BMI, and systolic and diastolic blood pressure, VFR was significantly predictive of RMSSD, SDNN, and HF (p=0.002,-0.027), and MMVFR was significantly predictive of RMSSD and SDNN (p=0.020,-0.023). Men in the lowest VFR category had the highest HRV. VFR was more strongly associated with HRV than body fat percentage and MMVR. Time domain parameters were more sensitive to VAT than frequency domain parameters. HRV parameters could be the primary parameters of interest in tracking cardiac-autonomic status in response to interventions targeting VAT reduction.

The inflammatory markers and locoregional pathological results both have an impact on the prognosis of oral squamous cell carcinoma in patients who have undergone neck dissection

BackgroundLocoregional surgical pathology, with surgical margins at the primary site and lymph node (LN) metastasis, particularly extranodal extension (ENE), plays an important role in the prognosis of oral squamous cell carcinoma (OSCC). In addition, systemic inflammatory response and nutritional status are associated with poor prognosis. PurposeThis study aimed to comprehensively assess the effect of inflammatory markers and locoregional factors on the prognosis of patients with OSCC who underwent neck dissection (ND). MethodsThis retrospective cohort study included patients who had undergone ND for OSCC between 2013 and 2021. The primary predictive variables were the weighted lymph node ratio (WLNR) and inflammatory markers. Primary outcome variables were overall survival (OS) and disease-free survival (DFS). ResultsAmong 153 patients (99 males, 54 females), 55 (35.9 %) had LN metastasis and 11 (7.2 %) exhibited ENE. The inflammatory markers lymphocyte/monocyte ratio (LMR), monocyte/albumin ratio (MAR), C-reactive protein/albumin ratio (CAR), and WLNR demonstrated significant cut-off values for survival, with values of 4.805, 104.72, 0.041, and 0.0235, respectively. The Cox proportional hazards model revealed significant differences in age, WLNR, LMR, MAR, CAR, and vascular, lymphatic, and perineural invasion (Pn). Multivariate analysis indicated that the hazard ratios (95 % confidence intervals) for WLNR (3.416; 1.542–7.566), MAR (2.404; 1.254–4.607), and Pn (2.516; 1.291–4.905) were independent variables for OS. ConclusionsIn patients with OSCC who underwent ND, the inflammatory marker MAR and locoregional factors WLNR and Pn were simultaneously identified as prognostic factors.

Immunophenotyping of Peripheral Blood Cells in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib.

Chronic lymphocytic leukemia (CLL) is a B-cell-derived hematologic malignancy whose progression depends on active B-cell receptor (BCR) signaling. Despite the spectacular efficacy of Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), resistance can develop in CLL patients, and alternative therapeutic strategies are therefore required. Cancer immunotherapy has revolutionized cancer care and may be an attractive approach in this context. We speculated that characterizing the immune responses of CLL patients may highlight putative immunotherapeutic targets. Here, we used high-dimensional spectral flow cytometry to compare the distribution and phenotype of non-B-cell immune populations in the circulating blood of CLL patients treated with Ibrutinib displaying a complete response or secondary progression. Although no drastic changes were observed in the composition of their immune subsets, the Ibrutinib-resistant group showed increased cycling of CD8+ T cells, leading to their overabundance at the expense of dendritic cells. In addition, the expression of 11 different surface checkpoints was similar regardless of response status. Together, this suggests that CLL relapse upon Ibrutinib treatment may not lead to major alterations in the peripheral immune response.

Macrophage energy metabolism in cardiometabolic disease.

In a rapidly expanding body of literature, the major role of energy metabolism in determining the response and polarization status of macrophages has been examined, and it is currently a very active area of research. The metabolic flux through different metabolic pathways in the macrophage is interconnected and complex and could influence the polarization of macrophages. Earlier studies suggested glucose flux through cytosolic glycolysis is a prerequisite to trigger the pro-inflammatory phenotypes of macrophages while proposing that fatty acid oxidation is essential to support anti-inflammatory responses by macrophages. However, recent studies have shown that this understanding is oversimplified and that the metabolic control of macrophage polarization is highly complex and not fully defined yet. In this review, we systematically reviewed and summarized the literature regarding the role of energy metabolism in controlling macrophage activity and how that might be altered in cardiometabolic diseases, namely heart failure, obesity, and diabetes. We critically appraised the experimental studies and methodologies in the published studies. We also highlighted the challenging concepts in macrophage metabolism and identified several research questions yet to be addressed in future investigations.

Markers in Identifying Pathological Complete Response Status in Muscle Invasive Bladder Cancer Patients Who Achieved Clinical Complete Response After Neoadjuvant Chemotherapy

BackgroundPrior research has demonstrated a discrepancy between pathologic and clinical staging in individuals with muscle-invasive bladder cancer (MIBC) following neoadjuvant chemotherapy (NAC). These findings were the major reasons for the under-usage of the bladder preservation strategy. Hence, we aim to explore the reliable markers in identifying pathological complete response (ypCR) status in MIBC patients who achieved clinical complete response (cCR) after NAC. MethodsBetween January 2016 and April 2023, 161 consecutive MIBC patients treated with NAC and achieved cCR were enrolled in the study. Patient clinicopathologic information was documented. Multivariate binary logistic regression was used for determining adjusted odds ratios (OR) and 95% confidence intervals (CI). It considered statistically significant when a P < .05. ResultsOf the 161 MIBC patients with cCR after NAC, 64.0% (103/161) achieved ypCR after RC. The independent factors for ypCR status were the origin of MIBC (secondary vs. Primary) with odds ratios (OR) of 0.433 (P = .027), the pathological type (pure vs. mixed) with OR of 3.556 (P = .003), concurrent carcinoma in situ (yes vs. no) with OR of 0.360 (P = .016), and lymphovascular invasion (yes vs. no) with OR of 0.271 (P = .007). ConclusionThis study demonstrated that primary MIBC, pure UC pathological type, absence of concurrent CIS, and LVI were significant predictors of ypCR in MIBC patients who achieved cCR after NAC and before surgery. These findings may contribute to the decision-making process of bladder preservation strategy in selected patients.

Correlation between plasma ccfDNA, mtDNA changes, CTCs, and epithelial-mesenchymal transition in breast cancer patients undergoing NACT.

Breast cancer is the most prevalent cancer in women, emphasizing need for noninvasive blood biomarkers to aid in treatment selection. Previous studies have demonstrated elevated levels of plasma circulating cell-free DNA (ccfDNA) in breast cancer patients. Both ccfDNA and mitochondrial DNA (mtDNA) are fragments released into the bloodstream. In this study, we investigated effectiveness of ccfDNA and mtDNA as indicators of treatment response and explored their potential as monitoring biomarkers. Additionally, we compared these markers with circulating tumor cell (CTC) data and assessed their relationship with epithelial-mesenchymal transition (EMT). Thirty-six female breast cancer patients and 21 healthy females were included in the study. Quantitative polymerase chain reaction (qPCR) was performed on plasma samples to measure levels of ND1, ND4, ALU115, ALU247, and GAPDH, and DNA integrity was determined by calculating ratios of ALU247/ALU115 and ND4/ND1. After treatment, patients had a significant decrease in ccfDNA levels and a significant increase in mtDNA copy number (mtDNAcn). However, there was no significant change in ccfDNA and mtDNA integrity. When comparing all groups, patients exhibited higher levels of ALU115 and ALU247 compared to controls. Moreover, patients demonstrated significantly lower ccfDNA integrity than controls. This study represents the first comprehensive investigation of plasma ccfDNA levels, mtDNAcn, and integrities collectively. Furthermore, it is the first study to explore the relationship between these markers and CTCs, cancer stem cell markers, treatment response, and metastatic status. Our findings suggest that plasma ccfDNA and mtDNA may serve as potential biomarkers for assessing chemotherapy response and can be employed alone or in combination with other biomarkers to monitor treatment efficacy in breast cancer patients.

The C-reactive protein-albumin-lymphocyte (CALLY) index is a useful predictor of postoperative complications in patients with a colonic stent for obstructive colorectal cancer: a Japanese multicenter study.

The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel score that offers a good reflection of nutritional status, inflammatory response, and immune system status. The CALLY index is reported to correlate with the prognosis of various carcinomas. The purpose of the present study was to investigate the association between the CALLY index and the short-term prognosis of obstructive colorectal cancer managed with a colonic stent. The subjects of this retrospective study were 263 patients who underwent colorectal resection after colonic stenting for obstructive colorectal cancer between 2016 and 2023. Patients were classified into a group with a low CALLY index (CALLY-L group, n = 85) and a group with a high (CALLY-H group, n = 178) CALLY index. The CALLY-L group had greater blood loss (53mL vs 20mL, p = 0.002) and higher poor performance status (PS3; 20% vs 10.1%, p = 0.033), open surgery (21.2% vs 7.3%, p = 0.001), distant metastases (41.2% vs 20.8%, p = 0.01), and postoperative complications (30.6% vs. 18.5%, p = 0.039) than the CALLY-H group. Multivariate analysis identified a prolonged operative time (odds ratio 1.983, 95% confidence interval 1.013-3.881; p = 0.045), greater blood loss (odds ratio 2.572, 95% confidence interval 1.291-5.129; p = 0.007) and a low CALLY index (odds ratio 1.961, 95% confidence interval 1.013-3.795; p = 0.045) as independent predictors of complications. The CALLY index may be a useful predictor of postoperative complications of obstructive colorectal cancer.

End Point Surrogacy in First-Line Chronic Lymphocytic Leukemia.

Surrogate end points are commonly used to estimate treatment efficacy in clinical studies of chronic lymphocytic leukemia (CLL). This patient- and trial-level analysis describes the correlation between progression-free survival (PFS) and minimal residual disease (MRD) with overall survival (OS) in first-line trials for CLL. First, patient-level correlation was confirmed using source data from 12 frontline German CLL Study Group (GCLLSG)-trials. Additionally, a joint-frailty copula model was fitted to validate correlation in the setting of targeted therapies (TT). Second, a meta-analysis of first-line phase III trials in CLL from 2008 to 2024 was performed. Treatment effect correlation was quantified from seven GCLLSG and nine published trials, using hazard ratios (HRs) for time-to-event and odds ratios for binary end points. The GCLLSG analysis set comprised 4,237 patients. Patient-level correlation for PFS/OS was strong with Spearman Rho >0.9. The joint-frailty copula indicated a weak correlation for chemotherapy/chemoimmunotherapy (C/CIT) with a tau of 0.52 (95% CI, 0.49 to 0.55) while the correlation was strong for TT (tau, 0.91 [95% CI, 0.89 to 0.93). The meta-analysis set contained a total of 8,065 patients including 5,198 (64%) patients treated with C/CIT and 2,867 (36%) treated with TT. Treatment-effect correlation of the HRs for PFS and OS was R = 0.75 (95% CI, 0.74 to 0.76, R2 = 0.56) while correlation of end-of-treatment MRD with PFS and OS was R = 0.88 (95% CI, -0.87 to 0.89; R2 = 0.78) and 0.71 (95% CI, 0.69 to 0.73; R2 = 0.5), respectively. Patient-level correlation was confirmed in the setting of TTs while treatment-effect correlation between PFS and OS remains uncertain. MRD response status showed a high treatment-effect correlation with PFS but not OS, with the caveat of a limited number of randomized trials with available MRD data.

Ascorbic acid-mediated enhancement of antioxidants and photosynthetic efficiency: A strategy for enhancing canola yield under salt stress

Ascorbic acid (AsA), a water-soluble antioxidant, act as cofactor for enzymes that regulate photosynthesis, hormonal and antioxidant biosynthesis that enables the plants to alleviate the harmful effects of salinity stress. The study was aimed to investigate the ameliorative role of foliar application of 200 ppm ascorbic acid (AsA) in improving growth by changing antioxidant response, photosynthetic capacity and mineral nutrient status of two canola varieties (Dunkled and Cyclone) under salinity stress (200 mM NaCl). Salt stress reduced plant biomass, photosynthetic activity, and accumulation of macro and micronutrients such as K+, Ca2+and Zn2+ in both canola varieties, on the other hand accumulation of Na+ and Cl−was increased. The salinity-induced oxidative stress (H2O2 and MDA) caused photoinhibition of PSII at the donor and acceptor ends. The salinity-induced reduction in efficiency of electron donation to PSII (Fv/Fo) and electron transport through PSII (Fm/Fo), especially in Cyclone, significantly reduced ETRII thus enhancing CEF around PSI and NPQ in both canola varieties that has been considered as photo-protective mechanism of plants. In addition, salt stress enhanced CEF around PSI. However, application of AsA improved the structural stability of PSII, linear electron transport and reduced donor end limitation of PSI activity by improving electron transfer from PSII to PSI. The application of AsA improved the stomatal conductance, inter-cellular CO2 concentration and net CO2 assimilation rate thereby resulting in improved consumption of extra-electrons in CO2 fixation generated by photosynthetic electron transport. Exogenous AsA application reduced the oxidative stress and improved the antioxidant potential by managing extra-electrons produced in CO2 fixation. All these physiological and biochemical changes due to AsA application helped the canola plants to improve growth and yield under salinity. Thus, the application of ascorbic acid has the potential to ameliorate the detrimental effects of NaCl stress on canola plants.

Comparing DAPSA, DAPSA28, and DAS28-CRP in Patients With Psoriatic Arthritis Initiating a First Tumor Necrosis Factor Inhibitor Across Nine European Countries.

Because 66/68 joint counts are not always performed in routine care, we aimed to determine which of the modified 28-joint disease activity index for psoriatic arthritis (DAPSA28) or 28-joint disease activity score with C-reactive protein (DAS28-CRP) should be preferred for monitoring disease activity in psoriatic arthritis (PsA) when the original DAPSA (66/68 joints) is not available. Prospectively collected real-world data of European bionaive patients with PsA initiating a first tumor necrosis factor inhibitor were pooled. Remission and response status were evaluated at 6 months by remission (DAPSA ≤ 4, DAPSA28 ≤ 4, and DAS28-CRP < 2.6), response (75% improvement for DAPSA and DAPSA28), and combined EULAR good/moderate responses for DAS28-CRP. Logistic regression analyses on multiple imputed data were used to identify baseline predictors. Remission and response cohorts included 3,159 and 1,866 patients, respectively. The 6-month proportions achieving remission/response were DAPSA (27%/44%), DAPSA28 (28%/44%), and DAS28-CRP (59%/80%). Of 14 possible baseline predictors, 11 predicted both DAPSA and DAPSA28 remission (8 of which also predicted their response, indicated by "*"): longer disease duration*, male sex*, and higher CRP* were positive, whereas older age*, higher body mass index*, patient fatigue*, and global, physician global, health assessment questionnaire score*, and tender and swollen* joint counts were negative predictors. Eight and five of these predicted DAS28-CRP remission and response, respectively. In patients with PsA, DAPSA28 should be preferred over DAS28-CRP as a substitute for DAPSA when 66/68 joint counts are not available because of the large overlap in remission and response status and in predictors between DAPSA and DAPSA28.

Productive Performance, Stress Response, and Immune Status of Nursery Pigs Fed a Diet Containing Hemp Seed Meal

This study aimed to examine hemp seed meal (HSM) in the nursery pig diet for productive performance, stress response, and immune status. Forty castrated [(Landrace × Large White) × Duroc] pigs, 3 weeks of age with an initial body weight of 5.48±0.2 kg were used in this study. The pigs were divided into four groups with 10 replicates per group. The experiment design was a completely randomized design. The dietary treatments were the control group fed the basal diet without HSM (HSM0) and the groups fed diet contained 5, 10 and 15% HSM (HSM5, HSM10 and HSM15), respectively. The results showed that HSM had significant nutritional value with crude fat, crude protein, crude fiber, and lysine of 7.95, 32.46, 12.94 and 1.49%, respectively. In addition, it had gross energy of 3,594 kcal/kg. The use of HSM in the nursery pig diet showed that the average daily feed intake during weeks 1-2 of the pigs in the HSM10 group was better than the HSM15 (p&lt;0.05) group. Additionally, their bodyweight gain and average daily gain throughout the trial were greater than other groups (P&lt;0.05). There were no significant differences (P&gt;0.05) in the feed conversion ratio (FCR) between the experimental groups. The stress conditions caused by oxidative reactions were observed by the level of enzymes in the plasma of the pigs. The lowest concentration of superoxide dismutase (SOD) and the highest of glutathione peroxidase (GPx) (P&lt;0.05) were found in HSM15 group. The HSM5 group had the minimum cortisol hormone levels (P&lt;0.05), which were not statistically different from the HSM10 group. It was also found that the HSM10 group had the highest immunoglobulin M (IgM) concentration (P&lt; 0.05), while the pig in groups HSM10 and HSM15 had the highest immunoglobulins G (IgG) concentrations (P&lt;0.05). In conclusion, the use of HSM at 10% level in the diet was the most efficiency for nursery pigs.

Impact of campus closure during COVID-19 on lifestyle, educational performance, and anxiety levels of college students in China

BackgroundHigher education students exhibit heightened sensitivity to environmental changes as they navigate the critical transition from adolescence to adulthood. The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to universities worldwide, exemplifying a crisis that profoundly affects the learning outcomes and psychological status of college students. Although it is known that campus lockdown has triggered dramatic changes in lifestyles, learning outcomes, and psychological statuses, in-depth knowledge of the causal relationships among these changes remains largely unclear.MethodsHere, we conducted a cross-sectional survey designed to assess the impact of campus closure during COVID-19 on lifestyle, educational performance, and anxiety levels among college students. We surveyed over 3,500 junior college, undergraduate and graduate participants from 94 colleges/universities across 30 provinces, municipalities, and autonomous regions in China.We employed structural equation modeling (SEM) to explore the relationships between changes in lifestyle, educational performance, and levels of anxiety associated with campus open or closure regulations during the COVID-19 pandemic.ResultsOur results discovered that sleep duration, physical activity involvement, and social connections were crucial for sustaining students' learning outcomes and mental health. The shift to online learning and campus lockdown exacerbated stressors, contributing to heightened anxiety (β = 0.066), disrupted sleep patterns, and enhanced physical activity (β = 0.070) and reduced learning effect (β = -0.059). Sleep patterns were disrupted by the campus lockdown, an effect mediated by the degradation of relationships among classmates. Nonetheless, the best-fitting SEM uncovered the intricate relationships among lifestyle changes, learning outcomes, and psychological status in response to sudden environmental changes (Fisher’s C = 80.949, P = 0.328). These results highlight the critical role of adaptable, supportive campus policies tailored to meet the diverse needs and interests of students during and beyond crises (Fisher’s C = 59.568, P = 0.809).ConclusionsOur study advocates for a holistic approach that addresses the multifaceted aspects of student life to cultivate a resilient academic community. This approach contributes to a deeper understanding of the effects of sudden environmental changes on students' psychological well-being and academic performance in the post-pandemic era.

Abscopal effect in a patient with advanced hepatocellular carcinoma upon resuming bevacizumab in combination with atezolizumab after radiotherapy.

Combining bevacizumab with atezolizumab enhances the antitumor effects of the treatment by activating an immune response. This combination is approved for the treatment of unresectable hepatocellular carcinoma (HCC). An abscopal effect is associated with an immune response triggered by radiation-induced immunogenic cell death, based on experimental models. Thus, combining radiotherapy and immunotherapy is expected to induce an abscopal effect. However, the clinical significance of immunotherapy in the abscopal effect remains unknown due to the rarity of clinical cases. Herein, we report a case of advanced HCC with lung and adrenal metastases. The antitumor efficacy of atezolizumab and bevacizumab (atezo/bev) was enhanced following stereotactic body radiotherapy (SBRT), although atezo/bev did not yield a sufficient therapeutic response pre-SBRT. Furthermore, an abscopal effect following SBRT was not observed during atezolizumab alone but was evoked after resuming bevacizumab in combination with atezolizumab, culminating in the patient achieving a complete response status. These findings suggest that immune activation following radiotherapy may be related to the induction of an abscopal effect in clinical practice as well as in experimental settings, and combining immunotherapy with bevacizumab post-radiotherapy could evoke an abscopal effect in a case of HCC, even though immune checkpoint inhibitor use alone may be insufficient.

Responses of oscar (Astronotus ocellatus) to different temperatures and its interaction with early mild stress

Non-optimum temperature results in stress in fish through different biological and physiological processes. This study investigated how early mild stress (EMS) and temperature can influence growth, hematology, blood biochemistry, immunological response, antioxidant system, liver enzymes, and stress response of juvenile oscar (Astronotus ocellatus; 8.02 ± 0.81 g) before and after acute confinement stress (AC stress). Eight experimental treatments were 17D (farmed at 17 °C), 22D (farmed at 22 °C), 27D (farmed at 27 °C), 32D (farmed at 32 °C), 17DES (farmed at 17 °C and EMS), 22DES (farmed at 22 °C and EMS), 27DES (farmed at 27 °C and EMS), and 32DES (farmed at 32 °C and EMS). At the end of the experiment (nine weeks), there was no significant difference in survival rate, feed conversion ratio, body composition, and survival rate after the AC stress (ten weeks). The growth rates in the 17 and 32 °C groups were lower than others, showing the negative effect of temperature being too high or too low. After nine weeks, fish farmed at 32 °C had the highest hematological parameters (hematocrit, hemoglobin, red blood cells, and blood performance) and liver enzymes (lactate dehydrogenase, alanine transaminase, and aspartate transaminase). This group also has the lowest lysozyme, alternative complement pathway (ACH50), immunoglobulin, complement C3, complement C4, superoxide dismutase, and glutathione peroxidase. The EMS did not positively or negatively affect fish physiology in this study. In conclusion, the optimum temperature for oscar to achieve the best growth performance, immune response, and health status is 22–27 °C.

Elevated allostatic load is associated with poorer response to repetitive transcranial magnetic stimulation in treatment-resistant depression

This cohort study investigated whether allostatic load (AL) is associated with treatment response to repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD). Pre-treatment blood samples measured AL across multiple systems. Pre- and post-treatment mood changes were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Associations between AL and treatment outcomes were explored. Higher pre-treatment AL was significantly associated with poorer post-treatment response status but was not significantly associated with smaller reduction in MADRS score after 4 weeks of treatment. Identifying biomarker profiles informed by the AL model could enhance treatment decisions in TRD, reducing risks associated with prolonged, ineffective rTMS trials and emphasizing the need for reliable predictive biomarkers.