The emotion of gratitude as a mediator between subjective happiness, positive and negative affect and satisfaction with life in Spanish adults / La emoción de gratitud como mediadora entre la felicidad subjetiva, el afecto positivo y negativo y la satisfacción con la vida en adultos españoles

El presente estudio investigó si la satisfacción con la vida se predice a partir de la felicidad subjetiva, afectos positivos y negativos, alteración psicológica y emociones de gratitud y si la emoción de gratitud está mediando la relación con la felicidad subjetiva, los afectos y la satisfacción con la vida. Se hicieron correlación de Pearson, pruebas de regresión lineal múltiple y modelos de mediación en una muestra de 1537 adultos españoles, 73.6% mujeres y 26.4% hombres, edad 18-88 años (M = 42.56 años; DT = 16.29). Se halló que las emociones de gratitud median la relación entre felicidad subjetiva y satisfacción con la vida y entre los afectos positivos y la satisfacción con la vida. Los afectos positivos son los que más se relacionan con la satisfacción con la vida, seguidos por la felicidad subjetiva y las emociones de gratitud. Los hombres están más satisfechos con la vida cuando sienten menos afecto negativo. Además, las emociones de gratitud median la relación entre felicidad subjetiva y satisfacción con la vida y entre los afectos positivos y la satisfacción con la vida. La diferencia principal radica en que las emociones de gratitud son más fuertes en las mujeres que en los hombres.(AU)

This study aims to examine the predictability of satisfaction with life on the basis of subjective happiness, positive and negative affect, psy-chological disturbance and emotion of gratitude. It also seeks to assess whether the emotion of gratitude is a mediating variable withsubjective happiness, affect, and satisfaction with life. Statistical analyses of Pearson'scorrelation, multiple linear regression tests, and mediation models were conducted on asample of 1537 Spanish adults, 73.6% were females, 26.4% males, age between 18-88 yearsold (M = 42.56; SD = 16.29). The emo-tions of gratitude were found to mediate therelationship between subjec-tive happiness and satisfaction with life and between positiveaffect and satisfaction with life. Of the variables studied, positive affect is the most related tosatisfaction with life, followed by subjective happiness and emo-tions of gratitude. Maleparticipants are more satisfied with life when they feel the less negative affect. Regardingmediation models, emotions of grat-itude mediate the relationship between subjectivehappiness and satisfac-tion with life and between positive affect and satisfaction with life. Themaindifferenceis thatemotions of gratitudearestronger infemalesthan in males.(AU)

National Implementation of CPAP Telemonitoring and a Pay-for-performance Scheme for Homecare Providers in France Leads to Prioritisation of Resources to Individuals with Low Therapy Adherence: The IMPACT-PAP Cohort Study.

INTRODUCTION: Long-term adherence to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea remains suboptimal and low adherence increases healthcare costs. This study investigated relationships between CPAP adherence and the intensity of support provided by homecare providers after implementation of telemonitoring and pay-for-performance reimbursement for CPAP in France. METHODS: Adults who started CPAP in 2018/2019, used telemonitoring, and had ≥1 year of homecare provider data were eligible. The main objective was to determine associations between CPAP adherence at 1 month (low [<2h/night], intermediate [2 to <4h/night], high [≥4h/night]) and the number/type of homecare provider interactions (home visits, phone calls, mask change) during the first year. RESULTS: Eleven thousand, one hundred sixty-six individuals were included (mean age 59.8±12.7 years, 67% male). The number of homecare provider interactions per person increased significantly as 1-month CPAP usage decreased (7.65±4.3, 6.5±4.0, 5.4±3.4 in low, intermediate and high adherence groups; p<0.01). There was marked improvement in device usage over the first 5-6 months of therapy in the low and intermediate adherence subgroups (p<0.05 after adjustment for age, sex, initial CPAP adherence, and number of interactions). After adjustment for age, sex and 1-month adherence, having 3-4 interactions was significantly associated with better 1-year adherence (odds ratio 1.24, 95% confidence interval 1.05-1.46), while having >7 interactions was significantly associated with worse 1-year adherence. CONCLUSIONS: The telemonitoring/reimbursement scheme in France had a positive impact on CPAP adherence and facilitated a more personalised approach to therapy management, focusing resources on patients with low and intermediate adherence.

ESF1 and MIPEP proteins promote estrogen receptor-positive breast cancer proliferation and are associated with patient prognosis.

BACKGROUND: Estrogen receptor-positive (ER+) breast cancer accounts for two-thirds of all breast cancers, and its early and late recurrences still threaten patients' long-term survival and quality of life. Finding candidate tumor antigens and potential therapeutic targets is critical to addressing these unmet needs. METHOD: The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to identify the differentially expressed proteins (DEPs) between ER + breast cancer and corresponding adjacent normal tissue. Candidate DEPs were screened by bioinformatic analyses, and their expression was confirmed by immunohistochemical (IHC) staining and western blot. A series of in vitro experiments, including wound healing assay, colony formation, and cell cycle assay, were performed to reveal the functions of selected DEPs. Additionally, their clinical significances were further analyzed. RESULT: A total of 369 DEPs (fold change ≥ 2.0 or ≤ 0.66, P < 0.05) were discovered. Compared with normal tissue, 358 proteins were up-regulated and 11 proteins were down-regulated in ER + breast cancer. GO and KEGG enrichment analysis showed that DEPs were closely associated with RNA regulation and metabolic pathways. STRING analysis found ESF1 and MIPEP were the hub genes in breast cancer, whose increased expressions were verified by the IHC staining and western blot. Knocking down ESF1 and MIPEP inhibited colony formation and increased cell apoptosis. Besides, knocking down ESF1 inhibited wound healing but not MIPEP. In addition, ESF1 and MIPEP expression were negatively associated with patient prognosis. CONCLUSION: The upregulation of ESF1 and MIPEP promoted ER + breast cancer proliferation, which might provide novel targets for the development of new therapies.

Development and Validation of the Maternal Drinking Motives Scale (M-DMS).

BACKGROUND: Alcohol use is a gendered behavior and motherhood is a life stage which may influence drinking motives. However, there are no drinking motive scales uniquely tailored to maternal populations. This work developed a new maternal drinking motives scale (M-DMS) and determined associations between the M-DMS and alcohol-related behavior. METHODS: An online observational survey (n = 534) and online test-retest survey (n = 164) were conducted with adult, UK mothers. From the observational study, data on drinking motives was extracted to determine M-DMS items and factor loading. This was split into two data sets for exploratory and confirmatory factor analyses. Alcohol Use Disorders Identification Test (AUDIT) and Timeline Follow back data, taken from both surveys, were combined to determine the M-DMS's predictive validity. RESULTS: Following a parallel analysis and exploratory factor analysis, a two-factor model (positive reinforcement motives, negative reinforcement motives) was deemed the best fit. Probability functional analysis identified items with problematic responses. These were removed before confirmatory factor analysis (on the second dataset) demonstrated a good fit for the two-factor model. All factor loadings were significant and positive (ßs > 0.56). Reliability of the two subscales was excellent: negative reinforcement (ωT = 0.95), positive reinforcement (ωT = 0.89). Test-retest reliability was good for both negative (ICC = 0.84, 95%CI = 0.80-0.88) and positive (ICC = 0.77, 95% CI = 0.71-0.82) subscales. Both subscales predicted AUDIT and quantity of alcohol consumption (ps < 0.001). CONCLUSION: The first tailored Maternal Drinking Motives Scale (M-DMS) provides a more valid research tool for assessing psychological mechanisms of alcohol use in mothers.

Effect of positive end expiratory pressure on non-hypoxic apnea time and atelectasis during induction of anesthesia in infant: A randomized controlled trial.

INTRODUCTION: This study aimed to assess the impact of positive-end-expiratory pressure (PEEP) on the non-hypoxic apnea time in infants during anesthesia induction with an inspired oxygen fraction of 0.8. METHODS: This age stratified randomized controlled trial included patients under 1 year of age. Preoxygenation was performed using an inspired oxygen fraction of 0.8 for 2 min. Inspired oxygen fraction of 0.8 was administered via a face mask with volume-controlled ventilation at a tidal volume of 6 mL.kg-1, with or without 7 cmH2O of PEEP. Tracheal intubation was performed after 3 min of ventilation; however, it was disconnected from the breathing circuit. Ventilation was resumed once the pulse oximetry readings reached 95%. The primary outcome was the non-hypoxic apnea time, defined as the time from the cessation of ventilation to achieving a pulse oximeter reading of 95%. The secondary outcome measures included the degree of atelectasis assessed by ultrasonography and the presence of gastric air insufflation. RESULTS: Eighty-four patients were included in the final analysis. In the positive end-expiratory pressure group, the atelectasis score decreased (17.0 vs. 31.5, p < .001; mean difference and 95% CI of 11.6, 7.5-15.6), while the non-hypoxic apnea time increased (80.1 s vs. 70.6 s, p = .005; mean difference and 95% CI of -9.4, -16.0 to -2.9), compared to the zero end-expiratory pressure group, among infants who are 6 months old or younger, not in those aged older than 6 months. DISCUSSION: The application of positive end-expiratory pressure reduced the incidence of atelectasis and extended the non-hypoxic apnea time in infants who are 6 months old or younger. However, it did not affect the incidence of atelectasis nor the non-hypoxic apnea time in patients aged older than 6 months.

Long-term consequences of positive surgical margin after partial nephrectomy for renal cell carcinoma: multi-institutional analysis.

INTRODUCTION: The aim of the study was to determine the impact of positive surgical margins (PSM) after PN on very long-term recurrence in a contemporary cohort. METHODS: Patients who underwent PN for a localized renal tumour were included. Patients were stratified according to the presence of PSM. Data on patients' characteristics, the tumour, the peri- and postoperative events were collected. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method and compared by the log-rank test. Sensitivity analyses using weighted propensity score analysis was performed to account for potential selection biases arising from the nonrandom allocation of patients to different groups. RESULTS: A total of 1115 patients were included in the study. The incidence of PSM was 5.4% (n = 61). The median follow-up time was 51 months for the PSM group and 61 months for the NSM group (p = 0.31). Recurrence rates were significantly higher in the PSM group (13%, n = 8) compared to the NSM group (7%, n = 73) (p = 0.05). This resulted in a significant reduction in DFS in the PSM group (p = 0.004), particularly pronounced in patients with clear cell renal cell carcinoma. Additionally, OS was significantly lower in the PSM group (p < 0.01). Propensity score analysis confirmed a decrease in DFS for the PSM group (p = 0.05), while there was no significant difference in OS between the two groups (p = 0.49). CONCLUSION: In this retrospective multicenter study, PSM impact on oncological outcomes, increasing recurrence, but no difference in OS was observed post-adjustment for biases.

Survival outcomes and failure patterns for oropharyngeal cancers treated with simultaneous integrated boost in intensity modulated radiotherapy (SIB-IMRT) and concurrent chemotherapy.

BACKGROUND: Intensity modulated radiotherapy (IMRT) has become a standard radiotherapy treatment delivery option owing to the advantages it offers in terms of target coverage and organ sparing. Furthermore, the ability to introduce different fractionation for different targets lets us deliver higher doses to the high-risk areas and lower doses to the elective volumes at the same sitting, referred to as simultaneous integrated boost (SIB). In the current study, we intended to retrospectively analyze the clinical outcomes and patterns of the failure of oropharyngeal cancers treated with SIB-IMRT and concurrent chemotherapy at our centre and analyze the factors contributing to poorer outcomes. MATERIAL AND METHODS: Data of oropharyngeal cancer patients treated with SIB-IMRT and concurrent chemotherapy were retrieved from the institutional database. Patient demographic details, histopathological features, staging, treatment details, failure patterns and outcomes were documented. All potential factors were evaluated for outcomes. Radiation was delivered by using the SIB-IMRT technique. High-risk planning target volume (PTV) received 66 Gy in 2.2 Gy/fraction, intermediate and low-risk PTV received 60 Gy and 54 Gy, respectively. Primary endpoint was to assess local control (LC), regional control (RC) and loco-regional control (LRC) rates and secondary end point was to evaluate the survival outcomes - overall survival (OS) and cancer-specific mortality. All survival analyzes were performed using the Kaplan-Meier method. RESULTS: A total of 169 cases were included in the final analysis. The median age was 55 years (range 20-78) with 95.3% males. The base of tongue was the most common primary site. Around 54% cases were node negative with 38% patients having stage IV disease. The local control rates for N0 vs. N+ cases were 74.1 vs. 62.3% (P = 0.046), respectively. Similarly, the 4-year RC rates for N0 vs. N+ cases were 94.4 vs. 83.5% (P = 0.024), respectively. On multivariate analysis, only 4-year RC rates showed significant difference between the two (P = 0.039). No differences were found between T stages in LRC and OS. The 4-year LRC rates for stages 1, 2 vs. 3, 4 were non-significant (69.2 vs. 66.3%; P = 0.178). The 4-year OS rate was 81.3%. The 4-year LC and LRC rates were 67.8 and 89.5%, respectively. There were 54 local and 17 regional failures. The median time to failure was 13 months (range 3.6-82.9). CONCLUSION: SIB-IMRT provides comparable outcomes for oropharyngeal cancers. OS and loco-regional recurrences were significantly worse for nodal positive disease.

Positive feedback loop of c-myc/XTP6/NDH2/NF-κB to promote malignant progression in glioblastoma.

BACKGROUND: Recent studies have highlighted the significant role of the NF-κB signaling pathway in the initiation and progression of cancer. Furthermore, long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in sustaining the NF-κB signaling pathway's functionality. Despite these findings, the underlying molecular mechanisms through which lncRNAs influence the NF-κB pathway remain largely unexplored. METHODS: Bioinformatic analyses were utilized to investigate the differential expression and prognostic significance of XTP6. The functional roles of XTP6 were further elucidated through both in vitro and in vivo experimental approaches. To estimate the interaction between XTP6 and NDH2, RNA pulldown and RNA Immunoprecipitation (RIP) assays were conducted. The connection between XTP6 and the IκBα promoter was examined using Chromatin Isolation by RNA Purification (ChIRP) assays. Additionally, Chromatin Immunoprecipitation (ChIP) assays were implemented to analyze the binding affinity of c-myc to the XTP6 promoter, providing insights into the regulatory mechanisms at play. RESULTS: XTP6 was remarkedly upregulated in glioblastoma multiforme (GBM) tissues and was connected with adverse prognosis in GBM patients. Our investigations revealed that XTP6 can facilitate the malignant progression of GBM both in vitro and in vivo. Additionally, XTP6 downregulated IκBα expression by recruiting NDH2 to the IκBα promoter, which resulted in elevated levels of H3K27me3, thereby reducing the transcriptional activity of IκBα. Moreover, the progression of GBM was further driven by the c-myc-mediated upregulation of XTP6, establishing a positive feedback loop with IκBα that perpetuated the activation of the NF-κB signaling pathway. Notably, the application of an inhibitor targeting the NF-κB signaling pathway effectively inhibited the continuous activation induced by XTP6, leading to a significant reduction in tumor formation in vivo. CONCLUSION: The results reveal that XTP6 unveils an innovative epigenetic mechanism instrumental in the sustained activation of the NF-κB signaling pathway, suggesting a promising therapeutic target for the treatment of GBM.

Genomic Alterations Correlated to Trastuzumab Resistance and Clinical Outcomes in HER2+/HR- Breast Cancers of Patients Living in Northwestern China.

Anti-HER2 therapy has significantly improved the survival rates of patients with HER2+ breast cancer. However, a subset of these patients eventually experience treatment failure, and the underlying genetic mechanisms remain largely unexplored. This underscores the need to investigate the genomic heterogeneity of HER2+ breast cancer. In this study, we focus on HER2+/HR- breast cancer, as it differs from HER2+/HR+ breast cancer in terms of genetic and biological characteristics. We performed gene-targeted genome sequencing on 45 HER2+/HR- breast cancer samples and identified 650 mutations across 268 cancer-related genes. TP53 (71.1%) and PIK3CA (35.6%) were the most frequently mutated genes in our sample. Additionally, ERBB2 (77.8%), CDK12 (42.2%), and MYC (11.1%) exhibited a high frequency of copy number amplifications (CNAs). Comparative analysis with two other HER2+/HR- breast cancer cohorts revealed that our cohort had higher genetic variation rates in ARID1A, PKHD1, PTPN13, FANCA, SETD2, BRCA2, BLM, STAG2, FAT1, TOP2A, POLE, ATM, KMT2B, FGFR4, and EPAS1. Notably, in our cohort, NF1 and ATM mutations were more prevalent in trastuzumab-resistant patients (NF1, p=0.016; ATM, p=0.006) and were associated with primary trastuzumab resistance (NF1, p=0.042; ATM, p=0.021). Moreover, patients with NF1 mutations (p=0.009) and high histological grades (p=0.028) were more likely to experience early relapse. Ultimately, we identified a unique cancer-related gene mutation profile and a subset of genes associated with primary resistance to trastuzumab and RFS in patients with HER2+/HR- breast cancer in Northwest China. These findings could lay the groundwork for future studies aimed at elucidating the mechanisms of resistance to trastuzumab and improving HER2-targeted treatment strategies.

A Novel Signature Based on Angiogenesis-Related Genes Predicts the Prognosis and Immunotherapy Response in HER2-Positive Breast Cancer.

Background: HER2-positive breast cancer is one of the most prevalent subtypes of breast cancer and represents a significant health concern for women worldwide due to its high morbidity and mortality rates. Recent studies have consistently underscored the pivotal role of angiogenesis in the development and progression of HER2-positive breast cancer. Here, we developed a prognostic signature based on angiogenesis-related genes (ARGs) to categorize HER2-positive breast cancer patients and provide insights into their survival outcomes. Methods: Kaplan-Meier survival curve, time-dependent receiver operating characteristic (ROC) and nomogram were performed to investigate the prognostic performance of the signature. In addition, we comprehensively analyzed the correlation of the prognostic signature with immune cell infiltration, immune checkpoint inhibitors (ICIs) therapy. Finally, Immunohistochemistry (IHC) and immunoblotting were used to investigate XBP1 expression in HER2-positive breast cancer tissues. Colony formation assay was performed to examine cell proliferation of HER2-positive breast cancer cells. Results: The Kaplan-Meier curves and the ROC curves demonstrated that the ARGs had good performance in predicting the prognosis of HER2-positive breast cancer patients. In addition, we observed that the low-risk group was remarkably associated with immune infiltration and better response to ICIs. Further experimental results show that XBP1 is upregulated in human HER2-positive breast cancer, and its knockdown significantly inhibited cell proliferation. Conclusions: Our study demonstrated that the ARGs could serve as a novel biomarker for predicting the prognosis of patients with HER2-positive breast cancer and providing new insights into immunotherapy strategies for these patients.

CD34-Negative Malignant Renal Solitary Fibrous Tumor: Case Report and Diagnostic Insights.

Solitary fibrous tumors (SFTs) are rare fibroblastic neoplasms with diverse biological behaviors and widespread distribution. Primary renal SFTs are uncommon, and their malignant variants, especially those that are CD34 negative, are even rarer. This study presents a case of malignant renal SFT in a 57-year-old female, focusing on its immunomorphological features. On gross examination, the tumor's large size (11.5 cm) was remarkable. Microscopic analysis showed high cellularity, diffuse sheets of moderately pleomorphic ovoid cells, prominent staghorn vessels, tumor cell necrosis, and a high mitotic count. Immunohistochemistry revealed strong positivity for STAT6, vimentin, and Bcl-2 and, notably, negativity for CD34. The presence of the NAB2::STAT6 gene fusion was confirmed through fluorescence in situ hybridization. This case emphasizes the need to consider SFT in the differential diagnosis of unusual renal tumors, even when CD34 is negative. The infrequency, morphological diversity, and resemblance to other tumors make diagnosing renal SFTs challenging. Accurate identification and classification as benign or malignant are crucial for proper clinical management and prognosis.

An Observational Study on C-Reactive Protein to Platelet Ratio in Neonatal Sepsis.

BACKGROUND: Neonatal sepsis is a serious medical condition affecting many individuals in the developing world. C-reactive protein (CRP) level in serum and platelet counts have been reported to have role in diagnosis of neonatal sepsis. OBJECTIVE: To evaluate the CRP to Platelet ratio (CPR) in relation to time and blood culture reports in neonatal sepsis patients from a tertiary care centre in the Marathwada region of Maharashtra. METHODS: The present observational study was conducted at the level III Neonatal Intensive Care Unit of a tertiary care centre in Aurangabad city of Marathwada region in Maharashtra from September 2022 to July 2023. The study included 120 neonates (delivered after completion of 28-42 weeks of gestation) with clinical/culture-positive sepsis. The newborns of seropositive mothers, neonates delivered in other hospitals, babies with congenital dysmorphic features, and babies requiring surgical procedures were excluded from the study. Blood samples for complete blood count (CBC) and CRP were collected on days 1, 3 and 5. Blood cultures were sent on day 1 of illness. Repeated measures ANOVA was used to compare the parameters of CPR, CRP, and platelet count in blood culture-positive and blood culture-negative neonatal sepsis patients on days 1, 3 and 5. RESULTS: Blood culture was positive in 37 (30.8%) cases. A repeated measures ANOVA showed a significant overall difference in the CPR across days 1, 3, and 5 (p = 0.006). The CPR was significantly higher in culture-positive neonates compared to culture-negative neonates (p = 0.042). CONCLUSION: Higher CPR in blood culture-positive neonates compared to blood culture-negative neonates supports the role of CPR in the diagnosis and management of neonatal sepsis.

The moderating role of early-life parental adverse and positive factors in the genetic and environmental contributions to objectively assessed sleep duration in middle childhood.

Early-life positive and adverse parental factors, such as positive parent personality and parental stress, affect the environmental context in which children develop and may influence individual differences in children's sleep health. This study examined the moderating role of early-life parental factors in the heritability (i.e., the extent to which individual differences are due to genetic influences) of objectively assessed childhood sleep duration. A total of 351 families from the Arizona Twin Project were studied. Primary caregivers (95% mothers) reported on multiple dimensions of stress and facets of their own personality when the twins were 12 months old. Seven years later (Mage = 8.43 years, SD = 0.68), families completed a home visit, and twins (51% female; 57% White, 29% Hispanic; 30% monozygotic, 39% same-sex dizygotic, 31% other-sex dizygotic) wore actigraph watches to assess their sleep, with caregivers completing similar assessments on their personality attributes and stress. Early-life positive parent personality moderated the heritability of sleep duration (Δ-2LL [-2 log likelihood] = 2.54, Δdf = 2, p = .28), such that as positive parent personality increased, the heritability of duration decreased. Early-life parental stress also moderated the genetic contribution to sleep duration (Δ-2LL = 2.02, Δdf = 2, p = .36), such that as stress increased, the heritability of duration increased. Concurrent positive parent personality and parental stress composites showed similar patterns of findings. Results highlight the likely contribution of parent positive traits and adverse experiences to the etiology of children's sleep health, with genetic influences on children's sleep more prominent in "riskier" environments. Understanding how genetics and environments work together to influence the etiology of sleep may inform prevention programs.

Sleep apnea after stroke: A novel target.

Sleep apnea is an independent risk factor for cerebrovascular diseases. Its prevalence in stroke survivors is high and the disorder negatively affects patients' outcomes. Despite the importance of sleep apnea assessment is highlighted also in the current guidelines, a high proportion of patients remain undiagnosed and lose the potential benefit of positive airway pressure treatment. The current paper describes links between sleep apnea and stroke. It focuses on the challenges of the diagnostic and therapeutical process and provides a brief insight into ongoing trials that could help to identify appropriate diagnostic and therapeutic approaches, their timing, and the patient population for whom treatment could be most beneficial.

Exploring positive welfare measures: preliminary findings from a prototype protocol in loose housing dairy cattle farms.

Introduction: Following the increasing interest about the development of indicators of positive welfare and affective state in farm animals, the aim of this research is to present some preliminary results on the application of a prototype protocol based exclusively on positive welfare measures and to suggest potential benefits that can promote positive welfare. Methods: The protocol was applied in 20 loose housing dairy cattle farms (6 on deep litter with straw, 14 in cubicles) and included only indicators of positive welfare and emotional states: feeding and resting synchronization, rumination during resting, comfortable lying postures, no visible eye white, relaxed ear postures, percentage of cow contacts with humans in the Avoidance Distance test. Potential benefits in terms of housing, feeding and management were then related to these variables (Mann-Whitney U test). Qualitative Behavior Assessment (QBA) was also carried out and analyzed by Principal Component Analysis to explore the effect of factors that were not evenly distributed in our sample (number of feed distributions, access to pasture, presence of paddock or environmental enrichments, automatic milking systems). Results: When hay was included in the diet, higher feeding synchronization (93.7 ± 1.6 vs. 52.2 ± 4.7%; p < 0.01), percentage of cows with relaxed ear postures (35.8 ± 5.4 vs. 15.5 ± 2.1%; p < 0.01) and percentage of cows with no visible eye white (55.9 ± 17.0 vs. 36.6 ± 4.1%; n.s.) were recorded. A higher level of feeding synchronization was observed also when the feeding places/cow ratio was > 1 (72.1 ± 9.9 vs. 53.8 ± 5.8%), although differences were not significant (p = 0.14). Deep litter had a more positive effect than cubicles on comfort at resting, with a significantly higher percentage of ruminating cows (65.8 ± 10.2 vs. 34.2 ± 3.7%; p < 0.01), a higher percentage of cows with no visible eye white (55.6 ± 9.9 vs. 33.1 ± 3.7%; p < 0.05) and a higher percentage of cows in a more comfortable posture, with stretched legs (14.3 ± 5.1 vs. 5.6 ± 1.6%; p = 0.09). QBA highlighted the most positive emotional state in the only farm that allowed access to pasture. Conclusions: This study represents a first attempt to apply a protocol for on-farm welfare evaluation based exclusively on the use of positive welfare indicators and provides suggestions on possible benefits (e.g., deep litter, feeding places/cow ratio > 1, hay in the diet and access to pasture) to enhance dairy cattle welfare.

Proteomic and metabolomic profiling of methicillin resistant versus methicillin sensitive Staphylococcus aureus using a simultaneous extraction protocol.

Background: Understanding the biology of methicillin resistant Staphylococcus aureus (MRSA) is crucial to unlocking insights for new targets in our fight against this antimicrobial resistant priority pathogen. Although proteomics and metabolomic profiling offer the potential to elucidating such biological markers, reports of methodological approaches for carrying this out in S. aureus isolates remain limited. We describe the use of a dual-functionality methanol extraction method for the concurrent extraction of protein and metabolites from S. aureus and report on the comparative analysis of the proteomic and metabolomic profiles of MRSA versus methicillin sensitive S. aureus (MSSA). Methods: Bacterial reference strains MRSA ATCC43300 and MSSA ATCC25923 were used. The conventional urea methodology was used for protein extraction and a methanol based method was used for concurrent proteins and metabolites extraction. Proteomic and metabolomic profiling was carried out using TimsTOF mass spectrometry. Data processing was carried out using the MaxQuant version 2.1.4.0. Results: This study represents the first report on the utilization of the methanol extraction method for concurrent protein and metabolite extraction in Gram positive bacteria. Our findings demonstrate good performance of the method for the dual extraction of proteins and metabolites from S. aureus with demonstration of reproducibility. Comparison of MRSA and MSSA strains revealed 407 proteins with significantly different expression levels. Enrichment analysis of those proteins revealed distinct pathways involved in fatty acid degradation, metabolism and beta-lactam resistance. Penicillin-binding protein PBP2a, the key determinant of MRSA resistance, exhibited distinct expression patterns in MRSA isolates. Metabolomic analysis identified 146 metabolites with only one exclusive to the MRSA. The enriched pathways identified were related to arginine metabolism and biosynthesis. Conclusion: Our findings demonstrate the effectiveness of the methanol-based dual-extraction method, providing simultaneous insights into the proteomic and metabolomic landscapes of S. aureus strains. These findings demonstrate the utility of proteomic and metabolomic profiling for elucidating the biological basis of antimicrobial resistance.

Prognostic prediction and comparison of three staging programs for patients with advanced (T2-T4) esophageal squamous carcinoma after radical resection.

Purpose: Lymph node-based staging protocols are frequently employed to evaluate the prognosis of esophageal cancer, yet their accuracy remains contentious. The present study was conducted to assess the prognostic significance of three lymph node staging systems, namely N stage, lymph node rate (LNR), and log odds of positive lymph nodes (LODDS), in patients diagnosed with advanced (T2-T4) esophageal squamous cell carcinoma (ESCC). Methods: This cohort comprised 319 eligible patients, with an additional 409 individuals retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, forming the validation cohort. Differences in overall survival (OS) of patients between groups were assessed using the log-rank test. Prognostic independent risk variables were identified, and lymph nodes (LN) prognostic models were built using multivariate Cox regression analysis. Besides, the predictive accuracy of each model was evaluated utilizing the (-2) log-likelihood ratio (-2LLR), the likelihood ratio χ2 score (LRχ2), the Akaike information criterion (AIC), and Harrell's concordance index (C-index). To further evaluate the potential superiority of the model, a nomogram was constructed for comparison with the conventional Tumor Node Metastasis (TNM) staging approach. Results: Independent prognostic factors for advanced ESCC include the N stage, LNR, and LODDS. Herein, LODDS presented higher values for C-index and LRχ2, and lower values for AIC and -2LLR in OS compared to the others. Consequently, a nomogram was constructed based on LODDS. Calibration curves exhibited strong agreement, and assessment through C-index, receiver operating characteristic (ROC) curves, and clinical decision curve analysis (DCA) demonstrated promising clinical applicability. Conclusion: LODDS emerges as a promising future prognostic indicator. After surgery, the proposed model holds the potential to provide valuable treatment recommendations for patients with advanced ESCC.

The level of discomfort during the use of different circuits of the mechanical ventilator.

Objectives: Endotracheal tube (ETT) intubation is a life-saving procedure in patients with respiratory failure. However, the presence of an ETT can cause significant discomfort. A tracheostomy tube is used to administer a mechanical ventilator, resulting in a more stable airway and fewer serious injuries. Noninvasive ventilators (NIPPVs) administer ventilation through masks and must be tightly fixed to the face. ETT, tracheostomy, and NIPPV are the most common methods of ventilator maintenance. However, these interventions often cause discomfort to patients. This study aimed to compare discomfort associated with ETT, tracheostomy, and NIPPV. Materials and Methods: Forty-nine conscious patients with postextubation NIPPV and eight conscious patients who underwent postextubation tracheotomy were evaluated for discomfort. A questionnaire survey on discomfort was performed before and after NIPPV or tracheostomy. These patients reported their level of discomfort on a visual analog scale. Results: The levels of sore throat, nasal pain, body pain, activity limitation, respiratory discomfort, oral discomfort, difficulty coughing sputum, worry about respiratory tube disconnection, back pain, anxiety, worry about long-term admission, sleep disturbance, and general discomfort during ETT intubation were higher than during tracheostomy or NIPPV (all P < 0.05). The mean level of discomfort was approximately 5-6 points (moderate) in patients with ETT and 2-3 points (mild) in patients with NIPPV or tracheostomy. Conclusion: The level of discomfort was higher in patients who underwent ETT intubation than in those who underwent NIPPV or tracheostomy. However, the level of discomfort was similar between the patients with NIPPV and those who underwent tracheostomy.

Epstein-Barr Virus-Positive Mucocutaneous Ulcer With Medication-Related Osteonecrosis of the Jaw Arising in the Mandible of a Rheumatoid Arthritis Patient: A Case Report.

This study presents a rare case of an Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) co-existing with medication-related osteonecrosis of the jaw (MRONJ) in the mandible of a 54-year-old Japanese man who complained of painful swelling of the left mandibular gingiva over the past three months. The patient had a history of methotrexate (MTX) and bisphosphonates (BPs) use. Intraoral examination revealed a 35 mm large ulcerative lesion with marginal gingival swelling and bone exposure on the left side of the mandible. A biopsy was performed, confirming the diagnosis of EBVMCU with MRONJ. Due to the enlargement of the bone exposure, marginal resection of the mandible was performed under general anesthesia as a treatment for residual MRONJ. At the two-year follow-up, no evidence of recurrence was observed.

Efficacy and safety of first-line regimens for advanced HER2-positive breast cancer: A Bayesian network meta-analysis.

Background: The current standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is pertuzumab plus trastuzumab and docetaxel as first-line therapy. However, with the development of newer treatment regimens, there is a lack of evidence regarding which is the optimal treatment strategy. The aim of this network meta-analysis was to evaluate the efficacy and safety of first-line regimens for advanced HER2-positive breast cancer by indirect comparisons. Methods: A systematic review and Bayesian network meta-analysis were conducted. The PubMed, EMBASE, and Cochrane Library databases were searched for relevant articles published through to December 2023. The hazard ratio (HR) and 95% credible interval (CrI) were used to compare progression-free survival (PFS) between treatments, and the odds ratio and 95% CrI were used to compare the objective response rate (ORR) and safety. Results: Twenty randomized clinical trials that included 15 regimens and 7094 patients were analyzed. Compared with the traditional trastuzumab and docetaxel regimen, PFS was longer on the pyrotinib and trastuzumab plus docetaxel regimen (HR: 0.41, 95% CrI: 0.22-0.75) and the pertuzumab and trastuzumab plus docetaxel regimen (HR: 0.65, 95% CrI: 0.43-0.98). Consistent with the results for PFS, the ORR was better on the pyrotinib and trastuzumab plus docetaxel regimen and the pertuzumab and trastuzumab plus docetaxel regimen than on the traditional trastuzumab and docetaxel regimen. The surface under the cumulative ranking curve indicated that the pyrotinib and trastuzumab plus docetaxel regimen was most likely to rank first in achieving the best PFS and ORR. Comparable results were found for grade ≥3 AE rates of ≥10%. Conclusions: Our results suggest that the pyrotinib and trastuzumab plus docetaxel regimen is most likely to be the optimal first-line therapy for patients with HER2-positive breast cancer.