Stage Group Research Articles

Supplementation with inulin reverses cognitive flexibility alterations and modulates the gut microbiota in high-fat-fed mice

IntroductionAlterations in cognitive performance are associated with inadequate nutritional states and diet composition. Prebiotics, such as inulin, are substances that can modulate the gut microbiome and, consequently, brain function by producing metabolites such as short-chain fatty acids (SCFAs). This study aimed to evaluate the effect of supplementation with inulin on cognitive flexibility, body composition, and gut microbiota in a murine model exposed to a high-fat (HF) diet.MethodsCD1 mice were divided into five groups: control fed a standard diet (C), high-fat diet (HF), inulin (I), high-fat diet with inulin (HFI), and manipulation control (M). Dietary supplementation was administered for 6 weeks. Cognitive flexibility was assessed using the Attentional Set-Shifting Test (AST). In addition, body composition was measured via electrical bioimpedance and adipose tissue compartments of each mouse were removed and weighed. Finally, gut microbiota metataxonomic was analyzed through metataxonomic bacterial 16S rRNA sequencing.ResultsWe observed that HF group required more AST trials than the C, HFI, and I groups in the compound discrimination (CD) and extra-dimensional (ED) stages. Notably, the HFI group required fewer trials than the HF group in the ED stage (p = 0.0187). No significant differences in overall body composition were observed between the groups. However, the percentage of gonadal and peritoneal adipose tissue was significantly higher in the HF and I groups compared to the C group. Statistically significant differences in alpha diversity for gut microbiota were observed using the Shannon, Simpson, and Chao1 indices. The I group showed a decrease in bacterial diversity compared to the HF group. While no differences were observed between groups in the phyla Bacillota and Bacteroidotes, Clostridium bacteria represented a lower proportion of sequences in the I group compared to the C group. Additionally, Lactobacillus represented a lower proportion of sequences in the HF group compared to the C and I groups.DiscussionThese findings suggest that supplementation with inulin could be a useful approach to mitigate the negative effects of an HF diet on cognitive flexibility and modulate gut microbiota composition.

A review of early small bowel obstructions in staged IPAA procedures.

Small bowel obstructions (SBOs) are a common complication following staged IPAA. Our goal was to compare early post-operative SBO outcomes between different staged ileal pouch-anal anastomosis (IPAA) and to further analyze the type of procedures required in patients who needed operative management of SBO. In this retrospective cohort study, we selected all patients who presented to our tertiary care center between 2008 and 2017, with ulcerative colitis or IBD-Unspecified colitis and who underwent a primary total proctocolectomy with IPAA for medically refractory disease or dysplasia (n = 623). Patients were divided into 4 groups based on staged IPAA received (1 stage vs 2 stage vs modified 2 stage vs 3 stage). Primary outcomes were compared between both groups using univariate analysis and included SBO within 6months post-operatively of one of the IPAA stages or 18months since the first surgery for patients who underwent 1 or 2 stage IPAAs, and need for readmission and reoperation. Risk factors for SBO, reoperation and readmission due to SBO were evaluated using multivariate logistic regression. Stage 2 and 3 patients had the highest rates of SBO post-operatively. There was a significant difference in the rate of readmission between groups, with 2 and 3 stage groups having the highest rates (p < 0.05) but the rate of SBO and reoperations was not significantly different between groups. Of all patients with an SBO, 34% required operative intervention. Of these, 65% underwent diagnostic laparoscopy with lysis of adhesions and 27% required an open procedure. Small bowel obstructions are a common complication of staged IPAA procedures. Patients who underwent 2 and 3 stage IPAA had the highest rates of SBO, although not statistically significant. A third of patients with an SBO required surgical intervention, with diagnostic laparoscopy and lysis of adhesions being the most common procedure.

Treatment of kidney disease: an analytical decision model at a Swiss university hospital

Abstract Background An observational hospital-based cohort study, where the kidney disease staging is identified as a digital marker, and the association between the standardised staging of Kidney Disease (KD) and the outcomes is assessed along the treatment process. Methods The clinical and administrative data for all patients are stored in the Clinical Data Warehouse. A specific digital marker for an exact KD staging is applied. Three retrospective patient cohorts for exact and imprecise staging and missing diagnosis are defined and compared regarding the in-hospital mortality, all-cause mortality and disease progression. Results In total, 83146 hospitalisations of 40421 patients with KD, treated in 2014-2023 (2016-2023 will be updated) were identified; the number of the first hospitalisations with exact staging was 847 (2%), unprecise 29934 (72%) and missing diagnosis (26%). The demographic and baseline factors distribution between groups was tested with no association (chi-squared test statistic). The median survival time with a 95% CI was 7.94 (7.66, 8.81) years for the exact and 7.47 (7.42, 7.53) for the imprecise staging group. A log-rank and loglikelihood tests indicated a significant difference in survival between the groups, p &amp;lt; 0.0001. The Cox regression model shows a statistically significant difference in Hazard Ratio; KD staging, age, Elixhauser van Walraven index, treatment, nephrotoxic medication, contrast agent application, and AKI were identified as the significant covariates, C-statistic 0.730, Likelihood ratio test, Wald test, log-rank score on 42 df, p &amp;lt; 2e-16. ANOVA analysis confirmed a significant difference in cost distribution between the groups. An economic decision model proposal integrates the findings, combining a profile-level Markov cohort with a Discreet Time-To-Event Simulation DICE. Conclusions The study demonstrates a better outcome regarding all-cause mortality, in-hospital mortality, and costs if a standardised KD staging was applied. Key messages • Intuition (clinical judgement) and standardised kidney disease staging perform differently regarding clinical outcomes and costs. • The study demonstrates a better outcome regarding all-cause mortality, in-hospital mortality, and costs if a standardised KD staging was applied.

Analysis of changes in lower limb joints of athletes during the movement of wild horses’ mane parting based on biomechanics

In the era of fitness, more and more young people are familiar with Taijiquan, a kind of physical fitness exercise. By conducting biomechanical analyses of the movements of Taijiquan, it is possible to exercise the body better. Numerous techniques in Taijiquan make it difficult to study each individually. Therefore, this paper studied the movement of “wild horses’ mane parting” in terms of biomechanics by analyzing the joint angle, stiffness, and impulse during this movement. Twenty male athletes were selected as subjects and divided into a professional group and a beginner group according to their training periods. High-speed cameras were used to shoot the “wild horses’ mane parting” movement. The angles of lower limb joints in these athletes were measured to calculate joint impulse and stiffness. The results showed that, compared with the professional group, there were significant differences in the adduction and abduction angle and the internal and external rotation angle between the beginner group and the professional group in the single-leg support movement stage (P&lt; 0.05). There were also significant differences in joint impulse and stiffness (P&lt; 0.05). Compared with beginners, long-term professional practitioners can make their movements more standardized. By comparing movements and data analysis, beginners can make their movements more standardized when practicing Taijiquan and avoid the risk of sports injury. The novelty of this article lies in the use of high-speed cameras to capture athletes’ movements, enabling accurate analyses of their joints and providing effective references for precise training.

HOXA9 and CD163 potentiate pancreatic ductal adenocarcinoma progression

BackgroundThe role of HOXA9 requires investigations in pancreatic ductal adenocarcinoma (PDAC) as HOXA9 inhibitors are being developed. HOXA9 might attract CD163 expressed tumor associated macrophages (TAM) and could affect PDAC prognosis. This work aims to study the expression and relevance of HOXA9 and CD163 in PDAC progression.Materials and methodsSelected 98 PDAC and 98 adjacent non tumor tissues as a control group were immunostained with HOXA9 and CD163 antibodies.ResultsPDAC displayed highly significant higher HOXA9 staining intensity, percent and H score values than control group. HOXA9 staining of PDAC cases showed significant associations with poor prognostic indicators including larger tumor size, higher grade and advanced stage. PDAC showed highly significant differences regarding CD163 macrophage-specific staining intensity, percent and H score values than control group. CD163 showed significant higher expressions with larger tumor size, higher histological grade and advanced stage group. HOXA9 staining in PDAC showed highly significant direct correlations with CD163 positive macrophages. Follow up of PDAC cases revealed that high median H score of HOXA9 and CD163 were significantly associated with worse overall survival. CD163 was an independent prognostic marker of worse survival.ConclusionsIn conclusion, HOXA9 could potentiate PDAC progression by stimulating CD163 expressed TAM attraction in tumors. HOXA9 and CD163 could participate in PDAC therapy. HOXA9 and CD163 could be predictors of worse prognosis and shorter survival in PDAC.

Construction of mitochondrial quality regulation genes-related prognostic model based on bulk-RNA-seq analysis in multiple myeloma.

Mitochondrial quality regulation plays an important role in affecting the treatment sensitivity of multiple myeloma (MM). We aimed to develop a mitochondrial quality regulation genes (MQRGs)-related prognostic model for MM patients. The Genomic Data Commons-MM of bulk RNA-seq, mutation, and single-cell RNA-seq (scRNA-seq) dataset were downloaded, and the MQRGs gene set was collected previous study. "maftools" and CIBERSORT were used for mutation and immune-infiltration analysis. Subsequently, the "ConsensusClusterPlus" was used to perform the unsupervised clustering analysis, "survminer" and "ssGSEA" R package was used for the Kaplan-Meier survival and enrichment analysis, "limma" R, univariate and Least Absolute Shrinkage and Selection Operator Cox were used for RiskScore model. The "timeROC" R package was used for Receiver Operating Characteristic Curve analysis. Finally, the "Seurat" R package was used for scRNA-seq analysis. These MQRGs are mainly located on chromosome-1,2,3,7, and 22 and had significant expression differences among age, gender, and stage groups, in which PPARGC1A and PPARG are the high mutation genes. Most MQRGs expression are closely associated with the plasma cells infiltration and can divide the patients into 2 different prognostic clusters (C1, C2). Then, 8 risk models were screened from 60 DEGs for RiskScore, which is an independent prognostic factor and effectively divided the patients into high and low risk groups with significant difference of immune checkpoint expression. Nomogram containing RiskScore can accurately predict patient prognosis, and a series of specific transcription factor PRDM1 and IRF1 were identified. We described the based molecular features and developed a high effective MQRGs-related prognostic model in MM.

Combination of intravoxel incoherent motion histogram parameters and clinical characteristics for predicting response to neoadjuvant chemoradiation in patients with locally advanced rectal cancer.

To explore the value of histogram parameters derived from intravoxel incoherent motion (IVIM) for predicting response to neoadjuvant chemoradiation (nCRT) in patients with locally advanced rectal cancer (LARC). A total of 112 patients diagnosed with LARC who underwent IVIM-DWI prior to nCRT were enrolled in this study. The true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and microvascular volume fraction (f) calculated from IVIM were recorded along with the histogram parameters. The patients were classified into the pathological complete response (pCR) group and the non-pCR group according to the tumor regression grade (TRG) system. Additionally, the patients were divided into low T stage (yp T0-2) and high T stage (ypT3-4) according to the pathologic T stage (ypT stage). Univariate logistic regression analysis was implemented to identify independent risk factors, including both clinical characteristics and IVIM histogram parameters. Subsequently, models for Clinical, Histogram, and Combined Clinical and Histogram were constructed using multivariable binary logistic regression analysis for the purpose of predicting pCR. The area under the receiver operating characteristic (ROC) curve (AUCs) was employed to evaluate the diagnostic performance of the three models. The values of D_ kurtosis, f_mean, and f_ median were significantly higher in the pCR group compared with the non-pCR group (all P < 0.05). The value of D*_ entropy was significantly lower in the pCR group compared with the non-pCR group (P < 0.05). The values of D_ kurtosis, f_mean, and f_ median were significantly higher in the low T stage group compared with the high T stage group (all P < 0.05). The value of D*_ entropy was significantly lower in the low T stage group compared with the high T stage group (P < 0.05). The ROC curves indicated that the Combined Clinical and Histogram model exhibited the best diagnostic performance in predicting the pCR patients with AUCs, sensitivity, specificity, and accuracy of 0.916, 83.33%, 85.23%, and 84.82%. The histogram parameters derived from IVIM have the potential to identify patients who have achieved pCR. Moreover, the combination of IVIM histogram parameters and clinical characteristics enhanced the diagnostic performance of IVIM histogram parameters.

Ninth Version of the AJCC and UICC Nasopharyngeal Cancer TNM Staging Classification

Accurate staging is a fundamental step in treating patients with nasopharyngeal carcinoma (NPC) worldwide; this is crucial not only for prognostication, but also for guiding treatment decisions. The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) system is the global language for clinicians, researchers, and cancer registries. Continual improvement that aligns with contemporary pattern of care is essential. To improve the prognostic accuracy and clinical applicability of the eighth edition (TNM-8) for NPC. This multicenter study analyzed patients with NPC with detailed tumor features during January 2014 and December 2015 and was reviewed by experienced radiologists. The data analysis was completed in December 2023. The findings were further confirmed with internal and external validation. Statistical analyses and clinical considerations were reviewed by the AJCC/UICC multidisciplinary head and neck panels and attained consensus. The recommendations were evaluated by the AJCC Evidence-Based Medicine Committee before final endorsement as the ninth version (TNM-9). The primary end point was overall survival. Adjusted hazard ratios of different subgroups were then assessed for confirmation of optimal stage grouping. Of the 4914 patients analyzed, 1264 (25.7%) were female and 3650 (74.3%) were male; the median (SD) age was 48.1 (12.0) years. Advanced radiological extranodal extension (with involvement of adjacent muscles, skin, and/or neurovascular bundles) was identified as an independent adverse factor for all end points: this was added as a criterion for N3. Patients with nonmetastatic disease were regrouped into stages I to III instead of TNM-8 stages I to IVA. Significant hazard discrimination was achieved by grouping T1-2N0-1 as stage I, T3/N2 as stage II, and T4/N3 as stage III. Although the T1-2N0-1 subgroups had comparable 5-year overall survival, subdivisions into IA (T1-T2N0) and IB (T1-T2N1) were recommended due to the distinction in adjusted hazard ratios following adjustment for chemotherapy use. Metastatic disease was exclusively classified as stage IV, and prognostication was further refined by subdivision into IVA (M1a, ≤3 lesions) and IVB (M1b, >3 lesions). TNM-9 demonstrated superiority compared with TNM-8 in major statistical aspects. The results of this diagnostic study suggest that the ninth version of TNM staging for NPC, based on robust analyses and a comprehensive review by the AJCC/UICC staging committees, provides an improved staging system for global application and a framework for future incorporation of nonanatomical factors. This will be launched for global application in January 2025.

Impact of Smoking on Overall and Cancer-Specific Mortality in Prostate Cancer: Elevated Risks in Older and Early-Stage Patients—A Population-Based Study

Prostate cancer (PCa) ranks sixth in cancer mortality among Taiwanese men, with smoking rates remaining high despite the 2009 Tobacco Hazards Prevention Act. This study used the Taiwan Cancer Registry to evaluate smoking’s impact on PCa mortality, providing important information for healthcare strategies and patient management. From 2011 to 2017, 23,107 PCa patients were analyzed, with 7164 smokers and 15,943 non-smokers. The baseline characteristics, clinical stages, comorbidities, and treatment modalities were all included to estimate overall and cancer-specific mortality using the Cox regression model and Kaplan–Meier analysis. The stratified analysis of clinical stage and age group was also estimated. Our study found an association between smoking and increased overall and cancer-specific mortality in PCa patients. Although smokers over 60 had higher risks of overall mortality than non-smokers, cancer-specific mortality did not show significant differences in any age group. Smokers had higher overall mortality than non-smokers across all clinical stages, but cancer-specific mortality was significantly raised only in early-stage cases. In conclusion, smoking is associated with higher overall mortality in PCa patients, with a significant increase in cancer-specific mortality in early-stage cases. Therefore, active smoking management is critical for clinical urologists, particularly in the treatment of early-stage patients.

Stimulation of inactivated Metschnikowia bicuspidata promotes the growth, and immunity of Eriocheir sinensis larvae

The Chinese mitten crab (Eriocheir sinensis) is an economically essential crustacean specie in China. The outbreak of disease caused by Metschnikowia bicuspidata has resulted in high mortality and huge economic loss in the E. sinensis aquaculture industry. Immune priming can protect invertebrates against pathogens in the second exposure, which has been reported in adult E. sinensis and provides a novel approach for disease control. This study evaluated the effects of treatment with formalin-killed M. bicuspidata on the growth, development, and immunity of E. sinensis embryos and larvae. Stimulation of E. sinensis embryos with inactivated M. bicuspidata (Mb group) did not significantly affect the mass and size of embryos. While the carapace width, abdominal length, and tail length of larvae in the Mb group were significantly longer than those of control group in most stages. At 120 h and 144 h after embryo hatching, the metamorphosis rate of larvae in the Mb group was 24.59-fold (p < 0.05) and 16.07-fold (p < 0.001) higher than that in the control group. Moreover, after the larvae suffered alive M. bicuspidata challenge, the mortality in the Mb group significantly decreased (0.48-fold, p < 0.05) compared with that in the control group, and the mRNA expression levels of genes related to immunity (MAPK, Toll2, and STAT), growth (ATGL, Chi, Chymotrypsin, and mTOR), and development (Ubx) were significantly increased in the Mb group. These results suggested that stimulation of E. sinensis embryos with inactivated M. bicuspidata significantly promoted the growth and development of larvae and endowed them with stronger resistant capacity to M. bicuspidate. This finding may provide a novel and safe approach for preventing disease and improving larvae quality in E. sinensis aquaculture.

Role of Surgery in Potentially Resectable Small-Cell Lung Cancer Based on the Eighth Edition of the TNM Classification: A Population Study of the US SEER Database.

This study aimed to identify a specific SCLC population that would benefit from surgery. This study utilized patient data retrieved from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. To mitigate clinical biases, the propensity score matching (PSM) technique was employed. Separate cohorts were aligned using PSM according to the AJCC 8th edition TNM classification. The Kaplan-Meier method and a competing risk model were applied to evaluate overall survival (OS) and lung cancer-specific survival (LCSS), respectively. Among the 3394 patients with potentially resectable SCLC included in the study, 3062 underwent chemoradiotherapy and 332 underwent surgical treatment with adjuvant chemotherapy. Surgery was associated with better OS (median OS: 49 months; 95% CI: 35-63 months vs. 27 months; 95% CI: 21-33 months, p < 0.001) and LCSS (SHR, 0.578; 95% CI: 0.411-0.815, p < 0.001) in stage I patients after PSM. However, there was no significant difference in OS and LCSS between the surgery and nonsurgery groups in stage II and III patients after PSM. In the entire cohort, lobectomy was associated with improved OS (median OS: 48.6 vs. 28.7 months, p < 0.0001), but not LCSS (SHR, 0.696; 95% CI: 0.466-1.040, p = 0.078) compared with sublobar resection after PSM. Surgery with adjuvant chemotherapy significantly improved the survival prognosis of patients with early-stage SCLC. However, surgical treatment should be carefully considered in patients with stage II/III disease. Lobectomy is oncologically equal to sublobar resection.

The prognostic value of the 8th American Joint Committee on cancer anatomic and prognostic stage groups for penile cancer: A multicenter collaboration study

ObjectiveThe aim of this study was to investigate the value of 8th American Joint Committee on Cancer (AJCC) anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement. MethodsThe clinical and histopathologic data from 16 centers between 2000 and 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups. Kaplan–Meier plots were used to estimate the disease-specific survival (DSS) of the patients. The accuracy of the staging systems was investigated using the Harrell's concordance index (C-index). ResultsThe 5-year DSS rates for patients with stages 0is/a, I, IIA, IIB, IIIA, IIIB, and IV (stage 0 to stage IV) disease were 100 %, 98.9 %, 85.5 %, 81.1 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.798, pI–IIA<0.001, pIIA–IIB=0.486, pIIB–IIIA<0.001, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). According to the modified model 1 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100 %, 98.9 %, 87.8 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.798, pI–II<0.001, pII–IIIA=0.002, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). Similarly, according to the modified model 2 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100 %, 99.0 %, 85.8 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.757, pI–II<0.001, pII–IIIA=0.008, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). The C-index of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups. These results were confirmed by the bootstrap internal validation. ConclusionThere is still room for improvement about 8th AJCC anatomic and prognostic stage groups. The improved models, which are more concise and convenient, had a similar predictive value.

Para-aortic and pelvic lymphadenectomy in locally advanced cervical cancer with pelvic lymph node metastasis

ObjectiveThis study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis.MethodsA total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups’ progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared.ResultsThe surgical staging group started radiotherapy 10.2 days (range 9–12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively).ConclusionPerforming surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs.Graphical

The Importance of Combination Therapy in a Patient with Advanced Stage Group 1 Pulmonary Arterial Hypertension

The Importance of Combination Therapy in a Patient with Advanced Stage Group 1 Pulmonary Arterial Hypertension

Variation in bovine milk stability according to lactational stage and genetic group.

We address the hypothesis that at early and late lactation milk presents low ethanol stability due to high acidity and ionic calcium values. Our aim was to evaluate the functional traits of milk (milk ethanol stability: MES, acidity and ionic calcium: iCa) according to lactation stage in different genetic groups. Raw milk samples were collected from Jersey (n = 271), Holstein (n = 248) and Jersey × Holstein crossbred cows (n = 82), raised on five commercial farms located in the state of Paraná, Brazil. Milk composition, somatic cell count (SCC), milk urea nitrogen (MUN), MES, pH, acidity and iCa were determined. Days in milk (DIM) were categorized into four classes: 1-60, 61-150, 151-305 and over 305 DIM. Data were submitted to analysis of variance. Fixed and random effects were incorporated into the model, in a repeated measures in time arrangement using the mixed models methodology. Significant interactions between DIM class and genetic groups were detected. The comparison between each combination of genetic group and DIM class showed that at the beginning of lactation, Holsteins produced milk with higher MES than Jersey and crossbreds. At 105-305 DIM Holstein milk presented higher MES than Jersey, while beyond 305 DIM Holstein milk showed higher MES than crossbred cows. At the beginning of lactation acidity was higher in Holstein milk and crossbreds compared with Jersey, while acidity was lower in Holstein milk compared with Jersey and crossbreds in the other lactation stages. Ionic calcium was highest after lactation peak for Holstein, but did not vary between lactation stages for Jersey and crossbreds. Functional characteristics of bovine raw milk such as MES, iCa and acidity varied between lactation stages in a distinct manner according to genetic groups. Early and end lactation stages are challenging in terms of low stability, especially for Jersey and crossbreds.

Did the UEFA Champions League winners start in an easy group?

&lt;p class="MsoNormal" style="margin-top: 12.0pt;"&gt;&lt;span lang="EN-US" style="font-family: 'times new roman', times, serif; font-size: 14pt;"&gt;Competitive balance indicates the degree of control participating teams have over a sports competition. Supporters look for excuses to justify their team&amp;rsquo;s defeat and the triumph of their rivals. If the competition has required a preliminary qualifying group stage, they will argue that the winning team was in an "easy group" from the start, and their team was unlucky to be in a "difficult group". It is therefore of interest to determine what is an "easy group" and what is a "difficult group". This is directly related to the concept of competitive balance. We have a wide range of indices to measure competitive balance. We will use the Distance to Competitive Balance, a standardized index that complies cardinality property. The perfectly unbalanced distribution is the truncated cascade, which allows the maximum value of concentration to be obtained. We focus our attention on the UEFA Champions League, before and after competition, and we measure the competitive balance of the qualifying stage groups between the 1999/2000 and 2022/2023 seasons. The composition of the UEFA Champions League groups seems to be balanced and has no influence on which team will be the champion. A highly competitive group will be more "difficult" in terms of qualifying than a highly concentrated one. Supporters say that their team was unlucky to be in a &amp;ldquo;difficult&amp;rdquo; group, but the data does not prove them right.&lt;/span&gt;&lt;/p&gt;

Impact of Baseline Renal Insufficiency on Piflufolastat F-18 Performance and Investigation of Changes in Renal Function Following Piflufolastat F-18 Administration: Results From the OSPREY Trial

IntroductionPiflufolastat F-18, a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, is predominantly eliminated via urinary excretion, and the kidneys have one of the highest absorbed doses. Therefore, this subgroup analysis aimed to investigate the impact of piflufolastat F-18 on renal function and its diagnostic performance in patients stratified by baseline renal function. Patients and MethodsThe OSPREY clinical trial enrolled 2 cohorts: A—high-risk patients undergoing radical prostatectomy with pelvic lymphadenectomy, and B—patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Baseline estimated glomerular filtration rates were calculated, and patients were stratified by baseline chronic kidney disease (CKD) stage. Changes in serum creatinine within 28 days postdose and diagnostic performance of piflufolastat F-18 were assessed for each CKD stage group in both cohorts. Results385 patients (cohort A, n = 268; cohort B, n = 117) underwent piflufolastat F-18-PET/CT. Baseline and postpiflufolastat F-18 median creatinine levels (mg/dL) were similar for patients in cohort A (0.95 [n = 264] vs. 0.95 [n = 252], respectively) and cohort B (0.93 [n = 116] vs. 0.96 [n = 84], respectively). Among 332 men (cohort A, n = 249; cohort B, n = 83) with baseline and postpiflufolastat creatinine measurements, there were minimal changes in creatinine across all baseline CKD stage groups (median change ranged from -0.02 to 0.023 in groups with >1 patient). The diagnostic performance of piflufolastat F-18 showed no meaningful differences when stratified by baseline CKD stage. ConclusionPiflufolastat F-18 appears to be safe and effective for imaging prostate cancer, including men with mild/moderate renal insufficiency.

In vitro exposure to butylparaben impairs the integrity and size of ovarian follicles in a bovine model.

There is a growing regulatory and scientific interest in the studies of environmental substances that are capable of interfering with the reproductive system. Among them, parabens stand out due to their widespread use and frequent detection as contaminants in human tissues and biological fluids. Therefore, we evaluated the toxic effects of butylparaben on the viability and follicular staging of bovine ovarian follicles in vitro. Fragments of ovaries from five cyclic bovine females were cultured for 44h in a minimal essential medium (MEM; control) or MEM supplemented with 50µg/mL and 100µg/mL of butylparaben (BP 50 and BP 100 groups, respectively). The ovarian fragments were subjected to follicular staging, morphological analysis, morphometric analysis, estradiol analysis and oxidative profiling. No significant changes were observed between the experimental groups in follicular staging, estradiol analysis and oxidative profile analysis. However, the BP 50 group showed a significant decrease in the number of intact ovarian follicles. Moreover, a decrease in the follicular and oocyte diameters was observed in the groups that were exposed to butylparaben. In conclusion, butylparaben impairs the integrity and size of ovarian follicles in an in vitro bovine model, but does not affect the oxidative profile and steroidogenesis.

Lung Cancer Staging Using Chest CT and FDG PET/CT Free-Text Reports: Comparison Among Three ChatGPT Large-Language Models and Six Human Readers of Varying Experience.

Background: Although radiology reports are commonly used for lung cancer staging, this task can be challenging given radiologists' variable reporting styles as well as reports' potentially ambiguous and/or incomplete staging-related information. Objective: To compare performance of ChatGPT large-language models (LLMs) and human readers of varying experience in lung cancer staging using chest CT and FDG PET/CT free-text reports. Methods: This retrospective study included 700 patients (mean age, 73.8±29.5 years; 509 male, 191 female) from four institutions in Korea who underwent chest CT or FDG PET/CT for non-small cell lung cancer initial staging from January, 2020 to December, 2023. Examinations' reports used a free-text format, written exclusively in English or in mixed English and Korean. Two thoracic radiologists in consensus determined the overall stage group (IA, IB, IIA, IIB, IIIA, IIIB, IIIC, IVA, IVB) for each report using the AJCC 8th-edition staging system, establishing the reference standard. Three ChatGPT models (GPT-4o, GPT-4, GPT-3.5) determined an overall stage group for each report using a script-based application programming interface, zero-shot learning, and prompt incorporating a staging system summary. Six human readers (two fellowship-trained radiologists with lesser experience than the radiologists who determined the reference standard, two fellows, two residents) also independently determined overall stage groups. GPT-4o's overall accuracy for determining the correct stage among the nine groups was compared with that of the other LLMs and human readers using McNemar tests. Results: GPT-4o had an overall staging accuracy of 74.1%, significantly better than the accuracy of GPT-4 (70.1%, p=.02), GPT-3.5 (57.4%, p<.001), and resident 2 (65.7%, p<.001); significantly worse than the accuracy of fellowship-trained radiologist 1 (82.3%, p<.001) and fellowship-trained radiologist 2 (85.4%, p<.001); and not significantly different from the accuracy of fellow 1 (77.7%, p=.09), fellow 2 (75.6%, p=.53), and resident 1 (72.3%, p=.42). Conclusions: The best-performing model, GPT-4o, showed no significant difference in staging accuracy versus fellows, but significantly worse performance versus fellowship-trained radiologists. The findings do not support use of LLMs for lung cancer staging in place of expert healthcare professionals. Clinical Impact: The findings indicate the importance of domain expertise for performing complex specialized tasks such as cancer staging.

Multiple Localization Analysis of the Major QTL-sfw 2.2 for Controlling Single Fruit Weight Traits in Melon Based on SLAF Sequencing.

Cucumis melo is an annual dicotyledonous trailing herb. It is fruity, cool, and refreshing to eat and is widely loved by consumers worldwide. The single fruit weight is an important factor affecting the yield, and thus the income and economic benefits, of melon crops. In this study, to identify the main QTLs (quantitative trait locus) controlling the single fruit weight of melon and thereby identify candidate genes controlling this trait, specific-locus amplified fragment sequencing (SLAF) analysis was performed on the offspring of female 1244 plants crossed with male MS-5 plants. A total of 115 individual plants in the melon F2 population were analyzed to construct a genetic linkage map with a total map distance of 1383.88 cM by the group in the early stages of the project, which was divided into 12 linkage groups with a total of 10,596 SLAF markers spaced at an average genetic distance of 0.13 cM. A total of six QTLs controlling single fruit weight (sfw loci) were detected. Seven pairs of markers with polymorphisms were obtained by screening candidate intervals from the SLAF data. The primary QTL sfw2.2 was further studied in 300 F2:3 family lines grown in 2020 and 2021, respectively, a positioning sfw2.2 between the markers CY Indel 11 and CY Indel 16, between 18,568,142 and 18,704,724 on chromosome 2. This interval contained 136.58 kb and included three genes with functional annotations, MELO3C029673, MELO3C029669, and MELO3C029674. Gene expression information for different fruit development stages was obtained from 1244 and MS-5 fruits on the 15d, 25d, and 35d after pollination, and qRT-PCR (quantitative reverse transcription-PCR) indicated that the expression of the MELO3C029669 gene significantly differed between the parents during the three periods. The gene sequences between the parents of MELO3C029669 were analyzed and compared, a base mutation was found to occur in the intronic interval between the parents of the gene, from A-G. Phylogenetic evolutionary tree analysis revealed that the candidate gene MELO3C029669 is most closely related to Pisum sativum Fimbrin-5 variant 2 and most distantly related to Cucumis melo var. makuwa. Therefore, it was hypothesized that MELO3C029669 is the primary major locus controlling single fruit weight in melon. These results not only provide a theoretical basis for further studies to find genes with functions in melon single fruit weight but also lay the foundation for accelerating breakthroughs and innovations in melon breeding.