Search Results (185)

Background: The prevalence of cardiogenic shock (CS) resulting from the progression of heart failure (PHF) is increasing and remains associated with high mortality. This study aimed to compare the clinical characteristics and outcomes of patients who developed CS due to PHF versus those whose CS was caused by other aetiologies (non-PHF). Methods: We retrospectively analysed 280 patients admitted to a Polish tertiary care centre between January 2021 and April 2024. The cohort was divided into two groups: PHF (n = 84, 30%) and non-PHF (n = 196, 70%). Results: Compared to the non-PHF group, PHF patients more frequently had chronic kidney disease (30% vs. 15%, p < 0.01), and significant valvular disease (30% vs. 13%, p < 0.01). PHF patients exhibited significantly lower white blood cell counts (9.4 [6.9–16.4] vs. 13.3 [10.4–17.6], p < 0.01) and troponin T levels (188 [61–1392] vs. 10,921 [809–45,792], p < 0.01). In-hospital mortality was significantly lower among PHF patients (52% vs. 65%, p = 0.04). Although the overall use of mechanical circulatory support (MCS) did not differ between groups, significant differences in the types of MCS applied were observed (p < 0.01). Additionally, PHF patients underwent fewer coronary revascularisation procedures (15% vs. 70%, p < 0.01). Conclusions: Patients with PHF-related CS exhibit distinct clinical profiles and may experience lower in-hospital mortality when appropriately diagnosed and treated with a personalised approach. Further prospective, multicentre studies are warranted to optimize the management of this growing subgroup of CS patients. Full article

Background/Objectives: Guidelines recommend patients with heart failure with reduced ejection fraction (HFrEF) receive four-pillar heart failure (4P-HF) therapy, which significantly reduces cardiac morbidity and mortality. However, implementing these guidelines effectively into clinical practice remains challenging. Methods: Patients with HFrEF on submaximal 4P-HF therapy were identified from a large, multicentre Cardiology network database using a natural language processing tool, supported by manual file review. A nurse-led, remotely delivered, medication uptitration program aimed to optimise therapy in this real-world cohort. Results: The final cohort included 2004 patients with a mean age of 72.7 ± 11.6 years. Utilisation of 4P-HF increased from 11.1% at baseline to 49.8% post intervention, and each individual medication class increased significantly post intervention (all p < 0.001). The largest increase was observed with the use of sodium–glucose cotransporter 2 inhibitors, which rose from 17.3% to 73.9%, followed by mineralocorticoid receptor antagonists (51.6% to 65.7%), beta-blockers (88.4% to 97.0%), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor blocker–neprilysin inhibitors (89.8% to 96.4%). In patients on submaximal therapy, barriers were documented in all cases. Following medication optimisation, left ventricular ejection function (LVEF) improved significantly (38.5% ± 10.8% vs. 42.5% ± 11.7, p < 0.001). Conclusions: This nurse-led, remotely delivered, medication optimisation program significantly improved the adoption of 4P-HF therapy and LVEF in patients with HFrEF. The program demonstrates a practical, scalable solution for the optimisation of HFrEF therapy across a large healthcare network. Full article

In order to increase the toughness of poly(hexamethylene furandicarboxylate) (PHF) without severely compromising its strength at break, novel biobased poly(hexamethylene furandicarboxylate-co-hexamethylene thiophenedicarboxylate) (PHFTh) copolyesters and their parent homopolyesters, PHF and poly(hexamethylene thiophenedicarboxylate), were successfully synthesized through melt polycondensation in this research. Despite the variation in their compositions, all the PHFTh copolyesters exhibited excellent thermal stability. The PHFTh copolyesters were semicrystalline in nature, showing the lowest eutectic melting points and isodimorphism behaviors over the whole composition range. As the hexamethylene thiophenedicarboxylate (HTh) unit content increased, the glass transition temperature of the copolyesters gradually decreased, while the chain mobility was accordingly enhanced. Therefore, the introduction of the HTh unit significantly increased the elongation at break of the PHFTh, achieving a balance between strength and toughness. The biobased PHFTh copolyesters showed tunable thermal behaviors and excellent mechanical properties and may find potential end uses from a practical application viewpoint. Full article

Plant homeodomain (PHD) finger protein 20-like 1 (PHF20L1) is a novel epigenetic “reader” that specifically recognises histone post-translational modifications (PTMs) via its Tudor and PHD finger domains, thereby regulating chromatin remodelling, DNA damage repair, and oncogene transcriptional activation. This review comprehensively summarises the role of PHF20L1 in various cancers, including breast, ovarian, and colorectal cancers, as well as retinoblastomas, and elucidates its molecular mechanisms of action in cancer pathogenesis. Accumulating evidence indicates that PHF20L1 is upregulated in these malignancies and drives tumour progression by promoting proliferation, metastasis, and immune evasion. Furthermore, PHF20L1 orchestrates tumour-related gene expression by interacting with key epigenetic complexes. Given its unique structural features, we propose novel strategies for developing small-molecule inhibitors and combinatorial therapies, providing a theoretical basis for targeted epigenetic regulation for precision treatment. Future research should further investigate the molecular regulatory networks of PHF20L1 in different cancers and other human diseases and focus on developing specific small-molecule inhibitors to enable precision-targeted therapies. Full article

Recent pan-cancer transcriptome analysis has revealed differential activity of two alternative PHF19 gene promoters in malignant versus non-malignant gut mucosa. One of these promoters upregulated in colon cancer leads to the expression of the PHF19-207 transcript, suggesting its potential role in tumor promotion. The objective of this study was to investigate the function of PHF19-207 using in silico tools and publicly available data, as well as to assess its expression in colon cancer. Expression analyses were conducted via qPCR and RNA sequencing on RNA extracted from the immortalized colonic epithelial cell line HCEC-1CT, as well as a series of colon cancer cell lines cultured in both 2D and 3D environments. The expression of PHF19-207 was found to be elevated in all malignant cell lines compared to the non-malignant HCEC-1CT cell line in both culture conditions, with the most prominent increase observed in cell lines derived from advanced stages of the disease and in the HCEC-1CT cell line overexpressing KRAS. Furthermore, the PHF19-207 transcript was detected in exosomes derived from malignant cells. These findings suggest that PHF19-207 holds potential as a diagnostic biomarker. In addition, in silico analyses indicate that this transcript may function as a long non-coding RNA involved in the regulation of gene expression. Further functional investigations are required to elucidate its precise role in colon carcinogenesis. Full article

Background and Objectives: This retrospective cohort study aimed to evaluate the predictive validity of four frailty indices—Modified Frailty Index-5 (mFI-5), Edmonton Frail Scale (EFS), Clinical Frailty Scale (CFS), and Trauma-Specific Frailty Index (TSFI)—in forecasting postoperative complications and functional outcomes in elderly patients with proximal humerus fractures (PHFs) treated either surgically or conservatively. Materials and Methods: A total of 244 patients aged ≥60 years with PHFs treated at Erzurum Hospital between January 2018 and January 2023 were included. Patients were categorized into surgical (n = 110) and conservative (n = 134) groups. Surgical procedures included open reduction and internal fixation (n = 88), hemiarthroplasty (n = 10), and reverse shoulder arthroplasty (n = 12). Frailty was retrospectively assessed using mFI-5, EFS, CFS, and TSFI based on 24-month follow-up data. Outcomes included complications, reoperations, rehospitalizations, and functional results measured by the American Shoulder and Elbow Surgeons (ASES) score. Results: The overall complication rate was 13.1%, with nonunion being the most common. Reoperation and rehospitalization rates were 10.6% and 20%, respectively. The mean ASES score was 71.3 ± 15.2, with 60% of patients achieving good or excellent outcomes. Frailty scores, particularly mFI-5 and EFS, were significantly higher in the conservatively treated group compared to the surgical group (p < 0.01). Across both treatment modalities, patients with higher frailty scores had significantly increased complication rates; however, this effect was more pronounced in the surgical group. Multivariate logistic regression revealed that mFI-5 significantly predicted complications, reoperations, and rehospitalizations (p < 0.001). EFS was associated with reoperation risk (p = 0.018), while CFS and TSFI were not significantly correlated with any of the outcomes. Conclusions: Among the evaluated indices, mFI-5 showed the strongest predictive accuracy for adverse outcomes in elderly PHF patients. Notably, the negative impact of frailty was more evident among surgically treated patients. Routine frailty assessment may facilitate better risk stratification and individualized treatment planning in this population. Full article

Background: Displaced proximal humerus fractures (PHFs) in adults represent a common orthopedic challenge, especially in elderly patients with compromised bone quality. Intramedullary nails (IM) and locking plates (LP) are the most widely used fixation techniques, though the literature remains inconclusive regarding their comparative efficacy. Methods: This retrospective cohort study included 187 patients (mean age: 65.4 years) treated surgically for Neer ≥ 2-part proximal humerus fractures at a single tertiary referral center between 2018 and 2023. Patients underwent either IM nailing or LP fixation. Baseline characteristics included age, sex, smoking status, ASA score, trauma mechanism, and bone quality (assessed by the Deltoid Tuberosity Index). Functional outcomes (DASH and Constant–Murley scores), range of motion (ROM), radiographic healing, and complications were evaluated at 1, 3, 6, and 12 months postoperatively. Results were stratified by fracture type (two-, three-, and four-part fractures) and treatment group. Results: At 12 months, no statistically significant differences were found between groups in terms of DASH (p = 0.484) or Constant–Murley scores (p = 0.057). ROM recovery was comparable across all time points. Stratified analysis showed similar outcomes across fracture types. Age, smoking, and bone quality did not significantly influence clinical results. The overall complication rate was 11.8%, with no significant difference between groups. Avascular necrosis and hardware-related issues occurred predominantly in four-part fractures. Conclusions: Both intramedullary nailing and locking plate fixation provided comparable short-term outcomes for displaced PHFs. Functional recovery appeared more dependent on fracture complexity than on the choice of implant. Surgical technique should therefore be selected based on fracture morphology, patient characteristics, and surgeon experience. Full article

Urban traffic congestion poses significant challenges to sustainable development in rapidly growing cities. This study examines the spatiotemporal dynamics of traffic congestion in Enugu, Nigeria, a representative mid-sized sub-Saharan city, through a comprehensive analysis of volumetric traffic flows along three major distributors: Abakpa, Nike, and Trans-Ekulu Road. The research employed direct observation and vehicle counts, conducting a week-long traffic census during peak morning (7:30–9:30 AM) and evening (4:00–8:00 PM) periods. Data was analyzed using peak hour factor (PHF), mean plots, and chi-square tests. The results reveal a daily mean of 2334 vehicles/h. Abakpa/Nike Road demonstrated the highest traffic volumes (mean = 809.2 vehicles/h) and most concentrated peak flows (PHF = 0.79), while Trans-Ekulu Road exhibited lower, more uniformly distributed volumes (mean = 719.4 vehicles/h, PHF = 0.93). Evening peaks (6:00–8:00 PM) consistently surpassed morning volumes, with Abakpa/Nike Road reaching 974 vehicles/hour during the evening rush compared to 620 vehicles/hour in the mornings. Chi-square analysis (χ² = 55.5, df = 8) confirmed statistically significant differences in flow distribution among the routes. The complete absence of Monday traffic due to regional “sit-at-home” orders created a distinctive weekly pattern, with Tuesdays experiencing disproportionate congestion as the de facto first workday. Non-linear relationships between volume increases and congestion severity were observed, where modest volume changes produced amplified system-wide effects. Spatial analysis revealed that evening congestion disparities between distributors (14.9%) significantly exceeded morning differences (8.9%), indicating uneven network utilization. These findings illuminate how socio-political factors, activity patterns, and complex network dynamics shape urban mobility in rapidly developing contexts. This study offers empirical evidence supporting targeted interventions, including Tuesday-specific traffic management, evening-focused congestion mitigation strategies, and corridor-specific infrastructure improvements to enhance mobility in this representative mid-sized sub-Saharan city. Full article

Background: Cyclophosphamide (CP) chemotherapy is commonly associated with various side effects. The development of an effective therapy capable of counteracting these effects is of great interest. Objectives: We evaluated the effects of a novel polyherbal formulation (PHF) on CP cytotoxicity in TM3 cells and fictive ejaculation in rats, and determined its possible mechanism. Methods: The phytochemical analysis of PHF was determined by GC-MS. Various oxidative stress-related parameters (DPPH, ABTS⁺, CUPRAC, FRAP, MMP, and DCF-DA) and the cytotoxicity (hemolysis and HET-CAM) of PHF were evaluated. Its effect on fictive ejaculation was tested by recording the electromyographic activities of bulbospongiosus muscles, and the involvement of TRPV1/TRPM2 channels was investigated using their specific agonists and antagonists. Results: We found that PHF contained various phytocompounds. PHF prevented CP-induced oxidative stress in TM3 cells, probably due to its strong antioxidant potential. For instance, PHF inhibited apoptosis, lipid peroxidation, and ROS generation. Furthermore, the activities of capsaicin (CAP) and cumene hydroperoxide (CHPx) were significantly lowered by PHF, indicating TRPV1 and TRPM2 inhibition. In the in vivo study conducted in spinal male rats, the number of contractions of the bulbospongiosus muscles was significantly (p < 0.001) lowered in the PHF + DOPA (1.54 ± 0.3) and PHF + CAP (2.43 ± 0.74) groups, compared with the DOPA (8.75 ± 0.71) and CAP (7.41 ± 1.01) groups, respectively. Additionally, PHF delayed the pro-ejaculatory effects of dopamine (by 17.6%) and capsaicin (by 32.69%). The in silico study revealed a strong binding affinity between the selected PHF phytocompounds and the active pockets of TRPV1 and TRPM2. HET-CAM and hemolysis assays revealed no harmful effects of PHF. Conclusions: PHF prevented CP cytotoxicity in TM3 cells and delayed the pro-ejaculatory effects of dopamine and capsaicin in spinal rats through dopamine and TRPV1 inhibition. PHF could be a potential candidate for the management of CP chemotherapy-related disorders, such as premature ejaculation, in particular. Full article

A recent comprehensive pan-cancer study indicated the high translational potential of the transcript PHF19-207 as a biomarker for colon cancer. This study aimed to analyze the expression of PHF19-207 in colon tissue samples from two different settings to evaluate its clinical utility for diagnosis and screening. Surgical samples of colon tumor and non-tumor tissue were analyzed to determine the diagnostic value of PHF19-207 and its potential correlation with tumor characteristics. Additionally, biopsied samples from individuals undergoing national colorectal cancer screening were examined to assess the potential use of PHF19-207 in early detection. PHF19-207 expression levels were measured in all samples using Real-Time Polymerase Chain Reaction. A statistically significant difference was observed between tumor and non-tumor tissue (p = 0.002) and between tumor tissue and healthy mucosa samples (p < 0.001). Furthermore, polyp samples exhibited significantly higher PHF19-207 expression compared to healthy mucosa (p = 0.035). Receiver operating characteristic (ROC) analysis indicated that PHF19-207 can effectively differentiate malignant from healthy tissue, with an AUC value of 0.9044. Considering the increasing incidence of colorectal cancer in younger populations and the need for improved early detection, PHF19-207 expression could be explored as the basis for a relatively simple and efficient test, enabling a more comprehensive and affordable screening strategy. Full article

Background/Objectives: Finding single nucleotide polymorphisms (SNPs) and candidate genes that influence the expression of key traits is essential for genomic selection and helps improve the efficiency of poultry production. Here, we aimed to conduct a genome-wide association study (GWAS) for egg production traits in an F₂ resource population of chickens (Gallus gallus). Methods: The examined F₂ population was produced by crossing two divergently selected breeds with contrasting phenotypes for egg performance traits, namely Russian White (of higher egg production) and Cornish White (of lower egg production). Sampled birds (n = 142) were genotyped using the Illumina Chicken 60K SNP iSelect BeadChip. Results: In the course of the GWAS analysis, we were able to clarify significant associations with phenotypic traits of interest and economic value by using 47,432 SNPs after the genotype dataset was filtered. At the threshold p < 1.06 × 10⁻⁶, we found 23 prioritized candidate genes (PCGs) associated with egg weight at the age of 42–52 weeks (FGF14, GCK), duration of egg laying (CNTN4), egg laying cycle (SAMD12) and egg laying interval (PHF5A, AKR1B1, CALD1, ATP7B, PIK3R4, PTK2, PRKCE, FAT1, PCM1, CC2D2A, BMS1, SEMA6D, CDH13, SLIT3, ATP10B, ISCU, LRRC75A, LETM2, ANKRD24). Moreover, two SNPs were co-localized within the FGF14 gene. Conclusions: Based on our GWAS findings, the revealed SNPs and candidate genes can be used as genetic markers for egg weight and other performance characteristics in chickens to attain genetic enhancement in production and for further genomic selection. Full article

Background/Objectives: Periodontitis, a prevalent chronic inflammatory disease affecting tooth-supporting structures, has been increasingly linked to systemic conditions such as diabetes mellitus (DM) and cardiovascular diseases (CVDs). This study aimed to evaluate the periodontal status and levels of dipeptidyl peptidase-4 (DPP-4) and galectin-3 (Gal-3) in gingival crevicular fluid (GCF) of patients with periodontitis, heart failure (HF), and diabetes, exploring their potential as biomarkers for disease association. Methods: A cross-sectional study was conducted on 88 patients categorized into four groups: periodontally and systemically healthy (control, C); periodontitis (P); periodontitis and HF (P+HF); and periodontitis, HF, and diabetes (P+HF+D). Periodontal status was assessed using probing pocket depth (PPD) and Gingival Index (GI). GCF samples were collected and analyzed for DPP-4 and Gal-3 levels using ELISA. Statistical analyses were performed to assess differences between groups and potential correlations. Results: Results indicated significantly higher levels of DPP-4 in all test groups compared to controls (p < 0.0001), with the highest levels in the P+HF+D group. Similarly, Gal-3 levels were elevated in periodontitis patients, particularly in those with HF (p < 0.0001), and there was no significant difference between P+HF and P+HF+D groups. No significant differences were observed between smokers and non-smokers regarding these markers. Positive correlations were found between the periodontal parameters and the immunological markers in all test groups. Conclusions: The findings suggest that DPP-4 and Gal-3 may serve as potential biomarkers for periodontitis in association with heart failure and diabetes, with DPP-4 being more upregulated in the association with diabetes and Gal-3 with heart failure. Full article

Mild starvation due to low concentrations of an inhibitor of glycolysis, 2-deoxy-D-glucose, activates AMP-activated protein kinase (AMPK) and lysine-specific demethylase 2A (KDM2A) to reduce rRNA transcription and cell proliferation in breast cancer cells. However, the mechanisms of how AMPK regulates KDM2A are unknown. Here, we found that PHD finger protein 8 (PHF8) interacted with KDM2A and contributed to the reduction in rRNA transcription and cell proliferation by 2-deoxy-D-glucose in a breast cancer cell line, MCF-7. We analyzed how KDM2A bound PHF8 in detail and found that PHF8 interacted with KDM2A via two regions of KDM2A. One of the regions contained an intrinsically disordered region (IDR). IDRs can show rapidly switchable protein–protein interactions. Deletion of the PHF8-binding region activated KDM2A to reduce rRNA transcription, and 2-deoxy-D-glucose reduced the interaction between PHF8 and the KDM2A fragment containing the PHF8-binding region. A 2-deoxy-D-glucose or AMPK activator dephosphorylated KDM2A at Ser731, which is located on the N-terminal side of the PHF8-binding region. Replacement of Ser731 by Ala decreased binding of PHF8 to the KDM2A fragment that contains the PHF8-binding region and Ser731 and reduced rRNA transcription and cell proliferation. These results suggest that the mode of interaction between KDM2A and PHF8 is regulated via dephosphorylation of KDM2A through AMPK to control rRNA transcription, and control of the phosphorylation state of Ser731 would be a novel target for breast cancer therapy. Full article

Background/Objectives: This study aimed to demonstrate the safety and suitability of an infant formula manufactured from partially hydrolysed whey protein (PHF) compared to standard formula manufactured from intact cow’s milk proteins (IPF; whey–casein ratio, 60:40) in healthy term infants. Methods: This multicentre, randomised, double-blinded, placebo-controlled trial included infants of mothers who intended to exclusively formula feed. Infants ≤ 28 days of age received PHF or IPF for at least 90 and up to 180 days. A group of exclusively breastfed infants was included for reference. The safety evaluation consisted of an equivalence analysis of weight gain within +/−3 g/d after 90 days, further growth parameters, and adverse events. Results: Of the 249 infants randomised, 143 (76 IPF; 67 PHF), as well as 45 breastfed infants, completed the study per protocol. The mean difference in daily weight gain between the formula groups was within the equivalence margins (−2.4 g/d (95% CI 0.3–4.5)) with estimated means (SEM) of 34.9 (0.78) g/d (IPF) and 32.5 (0.76) g/d (PHF). No significant differences in weight gain, length, and head circumference or in the number, severity, or type of adverse events were observed. Comparable growth patterns were observed in the breastfed group. Conclusions: The PHF is safe and supports adequate infant growth with a daily weight gain non-inferior to a standard IPF. Full article

Aluminum alloy hot stamping technology has quickly become a research hotspot for many scholars due to its ability to solve key challenges such as poor formability, large rebound, and low dimensional accuracy of aluminum alloy sheets at room temperature. This work systematically reviews the progress of Hot-Forming-Quenching (HFQ^®) technology and its optimization processes. The effects of key forming parameters are summarized, including temperature, forming rate, friction, and crimping force on the forming properties of aluminum alloys. Additionally, an ontological model of thermal deformation behavior and damage evolution during hot forming is analyzed. A multifactorial strength prediction model, integrating grain size and reinforcement mechanisms, is highlighted for its ability to accurately predict post-forming yield strength. To address the limitations of HFQ^®, optimization methods for solid solution and aging heat-treatment stages are categorized and evaluated, along with their advantages and disadvantages. Furthermore, the latest advancements in two innovative hot stamping processes (Low-Temperature Hot Form and Quench (LT-HFQ^®) and pre-hardened hot forming (PHF)) are reviewed. LT-HFQ^® improves formability by pre-cooling the sheet while maintaining solution treatment, while PHF utilizes pre-hardened aluminum alloys, enabling brief heating, forming, and quenching to significantly reduce cycle time while ensuring component strength. Finally, by summarizing current technological progress and challenges, future directions for aluminum alloy hot stamping are outlined, including advancements in forming processes, material modeling, and optimization through multidisciplinary collaboration and artificial intelligence to drive further innovation. Full article