bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of porous medium on natural convection heat transfer in plume generated due to the combined effects of heat source and aligned magnetic field
Authors: Anwar Sahar , Ahmad Uzma , Rasool Ghulam , Ashraf Muhammad , Abbas Kamil
Published: July 2024

This study focuses on how the porous medium affects the plume generated due to line heat source when an aligned magnetic field is present. For this study, the momentum equation of the flow model is modified for porous medium by including the porosity term. A mathematical model is developed as coupled partial differential equations in order to study the flow problem. Later, a numerical solution is found for the system of coupled partial differential equations that are transmuted in to ordinary differential equations. For this purpose, the numerical characteristics of the problem are derived employing a shooting approach in combination with the built-in MATLAB tool bvp4c. The graphical illustrations of missing and specified boundary conditions demonstrate the impacts of porosity parameter [Formula: see text], magnetic force parameter S, Prandtl number [Formula: see text] and magnetic Prandtl number [Formula: see text] accompanied by a discussion of their corresponding physical implications. The novelty of this developed problem is proclaimed with justification by its emphasis on the principal characteristics of heat and fluid flow affected predominantly by the presence of a porous medium. The thorough examination of the porosity parameter [Formula: see text] for missing conditions depicts that the temperature and velocity profiles enhance while current density drops for the increasing values of the porosity parameter [Formula: see text]. Whereas, for specified conditions, the skin friction and magnetic flux enhance but heat transfer rate declines with increment in [Formula: see text].
New Insight Into Phytochromes: Connecting Structure to Function
Authors: Hughes Jon , Winkler Andreas
Published: July 2024

Red and far-red light–sensing phytochromes are widespread in nature, occurring in plants, algae, fungi, and prokaryotes. Despite at least a billion years of evolution, their photosensory modules remain structurally and functionally similar. Conversely, nature has found remarkably different ways of transmitting light signals from the photosensor to diverse physiological responses. We summarize key features of phytochrome structure and function and discuss how these are correlated, from how the bilin environment affects the chromophore to how light induces cellular signals. Recent advances in the structural characterization of bacterial and plant phytochromes have resulted in paradigm changes in phytochrome research that we discuss in the context of present-day knowledge. Finally, we highlight questions that remain to be answered and suggest some of the benefits of understanding phytochrome structure and function.
Functionalized Protein Binders in Developmental Biology
Authors: Schnider Sophie T. , Vigano M. Alessandra , Affolter Markus , Aguilar Gustavo
Published: July 2024

Developmental biology has greatly profited from genetic and reverse genetic approaches to indirectly studying protein function. More recently, nanobodies and other protein binders derived from different synthetic scaffolds have been used to directly dissect protein function. Protein binders have been fused to functional domains, such as to lead to protein degradation, relocalization, visualization, or posttranslational modification of the target protein upon binding. The use of such functionalized protein binders has allowed the study of the proteome during development in an unprecedented manner. In the coming years, the advent of the computational design of protein binders, together with further advances in scaffold engineering and synthetic biology, will fuel the development of novel protein binder–based technologies. Studying the proteome with increased precision will contribute to a better understanding of the immense molecular complexities hidden in each step along the way to generate form and function during development.
Data from Explore, Visualize, and Analyze Functional Cancer Proteomic Data Using the Cancer Proteome Atlas
Authors: Li Jun , Akbani Rehan , Zhao Wei , Lu Yiling , Weinstein John N. , Mills Gordon B. , Liang Han
Published: July 2024

Abstract
Reverse-phase protein arrays (RPPA) represent a powerful functional proteomic approach to elucidate cancer-related molecular mechanisms and to develop novel cancer therapies. To facilitate community-based investigation of the large-scale protein expression data generated by this platform, we have developed a user-friendly, open-access bioinformatic resource, The Cancer Proteome Atlas (TCPA, http://tcpaportal.org), which contains two separate web applications. The first one focuses on RPPA data of patient tumors, which contains >8,000 samples of 32 cancer types from The Cancer Genome Atlas and other independent patient cohorts. The second application focuses on the RPPA data of cancer cell lines and contains >650 independent cell lines across 19 lineages. Many of these cell lines have publicly available, high-quality DNA, RNA, and drug screening data. TCPA provides various analytic and visualization modules to help cancer researchers explore these datasets and generate testable hypotheses in an effective and intuitive manner. Cancer Res; 77(21); e51–54. ©2017 AACR.
Metabolic Dysfunction-Associated Steatotic Liver Disease in Severe Obesity and Concordance between Invasive (Biopsy) and Noninvasive (OWLiver®) Diagnoses
Authors: Navarro-Masip Èlia , Mestres Petit Nuria , Salinas-Roca Blanca , Herrerías Fernando , Vilardell Felip , de la Fuente Mari Cruz , Pallares Judit , Santamaría Maite , Zorzano-Martínez Marta , Sánchez Enric , Matías-Guiu Xavier , López-Cano Carolina , Soler Ana Gloria , León-Mengíbar Josep , Bueno Marta , Lecube Albert
Published: July 2024

Introduction: Nonalcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is an escalating health concern linked to obesity and type 2 diabetes. Despite liver biopsy being the gold standard, its invasiveness underscores the need for noninvasive diagnostic methods. Methods: A cross-sectional study was performed to assess MASLD using the noninvasive OWLiver® serum lipidomics test in a cohort of 117 patients with severe obesity undergoing bariatric surgery, comparing outcomes with liver biopsy. Exclusions (n = 24) included insufficient data, liver disease etiology other than MASLD, corticosteroid treatment, excessive alcohol consumption, low glomerular filtration rate, and declination to participate. Comprehensive laboratory tests, demographic assessments, and liver biopsies were performed. Serum metabolites were analyzed using OWLiver®, a serum lipidomic test that discriminates between healthy liver, steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and MASH with fibrosis ≥2 by means of three algorithms run sequentially. Results: Liver biopsy revealed a MASLD prevalence of 95.7%, with MASH present in 28.2% of cases. OWLiver® demonstrated a tendency to diagnose more severe cases. Body mass index (BMI), rather than the presence of type 2 diabetes, emerged as the sole independent factor linked to the probability of concordance. Therefore, the all-population concordance of 63.2% between OWLiver® and liver biopsy notably raised to 77.1% in patients with a BMI <40 kg/m2. These findings suggest a potential correlation between lower BMI and enhanced concordance between OWLiver® and biopsy. Conclusion: This study yields valuable insights into the concordance between liver biopsy and the noninvasive serum lipidomic test, OWLiver®, in severe obesity. OWLiver® demonstrated a tendency to amplify MASLD severity, with BMI values influencing concordance. Patients with BMI <40 kg/m2 may derive optimal benefits from this noninvasive diagnostic approach.
Acute Urticaria: Symptoms, Causes, and Evaluation of Phenotypes Prone to Chronicity
Authors: Gorgulu Akin Begum , Beyaz Sengul , Celebi Sozener Zeynep
Published: July 2024

Introduction: Urticaria is a condition that is characterized by the development of wheals (hives), angioedema, or both. If symptoms persist for less than 6 weeks, it is classified as acute urticaria (AU), and if they persist for longer than 6 weeks, it is classified as chronic urticaria (CU). Disease activity is evaluated using validated patient-reported outcome measures (PROMs) such as the 7-day urticaria activity score (UAS-7) and urticaria control test (UCT). In this study, we aimed to determine whether there was a difference between patients with chronic and recovered urticaria in terms of age, sex, symptoms, disease severity, disease control, and triggering factors by following patients with AU for 6 months. Methods: The routine tests were requested at the first admission of the patients. If previously examined, anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody, etc., were recorded. After the first examination, the patients were evaluated again using a visual analog scale (VAS), UCT, UAS-7, and medication scores (MSs) in the 1st, 3rd, and 6th months. Results: One hundred nine (F/M: 80/29) patients were included in the study. Twenty-seven patients had a previous history of AU, 22 of these patients were evaluated as having recurrent AU, and five became chronic during follow-up. Urticaria continued in 22 of 82 patients who presented with first-attack AU in the 3rd month and 17 in the 6th month. We had a chronicity rate of 24.7%. It was determined that having positive anti-TPO increased the risk of CU 1.69 times. A statistically significant improvement was found in the mean VAS, UCT, UAS-7, and MSs evaluated in the 1st, 3rd, and 6th months of patients with CU compared with baseline. Conclusion: AU is a common disease and usually heals in a short time without becoming chronic. Studies on the causes of chronicity are limited. Testing anti-TPO in patients presenting with AU may be useful in terms of disease course and risk of chronicity.
Abbreviation of Desensitization Protocol for Pediatric Patients with Lysosomal Storage Diseases Receiving Enzyme Replacement Therapy
Authors: Yörüsün Gökhan , Yilmaz Topal Özge , Şengül Emeksiz Zeynep , Küçükçongar Yavaş Aynur , Kasapkara Çiğdem Seher , Dibek Mısırlıoğlu Emine
Published: July 2024

Introduction: Lysosomal storage diseases (LSDs) constitute a group of metabolic disorders characterized by the accumulation of substrates within lysosomes. For their treatment, disease-specific enzyme replacement therapy (ERT) is employed. In cases of hypersensitivity reactions that may occur during these treatments, desensitization of enzyme therapy becomes necessary. Repeated desensitization procedures may result some degree of tolerance. This study presents cases of patients received abbreviated desensitization protocols following repeated desensitization procedures. Method: During the period between September 2019 and January 2024, pediatric patients who experienced anaphylactic reactions to ERT and whose desensitization protocols were abbreviated after receiving uneventful treatment with desensitization for at least a year were included in the study. Result: Six patients, four with Pompe disease, one with mucopolysaccharidosis type 2, and one with mucopolysaccharidosis type 4, had been receiving uninterrupted ERT by desensitization for at least 1 year. The mean age of the patients was 117.6 months (median: 104.5, IQR: 85.2–144). All patients experienced anaphylaxis as the initial reaction. Skin and intradermal tests were repeated on patients prior to protocol abbreviation. Premedication previously given to all patients was discontinued, and desensitization protocols were subsequently shortened by increasing the infusion rate and/or reducing the number of steps. Conclusion: The study investigated patients whose desensitization protocols were abbreviated. It demonstrated that some level of tolerance could be attained through repeated applications. This approach aims to identify concise, safe, and efficient protocols, thereby reducing hospitalizations, nosocomial infections, and treatment expenses.
Multiplex Intraoperative Rapid Immunohistochemistry with Noncontact Antibody Mixing for Distinguishing the Histologic Phenotype of Lung Cancer
Authors: Kuriyama Shoji , Imai Kazuhiro , Nanjo Hiroshi , Wakamatsu Yuki , Takashima Shinogu , Matsuo Tsubasa , Iwai Hidenobu , Demura Ryo , Suzuki Haruka , Harata Yuzu , Shibano Sumire , Wakita Akiyuki , Sato Yusuke , Nomura Kyoko , Minamiya Yoshihiro
Published: July 2024

Introduction: Determining a surgical strategy for early-stage lung cancer requires an accurate histologic diagnosis. Immunohistochemistry (IHC) enables reliable diagnosis of histological types but requires more time and more tumor tissue slides than hematoxylin and eosin staining. We aimed to assess the clinical validity of a new rapid multiplex IHC technique utilizing alternating current (AC) mixing for intraoperative lung cancer diagnosis. Methods: Forty-three patients who underwent radical resection of lung cancers were enrolled in a retrospective observational study. Frozen sections were prepared from lung tumor samples, and rapid IHC employing AC mixing was implemented alongside a multiplex IHC protocol targeting thyroid transcription factor-1 + cytokeratin 5, desmoglein 3 + Napsin A, and p63 + tripartite motif containing 29. We then evaluated the concordance between intraoperative diagnoses derived from rapid multiplex IHC and final pathology. Results: The concordance rate between the pathological diagnosis made with added rapid multiplex IHC and the final pathology was 93.0% (Cohen’s 𝜅 coefficient = 0.860 and 95% CI: 0.727–0.993). When considering only adenocarcinoma and squamous cell carcinoma, the diagnoses were in agreement for all cases. Conclusions: We suggest rapid multiplex IHC as a promising tool for determining surgical strategies for lung tumors.
Nail Disorders in Patients Living with HIV Coinfected with Monkeypox: A Clinical Study in 69 Mexican Cases
Authors: Sánchez-Cárdenas Carlos Daniel , Silva Flores Gustavo Antolín , Mendoza Ibarra Tania , Contreras Jimenez Laura , Guevara Castillo Rosa María , Pulido Díaz Nancy , Arenas Roberto G. , Moreno Coutiño Gabriela , Haneke Eckart
Published: July 2024

Introduction: Several infectious diseases can present nail manifestations, which may be useful for diagnosis and prognosis, and only a few reports have been made regarding monkeypox (mpox). The objective of this study was to describe the clinical characteristics of nail alterations in patients living with HIV coinfected with mpox. Methods: A prospective, cross-sectional study included patients living with HIV/AIDS, coinfected with mpox. We examined all 20 nails in search of nail plate alterations. Patients were divided into two groups, with and without nail disease, and the CD4 count was noted according to the Centers for Disease Control and Prevention (CDC) classification. A χ2 or Fisher’s exact test for qualitative variables and Mann-Whitney U and Kruskal-Wallis tests with post hoc Bonferroni test for quantitative variables were used to compare them. Data were analyzed with the SPSS Statistics 25 software. Results: Sixty-nine patients were included. The frequency of nail involvement was 58%. Papulonodular lesions were the most frequent type identified, with 21 cases (30.4%). A significant difference was observed between patients with nail disease versus median CD4 count (160 vs. 700/mm3; p = 0.002) and median HIV viral load (45,000 vs. 900/mL; p = 0.009). When comparing the characteristics of the nail lesions with the CDC Classification System for HIV infection by the CD4 count, a significant difference was observed in foot involvement, splinter hemorrhages, papulo-nodular lesions, anonychia, onychomadesis, acute paronychia, and nail bed ulcer-atrophy (p < 0.05). Conclusions: The frequency of nail lesions is high in patients living with HIV coinfected with mpox. In addition, they tend to be more destructive in patients with lower CD4 counts and higher viral loads.
Toward a Useful and Cost-Effective Workup in Chronic Polyneuropathy: The EXPRESS Study Protocol
Authors: Wiersma Madde , van der Star Gerjan M. , Eftimov Filip , van Eijk Ruben P.A. , Frederix Geert W.J. , van Doorn Pieter A. , Notermans Nicolette C. , Vrancken Alexander F.J.E.
Published: July 2024

Background: Knowledge gaps exist about the usefulness and extent of blood tests and nerve conduction studies in the workup of polyneuropathy. We hypothesize that a limited workup improves costs spent on diagnostics without loss of diagnostic reliability or disadvantageous effect on treatment choice in many patients with a clinical diagnosis of chronic polyneuropathy. We aim to determine which investigations are necessary in the workup of patients with suspected chronic polyneuropathy clinically diagnosed by neurologists in an outpatient clinic and will perform an early health technology assessment. Methods: This is a prospective multicenter quality in healthcare evaluation. We compare two diagnostic strategies, both performed on all participants: the standard care by each patient’s neurologist and the proposed (limited) workup by the study panel members consisting of neurologists with experience in neuromuscular diseases. Results: The primary outcome is the effectiveness of a limited workup expressed as concordance between the patient’s neurologist diagnosis and the panel diagnosis. This will be related to differences in costs and impact on treatment or patient management otherwise. Other outcomes are burden/gain for the patient in terms of number of investigations, time to diagnosis, hospital visits, sick leave, loss of productivity, expenses, experienced quality of care. Conclusion: This multicenter prospective observational study on quality in health care will provide improved evidence about the components of a cost-effective workup for patients with chronic polyneuropathy.
Analysis of Neuropeptides in the Intestinal Mucus of Patients with Ulcerative Colitis Using RNA Sequencing
Authors: Nakamura Masanao , Murate Kentaro , Maeda Keiko , Yamamura Takeshi , Sawada Tsunaki , Ishikawa Eri , Furukawa Kazuhiro , Hirose Takashi , Uetsuki Kota , Iida Tadashi , Mizutani Yasuyuki , Yamao Kentaro , Ishizu Yoji , Ishikawa Takuya , Honda Takashi , Kawashima Hiroki
Published: July 2024

Introduction: Inflammation in ulcerative colitis (UC) originates in the colorectal mucosa. Transcriptome sequencing analysis of the colorectal mucosa allows the identification of potential neuropeptides related to local neurotransmission. The intestinal mucus lining the surface of the mucosa may harbor biomarkers of mucosal inflammation; however, this has not been sufficiently investigated, given the difficulty in obtaining human samples. We previously reported the feasibility of obtaining mucin samples for proteomic analysis by brushing during colonoscopy. Herein, we aimed to investigate the composition of the intestinal mucus and detect neuropeptides characteristic of UC. Methods: Mucus and mucosal samples were collected from patients with UC from the colorectum in areas showing remission or active UC using a brush catheter and biopsy forceps during colonoscopy. RNA sequencing findings of mucus samples of active and remission areas were compared. RNA and protein expression levels of significantly upregulated neuropeptides were analyzed. Results: Of the neuropeptides associated with UC, somatostatin (SST) was significantly elevated in areas of remission, according to RNA sequencing results of mucus and expression levels in mucus RNA and proteins. Conversely, SST expression in the mucosa was increased in the inflamed areas. Flow cytometry revealed that the fluorescence intensity of SST-positive cells in the remission zone was higher in the mucus than in the mucosa. Conclusion: SST expression in the mucus is considered to be an important factor associated with UC activity.
IGF1 Haploinsufficiency: Phenotype and Response to Growth Hormone Treatment in 9 Patients
Authors: Punt Lauren D. , van der Kaay Daniëlle C.M. , van Setten Petra A. , de Groote Kirsten , Kruijsen Anne R. , Bocca Gianni , de Munnik Sonja A. , Renes Judith S. , de Bruin Christiaan , Losekoot Monique , van Duyvenvoorde Hermine A. , Wit Jan M. , Joustra Sjoerd D.
Published: July 2024

Introduction: The clinical features of bi-allelic IGF1 defects are well established, i.e., severe growth failure and microcephaly, delayed psychomotor development, and sensorineural deafness. However, information on clinical and endocrine consequences of heterozygous IGF1 variants and treatment options is scarce. We aimed at extending the knowledge base of the clinical presentation and growth response to recombinant human growth hormone (rhGH) of patients carrying such variants. Methods: Retrospective case series of patients with pathogenic heterozygous IGF1 variants. Results: Nine patients from six families were included, harbouring five whole or partial gene deletions and one frameshift variant resulting in a premature stop codon (three de novo, one unknown inheritance). In the other two families, variants segregated with short stature. Mean (SD) birth length was −1.9 (1.3) SDS (n = 7), height −3.8 (0.6) SDS, head circumference −2.5 (0.6) SDS, serum IGF-I −1.9 (0.7) SDS, serum IGFBP-3 1.1 (0.4) SDS (n = 7), and GH peak range 5–31 μg/L (n = 4). Five patients showed feeding problems in infancy. Average height increased after 1 and 2 years of rhGH treatment by 0.8 SDS (range 0.3–1.3 SDS) and 1.3 SDS (range 0.5–2.0 SDS), respectively. Adult height in 2 patients was −2.8 and −1.3 SDS, which was, respectively, 1.3 and 2.9 SDS taller than predicted before start of treatment. Conclusion: Haploinsufficiency of IGF1 causes a variable phenotype of prenatal and postnatal growth failure, microcephaly, feeding difficulties, low/low-normal serum IGF-I values in contrast to serum IGFBP-3 in the upper-normal range. Treatment with rhGH increased growth in the first 2 years of treatment, and in 2 patients adult height after treatment was higher than predicted at treatment initiation.
The Efficacy and Safety of Retrograde Intrarenal Surgery in Elderly Patients: A Propensity Score Matching Study by the RIRSearch Group
Authors: Akgül Murat , Özcan Ridvan , Yazıcı Cenk , Başataç Cem , Özman Oktay , Sıddıkoğlu Duygu , Çınar Önder , Çakır Hakan , Şahin Mehmet Fatih , Sancak Eyüp Burak , Başeskioğlu Barbaros , Elmaağaç Burak , Önal Bülent , Akpınar Haluk
Published: July 2024

Introduction: The aim of the study was to evaluate the efficacy and safety of retrograde intrarenal surgery (RIRS) in elderly patients by comparing them with propensity score-matched age-groups. Methods: Patients who underwent RIRS to treat upper urinary tract stone disease at seven centers were included in the study and were divided into four groups. The age intervals of the patients in group 1, group 2, group 3, and group 4 were 18–29 years old, 30–49 years old, 50–64 years old, and over 65 years old, respectively. Propensity score matching analysis was used to homogenize the groups in terms of demographic and clinical properties. Operative results, preoperative complications, perioperative complications, postoperative complications, duration of hospitalization time, and stone-free status were compared between groups. Results: A total of 1,017 patients were included in the study. There were 69 (9.9%) patients in group 1, 324 (46.5%) in group 2, 217 (31.1%) in group 3, and 87 (12.5%) in group 4 after propensity score matching. The operation time and postoperative complication rates were significantly different among groups, whereas the hospitalization time, perioperative complication rates, and stone-free status were similar. The operation time was significantly higher in patients over 65 years old (p = 0.001). The postoperative complication rates were significantly higher in group 1 with Clavien I-II complication predominance (p = 0.003). Conclusion: The efficacy and safety of RIRS did not change with aging, and RIRS was an effective option for the treatment of upper urinary system stones in elderly patients.
Dendritic Morphology of Developing Hippocampal Neurons in Cyp11a1 Null Mice
Authors: Jiang Hao-Hua , Wu Tzu-Hsuan , Lee Li-Jen , Lee Jui-Chen , Chung Bon-chu , Yang Feng-Ming , Hu Meng-Chun
Published: July 2024

Introduction: Neurosteroids have a variety of neurological functions, such as neurite growth, neuroprotection, myelination, and neurogenesis. P450scc, encoded by CYP11A1 gene, is the cholesterol side chain cleavage enzyme that catalyzes the first and rate-limiting step in steroidogenesis. In this study, we examine the dendritic morphology in developing hippocampal neurons of Cyp11a1 null mice at P15, a critical period for synapse formation and maturation. Methods: Knockout mice were maintained until P15 with hormone administration. The Golgi-Cox method stained CA1 and CA3 pyramidal neurons in the hippocampus to reveal dendritic morphology. Results: We demonstrated that Cyp11a1 null mice usually die within 7 days after birth and thus collected brain samples at postnatal day 5 (P5) for examination. There was significant shrinkage of dendrite size and diminishment of dendritic branching in CA1 and CA3 pyramidal neurons in the hippocampus of Cyp11a1 null mice, suggesting a developmental delay. We wonder if this delay may catch up later in life. Since the age of P15 is a critical period for synapse formation and maturation, the Cyp11a1 null mice were rescued by receiving hormone administration until P15 that the dendritic morphology in the developing hippocampal neurons could be examined. The results indicated that the total dendritic length, the number of dendritic branches, as well as dendritic arborization in the CA1 and CA3 pyramidal neurons are significantly decreased in P15 knockout mice when compared to the wild type. The spine densities were also significantly decreased. In addition, the Western blot analysis revealed decreased PSD-95 expression levels in the knockout mice compared to the wild type at P15. Conclusion: These results suggested that Cyp11a1 deficiency impairs the dendritic structures in the developing hippocampal pyramidal neurons.
Safety Profile of Lipid Emulsion in Clinical Practice: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System
Authors: Okada Akira , Sera Shoji , Takeda Koki , Nagai Naomi
Published: July 2024

Introduction: Lipid emulsion preparations, known for their clinical utility, are associated with various adverse events related to lipid metabolism. In this study, we analyzed the safety profile of lipid emulsions in clinical practice, using a real-world database. Methods: The US Food and Drug Administration Adverse Event Reporting System database was used to retrieve adverse events associated with lipid emulsion use. The risk of adverse events was evaluated based on the reported odds ratio and time-to-onset analysis. Results: A total of 4,430 relevant adverse event reports were identified. Hepatic dysfunction tended to occur in the early stages after administration, regardless of the lipid emulsion type. The incidence of hepatic dysfunction varies depending on the triglyceride content of the administered lipid emulsion. Infection tended to occur in the early stages of lipid emulsion administration; however, the incidence did not significantly differ depending on triglyceride content. Conclusion: Our study revealed adverse lipid emulsion events, indicating the need for comprehensive safety management, particularly in the early stages, for clinical use. Particularly, patients receiving parenteral nutrition, irrespective of lipid emulsion administration, necessitate thorough monitoring of liver function and triglyceride levels and reassessment of infusion rates.
NLRP3 Expression and Its Predictive Role in Heart Failure with Preserved Ejection Fraction among Non-Valvular Atrial Fibrillation Patients
Authors: Chen Shijian , Yu Ziheng , Wen Wen , Chen Jiming , Lu Kongjie
Published: July 2024

Introduction: The aim of this study was to investigate the expression and predictive value of NOD-like receptor thermal protein domain-related protein 3 (NLRP3) in patients with non-valvular atrial fibrillation (NVAF) with heart failure with preserved ejection fraction (HFpEF). Methods: This was a retrospective analysis of 121 patients diagnosed with NVAF. According to the occurrence of HFpEF, 81 patients were assigned to the NVAF group and 40 patients to the NVAF/HFpEF group. The levels of NLRP3, B natriuretic peptide (BNP), and interleukin-1β (IL-1β) were determined using ELISA. Independent predictors for HFpEF in NVAF were determined using logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of each factor. Results: Expression levels of NLRP3, BNP, and IL-1β in the NVAF/HFpEF group, as well as the H2FPEF score were significantly higher than those in the NVAF group. Pearson analysis showed that NLRP3, BNP, and IL-1β expression levels in NVAF patients and the H2FPEF score was positively correlated (r = 0.409, r = 0.244, r = 0.299, p < 0.001). Multivariate logistic regression analysis showed that the NLRP3, BNP, or H2FPEF score can be used as independent factor for predicting the occurrence of HFpEF in NVAF. ROC curves showed that the areas under the curve of NLRP3, BNP, and H2FPEF scores for predicting the occurrence of HFpEF in NVAF patients were 0.856, 0.831, and 0.811, respectively. Conclusion: The NLRP3 level is elevated in the peripheral blood of NVAF patients with HFpEF and is positively correlated with the H2FPEF score. NLRP3 may serve as a potential predictor of HFpEF in patients with NVAF.
A Randomized Trial of the Impact of Ferric Citrate on Erythropoietin and Intravenous Iron Use in Patients Receiving Dialysis
Authors: Block Geoffrey A. , Mizani Mohammed Reza , Broumand Varshasb , Newby F. David , Erinle Ayodele , Arias Carolina , Block Martha , Brillhart Stephanie , Leppink Amanda , Danese Mark , Dittrich Mary
Published: July 2024

Introduction: Ferric citrate (FC) is an FDA-approved iron-based phosphate binder for adults with dialysis-dependent chronic kidney disease. This study investigated the impact of FC as the primary phosphate-lowering therapy on utilization of erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron. Methods: In this randomized, open-label, active-controlled, multicenter study (NCT04922645), patients on dialysis and receiving ESAs were randomized to receive FC or remain on standard of care (SOC) phosphate-lowering therapy for up to 6 months. Primary endpoints were the difference in change from baseline to efficacy evaluation period (EEP) in mean monthly ESA and IV iron doses. Secondary endpoints included treatment differences in hemoglobin, phosphate, TSAT, and ferritin levels. Results: Two hundred nine patients were randomized to FC and had a day 1 dosing visit (n = 103) or SOC (n = 106). The two groups had similar baseline laboratory characteristics; however, atherosclerotic CV disease, peripheral vascular disease, and congestive heart failure were more common in the SOC group. The mean treatment difference in ESA monthly dose was −30.8 μg (FC vs. SOC; p = 0.02). An absolute though non-statistically significant change in mean monthly IV iron dose of −37.2 mg (p = 0.17) was observed with FC. Mean hemoglobin, TSAT, and ferritin all increased from baseline to the EEP with FC versus SOC. Serious adverse events occurred in 28% of patients receiving FC versus 37% in those receiving SOC. Conclusions: In patients receiving dialysis, treatment with FC as compared to remaining on SOC phosphate binders resulted in reductions in mean monthly ESA and IV iron dose.
Factor VIII Levels and ISTH Disseminated Intravascular Coagulation Scores Do Not Distinguish Disseminated Intravascular Coagulation from the Coagulopathy of Liver Disease
Authors: Allen Cecily , Heskel Marina , Butt Ayesha , Tormey Christopher , Pine Alexander B. , Lee Alfred I. , Gautam Samir
Published: July 2024

Introduction: Distinguishing disseminated intravascular coagulation (DIC) from the coagulopathy of liver disease represents a common clinical challenge. Here, we evaluated the utility of two diagnostic tools frequently used to differentiate between these conditions: factor VIII (FVIII) levels and the International Society on Thrombosis and Hemostasis (ISTH) DIC score. Methods: To this end, we conducted a retrospective chart review of patients with DIC, liver disease, or both. Multiple logistic regression was performed, and receiver operating characteristic curves were generated to calculate the area under curve (AUC) for distinguishing DIC in the setting of liver disease. Results: Among 123 patients with DIC, liver disease, or liver disease plus DIC, FVIII levels did not differ significantly. ISTH scores were lower in patients with DIC than in liver disease with or without DIC. Addition of several laboratory parameters to the ISTH score, including mean platelet volume, FV, FVIII, international normalized ratio, and activated partial thromboplastin time, improved AUC for distinguishing DIC in liver disease from liver disease alone (AUC = 0.76; p < 0.0001). Conclusion: We conclude that FVIII levels do not distinguish DIC from liver disease, and ISTH DIC scores are not predictive of DIC in patients with liver disease. Inclusion of additional lab variables within the ISTH DIC score may aid in identifying DIC in patients with liver disease.
A Comparison of the Anticoagulation Efficacy and Safety of Epoprostenol to Heparin and Citrate in Children Receiving Continuous Renal Replacement Therapy
Authors: Sondhi Esha , Stewart Martha , Harper Jenna , Konyk Leslie , McSteen Coleen , Crowley Kelli L. , Kim-Campbell Nahmah , Fabio Anthony , Fuhrman Dana Y.
Published: July 2024

Introduction: Anticoagulants are used in continuous renal replacement therapy (CRRT) to prolong filter life. There are no prior investigations directly comparing epoprostenol to more commonly used forms of anticoagulation in children. Therefore, the primary aim of this study was to assess the efficacy and safety of epoprostenol as compared to heparin and citrate anticoagulation in a pediatric cohort. Methods: We performed a retrospective analysis of all patients <18 years of age admitted to an academic quaternary care children’s hospital from 2017–2022 who received epoprostenol, heparin, or citrate exclusively for CRRT anticoagulation. Efficacy was evaluated by comparing the hours to the first unintended filter change and the ratio of filters used to CRRT days. Safety was assessed by evaluating changes in platelet count and vasoactive-ionotropic score (VIS). Results: Of 101 patients, 44 received epoprostenol (43.6%), 38 received heparin (37.6%), and 19 received citrate (18.8%). The first filter change was more commonly planned in patients receiving anticoagulation with epoprostenol (43%) as compared to citrate (11%) or heparin (29%) (p = 0.034). Of those patients where the first filter change was unintended (n = 33), there were greater median hours until the filter was replaced in those receiving epoprostenol (29) when compared to citrate (21) (p = 0.002) or heparin (18) (p = 0.003). There was a smaller median ratio of filters used to days on therapy in the patients that received epoprostenol (0.53) when compared to citrate (1) (p = 0.003) or heparin (0.75) (p = 0.001). For those receiving epoprostenol, there was no significant decrease in platelet count when comparing values prior to CRRT initiation through 7 days of therapy. There was no significant difference in VIS when comparing values prior to CRRT initiation through the first 2 days of CRRT. Conclusions: Epoprostenol-based anticoagulation is effective when compared to other anticoagulation strategies used in pediatric CRRT with a favorable side effect profile.
Factors Affecting Recurrence and Survival in Stage IIA Colon Cancer Patients
Authors: Erciyestepe Mert , Selvi Oğuzhan , Dinç Gülhan , Öztürk Ahmet Emin , Aydın Okan , Dinç Sonuşen Şermin , Güneş Tuğçe Kübra , Avcı Tugay , Vatansever Sezai , Çelik Emir , Atcı Muhammed Mustafa
Published: July 2024

Introduction: Our study delves into the intricate interplay of risk factors and the strategic selection of adjuvant therapy, scrutinizing their influence on recurrence and survival outcomes in stage IIA (T3N0M0) colon cancer patients. Materials and Methods: The study examined the medical records of patients who underwent surgery for stage IIA colon cancer. Identification of stage IIA (pT3N0M0) colon cancer involved a comprehensive review of postoperative clinical records and histological reports. Parameters such as demographic data, tumor characteristics, microsatellite instability status, tumor locations, recurrence risk factors, preoperative carcinoembryonic antigen levels, and adjuvant treatments were systematically evaluated. Results: In our study involving 220 patients, 138 were male (62.7%), with a median age of 62 years and a median body mass index of 25.1 kg/m2. In the patient group without risk factors, no statistically significant difference was detected in disease-free survival (DFS) rates between those who received treatment and those who did not (p = 0.546). DFS rates of patients with >1 risk factor were statistically significantly lower than those with a single risk factor (p = 0.017). In patients with >1 risk factor, the DFS of those who did not receive adjuvant treatment was significantly lower than those who received adjuvant treatment (p < 0.001). In the patient group with recurrence, when adjuvant treatments were considered, recurrence was significantly higher in the group receiving capecitabine (p = 0.01). Conclusion: The decision for adjuvant chemotherapy in stage IIA colon cancer patients involves careful consideration of various parameters and risk factors. The evolving landscape of research may refine recommendations, ensuring optimal treatment outcomes while minimizing unnecessary toxicity.
Artificial Intelligence-Driven Prediction Revealed CFTR Associated with Therapy Outcome of Breast Cancer: A Feasibility Study
Authors: Kováčová Mária , Hlaváč Viktor , Koževnikovová Renata , Rauš Karel , Gatěk Jiří , Souček Pavel
Published: July 2024

Introduction: In silico tools capable of predicting the functional consequences of genomic differences between individuals, many of which are AI-driven, have been the most effective over the past two decades for non-synonymous single nucleotide variants (nsSNVs). When appropriately selected for the purpose of the study, a high predictive performance can be expected. In this feasibility study, we investigate the distribution of nsSNVs with an allele frequency below 5%. To classify the putative functional consequence, a tier-based filtration led by AI-driven predictors and scoring system was implemented to the overall decision-making process, resulting in a list of prioritised genes. Methods: The study has been conducted on breast cancer patients of homogeneous ethnicity. Germline rare variants have been sequenced in genes that influence pharmacokinetic parameters of anticancer drugs or molecular signalling pathways in cancer. After AI-driven functional pathogenicity classification and data mining in pharmacogenomic (PGx) databases, variants were collapsed to the gene level and ranked according to their putative deleterious role. Results: In breast cancer patients, seven of the twelve genes prioritised based on the predictions were found to be associated with response to oncotherapy, histological grade, and tumour subtype. Most importantly, we showed that the group of patients with at least one rare nsSNVs in cystic fibrosis transmembrane conductance regulator (CFTR) had significantly reduced disease-free (log rank, p = 0.002) and overall survival (log rank, p = 0.006). Conclusion: AI-driven in silico analysis with PGx data mining provided an effective approach navigating for functional consequences across germline genetic background, which can be easily integrated into the overall decision-making process for future studies. The study revealed a statistically significant association with numerous clinicopathological parameters, including treatment response. Our study indicates that CFTR may be involved in the processes influencing the effectiveness of oncotherapy or in the malignant progression of the disease itself.
Illness Trajectories After Revascularization in Patients With Peripheral Artery Disease: A Unified Approach to Understanding the Risk of Major Amputation and Death
Authors: Li Qiuju , Birmpili Panagiota , Atkins Eleanor , Johal Amundeep S. , Waton Sam , Williams Robin , Boyle Jonathan R. , Harkin Denis W. , Pherwani Arun D. , Cromwell David A.
Published: July 2024

BACKGROUND:

The aim of this study was to investigate the illness trajectories of patients with peripheral artery disease (PAD) after revascularization and estimate the independent risks of major amputation and death (from any cause) and their interaction.

METHODS:

Data from Hospital Episode Statistics Admitted Patient Care were used to identify patients (≥50 years of age) who underwent lower limb revascularization for PAD in England from April 2013 to March 2020. A Markov illness–death model was developed to describe patterns of survival after the initial lower limb revascularization, if and when patients experienced major amputation, and survival after amputation. The model was also used to investigate the association between patient characteristics and these illness trajectories. We also analyzed the relative contribution of deaths after amputation to overall mortality and how the risk of mortality after amputation was related to the time from the index revascularization to amputation.

RESULTS:

The study analyzed 94 690 patients undergoing lower limb revascularization for PAD from 2013 to 2020. The majority were men (65.6%), and the median age was 72 years (interquartile range, 64–79). One-third (34.8%) of patients had nonelective revascularization, whereas others had elective procedures. For nonelective patients, the amputation rate was 15.2% (95% CI, 14.4–16.0) and 19.9% (19.0–20.8) at 1 and 5 years after revascularization, respectively. For elective patients, the corresponding amputation rate was 2.7% (95% CI, 2.4–3.1) and 5.3% (4.9–5.8). Overall, the risk of major amputation was higher among patients who were younger, had tissue loss, diabetes, greater frailty, nonelective revascularization, and more distal procedures. The mortality rate at 5 years after revascularization was 64.3% (95% CI, 63.2–65.5) for nonelective patients and 33.0% (32.0–34.1) for elective patients. After major amputation, patients were at an increased risk of mortality if they underwent major amputation within 6 months after the index revascularization.

CONCLUSIONS:

The illness–death model provides an integrated framework to understand patient outcomes after lower limb revascularization for PAD. Although mortality increased with age, the study highlights patients <60 years of age were at increased risk of major amputation, particularly after nonelective revascularization.
Situational aspects of mental regulation of psychic states
Authors: Prokhorov Aleksander O.
Published: July 2024

Background. The study of psychological mechanisms and patterns of "conscious" regulation of psychic states turns us to the structures of consciousness and their functions in the regulatory process. These structures and mechanisms remain the least studied to date, while the need to understand the psychological mechanisms of self-regulation of states is extremely relevant, and knowledge about them is in demand in various situations of a subject’s life. Objective. The presented analytical article analyzes the concept of "situation" (approaches, principles, structure, levels, etc.) considered as a "psychological situation" and investigates its role in the actualization of the mental regulation of psychic states. Results. It is shown that psychological situation, through the formation of an impression, which is a cognitive-affective complex, “launches” the regulatory process, actualizing the structures of consciousness constituted by semantic, reflective, representative structures, experiences, and the Self system. The article provides an analysis of results of the situational conditioning of self-regulation of states among the employees of government institutions, in the process of teaching students, in difficult life situations (reversible and irreversible) as well as its impact on the activation of consciousness structures and, accordingly, on the operational means of regulation. Consideration is also given to the relationships between mental structures in the process of regulating the subject's states. Conclusion. The formation of functional structures "situation - mental structures - regulatory means - mental states" occurs in the process of psychic states regulation. The actualization of functional structures is due to the purpose of regulation - the need to change the state in accordance with requirements of the situation of the subject's life activity. Activation of the consciousness structures mediating the choice of operational means of regulation and their use leads to a change in the psychic state.
Friendship as a factor of transformation of self-regulatory processes of personality
Authors: Ryabikina Zinaida I. , Vasilchenko Natalia A.
Published: July 2024

Background. In the face of threats of increased individualism and the prevalence of loneliness problems, supporting the individual’s focus on the values of friendly relationships and focusing research on understanding the transformation processes of the individual (in particular, changes in the self-regulation characteristics) in the context of his co-existence with a significant Other is a relevant and little-studied topic. Purpose. The study had its purpose to identify the specifics of changes in the processes of self-regulation of an individual under conditions of coexistence with a friend. Methods. “Self-regulation Profile Questionnaire by V.I. Morosanova (SRPQM)” and its modification, methodology for studying personality self-esteem by S.A. Budassi and its modification. Sample. The study involved students of Kuban State University from different areas of training (N = 100). Results. The study revealed significant changes in the students’ general level of self-regulation and its characteristics depending on existing friendships: an increase in behavior conscious self-regulation (“general level” scale), optimization of conditions in achieving one’s goals (“modeling” scale) based on a critical attitude to the performing actions (“result evaluation” scale), an increase in plasticity of the regulatory processes (“flexibility” scale). Conclusions. In a situation of co-existence, a “possible Other” can be both a destructive factor for a person’s self-regulation (impaired planning, value disorientation, etc.), as well as a supporting factor, providing more accurate self-identification, certainty in setting goals, increasing agency in organizing the spaces of one’s being. Friendship relationships, being a person’s coexistence with a “significant Other”, generally increase the resources of self-regulation: the modeling process is optimized, flexibility and adequacy in evaluating results increase. At the same time, a person’s independence decreases, which is natural, since another subject is involved in the regulatory process.