bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capivasertib augments chemotherapy via Akt inhibition in preclinical small cell lung cancer models
Authors: Long Cheng , Shen Hui , Li Hui , Han Lan 
Published: November 2024

AbstractBackgroundSmall cell lung cancer (SCLC) is a highly aggressive type of lung cancer for which platinum‐based chemotherapy is the standard of care. Despite an initial response to this therapy, patients eventually develop resistance to the chemotherapy.ObjectivesTo investigate the potential of capivasertib, an approved drug for advanced breast cancer, to enhance the efficacy of cisplatin in preclinical SCLC models and explore the underlying mechanisms.MethodsSCLC cell lines were treated with capivasertib and cisplatin, alone or in combination, to assess cell viability, proliferation, colony formation, and apoptosis. Next, capivasertib's effects, alone and combined with cisplatin, were evaluated in an SCLC mouse model. Mechanistic studies focused on Akt and MYC signaling, with constitutively active Akt overexpression used to assess its role.ResultsCapivasertib is active against a panel of SCLC cell lines regardless of cellular origin and genetic profiling with IC50 at a clinically achievable range. Particularly, capivasertib inhibits proliferation and anchorage‐independent colony formation and induces apoptosis in SCLC cells. It significantly augments cisplatin's inhibitory effects in all tested cell lines. Importantly, capivasertib at a non‐toxic dose is effective in delaying SCLC growth in mice and its combination with cisplatin achieves nearly complete tumor growth inhibition. Mechanistic studies confirm that capivasertib inhibits Akt and MYC signaling, and furthermore, that overexpression of constitutively active Akt reversed anti‐SCLC activity of capivasertib.ConclusionOur work is the first to reveal that Akt inhibition can augment chemotherapy in SCLC, and capivasertib is a useful addition to the treatment armamentarium for SCLC.
TNF‐alpha gene promoter's hypomethylation mediates a pro‐inflammatory phenotype in peripheral blood monocytes from apical periodontitis individuals
Authors: Fernández Alejandra , Bordagaray María José , Garrido Mauricio , Pellegrini Elizabeth , Baeza Mauricio , Chaparro Alejandra , Hernández Patricia , Hernández Marcela 
Published: November 2024

AbstractAimEpigenetic regulation of the key inflammatory genes plays a crucial role in controlling monocyte/macrophage‐mediated local and systemic responses to bacterial challenges. However, it has not been addressed in apical periodontitis (AP). We aimed to explore the methylation pattern of the TNF‐α gene promoter and its association with the inflammatory phenotype of peripheral blood monocytes from individuals with AP and controls.MethodsA cross‐sectional study was conducted, including otherwise healthy individuals with AP (n = 25) and controls (n = 29). Monocytes were isolated from the volunteer’s blood samples using a Ficoll gradient followed by negative immunoselection. RNA and DNA were extracted. The DNA methylation profiles of the TNF‐α gene promoter region were analyzed using bisulfite sequencing PCR. The mRNA expression levels of DNA methyltransferases 3a (DNMT3a) and Ten Eleven Translocation enzymes 1(TET1) were assessed by qPCR. A fraction of primary monocytes was also cultured for 24 h, and the supernatant was collected to measure cytokine levels through a Luminex assay. Generalized structural equation models (GSEM) evaluated the association between AP, DNA methylation, and TNF‐α protein expression controlled for potential covariates. Models included the effect of the methylation of TNF‐α gene promoter as a mediator of the association between AP and TNF‐α protein expression levels.ResultsMonocytes from AP individuals exhibited a heightened secretion of TNF‐α and IL‐1β and hypomethylation of the TNF gene promoter (p < .05). AP diagnosis was associated with the TNF‐α gene promoter´s hypomethylated profile and enhanced pro‐inflammatory cytokine levels, while lower methylation of the gene promoter region and ‐163 CpG single site mediated TNF‐α overexpression (p < .05).ConclusionsDNA hypomethylation at the TNF‐α gene mediates a proinflammatory phenotype in monocytes from AP patients, supporting a role in the systemic response.
Synthesis of ZrW2O8–ZrC composite powders by solid‐state exothermic oxidation reaction of ZrC and WO3 powders
Authors: Li Zhuorun , Wu Shoujun , Wang Jiajin , Zhang Xiaowen , Chen Yue 
Published: November 2024

AbstractIn this work, ZrW2O8‐coated ZrC composite powders are synthesized by solid‐state reaction method using ZrC and WO3 powders. Thermodynamic analysis shows that when the molar ratio of ZrC to WO3 is larger than 5:4, ZrW2O8 cannot be synthesized by solid reaction of ZrC and WO3. The favorable molar ratio of ZrC to WO3 for solid reaction synthesis ZrW2O8 is 1:2. After reacted below 800°C for 8 hours, only ZrC in the ZrC and WO3 mixture powders partially reacts with oxygen to form ZrO2. And there is no detectable reaction between WO3 and the formed ZrO2 to produce ZrW2O8. ZrC and WO3 can synthesize ZrW2O8 at 900°C. ZrW2O8‐coated ZrC composite powders can be synthesized using powder mixtures with molar ratio of ZrC:WO3 = 1:1.7 and ZrC:WO3 = 1:1.9 after heat treatment at 1000°C for 4 hours. The synthesized ZrW2O8‐coated ZrC particles show cubic shape with obvious particles growth. The exothermic oxidation reaction of ZrC leads to a significant increase in local temperature, which is believed to trigger partial reaction between ZrO2 and WO3 to form ZrW2O8.
Direct laser active brazing of 316Ti to alumina
Authors: Feng Jian , Herrmann Marion , Hurtado Antonio 
Published: November 2024

AbstractThis work addresses the challenges in brazing thermohydraulic sealings involving dissimilar materials, specifically 316Ti stainless steel and alumina, which have significantly different coefficients of thermal expansion (CTEs) and elastic constants. Traditional brazing methods require complex interlayers or extensive metallization steps, leading to issues such as dimensional changes, braze voids, and inadequate corrosion resistance due to prolonged high‐temperature exposure. A novel laser‐based brazing technique utilizing a diode laser is introduced to create high‐quality, localized joints while preserving the integrity of the parent materials. The study systematically optimizes laser process parameters using finite‐element modeling and the Taguchi method to achieve the desired bead geometry and thermal stress distribution with minimal heat input. Comparative analysis between laser active brazing (LAB) and conventional furnace brazing was conducted through metallography, shear testing, and autoclave testing. Results indicate that LAB parameters significantly affect bead thickness and shear strength, with laser‐brazed joints demonstrating superior quality and stability post‐autoclave testing compared with furnace‐brazed joints. The thermodynamic and kinetic aspects of the brazing process were also analyzed. In conclusion, the LAB method for brazing 316Ti to alumina proves to be a successful and efficient alternative, with joint properties meeting or exceeding those of traditional furnace brazing.
Unicentric Castleman Disease: Updates and Novel Insights Into Spindle Cell Proliferations and Aggressive Forms of a Localized Disease
Authors: Alnoor FNU , Rangel Alexandra , Luo Matthew , Silva Oscar , Chisholm Karen M. , O'Malley Dennis , Warnke Roger , Kumar Jyoti , Ohgami Robert S. 
Published: November 2024

ABSTRACTCastleman Disease (CD) is a rare lymphoproliferative disorder that can be separated into two primary forms: Unicentric Castleman disease (UCD) and multicentric Castleman disease (MCD). UCD is localized, while MCD is systemic. Though UCD generally has a favorable prognosis following surgical resection, more aggressive forms of this disease have been identified, including cases associated with dendritic and spindle cell proliferation. Genetic analysis has deepened our understanding of UCD. Despite advancements in better understanding the pathophysiology of UCD, challenges persist in the diagnosis, management, and treatment due to its rarity and heterogeneity. Here, we review current knowledge on UCD, highlighting the epidemiology, clinical presentation, diagnostic criteria, and treatment options while emphasizing the need for further research and innovation in therapeutic strategies.
Choose your own T‐cell fate: creation of a narrative‐based, decision‐making activity to engage students in immunology
Authors: Ritchie Helen E , Denyer Gareth , Webster Kylie E 
Published: November 2024

AbstractUndergraduate courses in immunology are content‐heavy and combined with a new, complex vocabulary, can be an overwhelming subject for students. In‐class active learning approaches have been found to improve understanding of difficult concepts in science, technology, engineering and mathematics (STEM) disciplines; however, many undergraduate courses maintain a high dependence on lecture‐style teaching because of time constraints, content demands and student resistance. We designed an online, out‐of‐class activity, the “Life and Death of a T cell”, to complement a lecture on a complex immunological concept, T‐cell development. Inspired by the “Choose Your Own Adventure” children's books, a fictional narrative was created in which students assume the role of a cell with a dream of becoming a helper T cell. Decision‐making scenarios then prompt students to draw on their knowledge from the lecture to successfully navigate the steps of T‐cell development. The activity was built on two platforms, Google Forms and H5P (HTML 5 Package), both of which are readily accessible and allow the inclusion of branching logic and the creation of a decision tree–based activity. An anonymous survey revealed that students found this interactive approach enjoyable, and their perceived understanding of the content significantly increased. Students appreciated the inclusion of a novel learning resource, with requests for similar activities to be developed for other immunological concepts. In conclusion, we developed a narrative‐based, decision‐making activity to complement a lecture on T‐cell development. As an out‐of‐class activity, this style of learning approach can potentially capitalize on the benefits of active learning, while also overcoming barriers of student resistance.
A geographic and social profile of Italy's great migration (1876–1913)
Authors: Fauri Francesca , Gasperoni Giancarlo 
Published: November 2024

AbstractThis article sheds light on Italian emigration flows with a focus on their geographical origins in the late 19th and early 20th centuries, that is, during the so‐called Great Migration. Annual province‐level data on Italian emigration are analysed in order to reconstruct the regional origins of emigrants, the factors motivating their decisions, their gender, and their literacy levels. The regions generating the largest population outflows were located in the North of the country. Despite the literature's focus on the Italian south diaspora to the US, the main destinations of Italian emigration in this period were other European countries. Explanations focusing on economic factors as emigration drivers prove weak. The provinces generating the greatest outflows do not appear to share any characteristics nor obey any underlying pattern: some tentative explanations concerning provinces of origin will be offered. Data relating to the emigration of women and children point to the central role of nuclear families, displaying a higher rate of growth compared to overall emigration, with peaks during the migration booms to Latin America (1890s) and the United States (1905–1907). No obvious connection emerges between emigrant outflow size and literacy levels: people migrated from the literate North as well as from the more impoverished regions featuring much lower literacy levels.
Social cohesion among Syrian and Turkish children, adolescents, and young adults in Turkey
Authors: Mittal Nitya , Parigi Marta , Vollmer Sebastian 
Published: November 2024

AbstractTurkey has received a large influx of Syrian refugees since the start of Syrian civil war in 2011. Integration and social cohesion have become important issues for public policy in Turkey. We study social cohesion among young Turkish nationals and Syrian refugees. Our study sample comprises of adolescents and young adults (12–30 years), and children (6–11 years) who participated in events of the “Education Program for Syrian Refugees and Host Communities” (BILSY) program conducted by the German Corporation for International Cooperation (GIZ). Social cohesion among adolescents and young adults is measured along three dimensions: sense of belonging, trust, and relational capacity. For children, we use behavioural games to measure two dimensions of social cohesion – altruism and trust. Our results show high social cohesion for both age groups, though lack of trust among Turkish nationals towards Syrian nationals is an area of concern. We also evaluate the impact of participation in BILSY program events using a randomised design and find that it had no impact on social cohesion. Our article adds to the limited literature on social cohesion among children and youths in countries affected by forced displacement.
A Qualitative Exploration of Healthcare Workers' Experiences of End of Life Care for People With an Intellectual Disability
Authors: McCarron Mary , Burke Eilish , Callion Philip Mc , Timmins Fiona 
Published: November 2024

ABSTRACTAimTo explore healthcare workers' experiences of end of life care for people with an intellectual disability.DesignA descriptive qualitative study.MethodSemi‐structured interviews were conducted with 28 healthcare workers who cared for older people with an intellectual disability at their end of life. Data were analysed using thematic analysis and reported according to the COREQ guidelines.ResultsThree major themes emerged: not joining up the dots, living the life desired in one's last days and dealing with death and beyond.ConclusionGaps emerged in the care of the person with intellectual disability. Pain assessment and pain management were particular challenges. End of life care was not always effectively planned, and earlier intervention, including end of life conversations, were needed. More needs to be done in terms of education for healthcare workers, and especially those in the acute care setting and palliative care services who may be unfamiliar with the needs of this cohort.Implications for the Profession and/or Patient CareThere is little consensus or understanding about the palliative care needs of those with intellectual disability. There are often specific challenges around providing palliative care particularly in relation to healthcare staffs' knowledge and confidence in understanding palliative care needs of this group and indeed communicating and assessing particular needs. Staff require educational preparation and training in palliative care to address the particular needs of this cohort.ImpactThis study revealed that there are gaps emerging in the care of the person with intellectual disability at the end of life. Pain assessment and pain management are particular challenges that require urgent attention.Patient or Public ContributionThere was no patient or publication contribution in this specific study, although IDS‐TILDA has a client representative and advisory committee that advise on all aspects of project design and management.
Efficacy of Olmesartan/Amlodipine Single‐Pill Combination on 24‐h Mean Systolic Blood Pressure Measured by Ambulatory Monitoring in Non‐Responders to Valsartan or Candesartan Monotherapy
Authors: Chung Woo‐Baek , Ihm Sang‐Hyun , Choi Yun‐Seok , Youn Ho‐Joong 
Published: November 2024

ABSTRACTThe aim of this study was to evaluate the efficacy of olmesartan/amlodipine (OLM/AML) single‐pill combination (SPC) therapy using ambulatory blood pressure monitoring (ABPM) in non‐responders to valsartan or candesartan monotherapy. Isolated systolic hypertension (ISH) is the most prevalent form of hypertension in middle‐aged and elderly individuals. Patients aged over 55 years who did not achieve the target systolic blood pressure (SBP < 140 mmHg) with valsartan 80 mg or candesartan 8 mg for at least 4 weeks were included. Doses were escalated from 20/5 mg to 40/5 mg and finally to 40/10 mg of OLM/AML SPC until patients reached the target SBP. Efficacy was assessed via ABPM by comparing baseline values with those in the 12th week. Office blood pressure (OBP) and brachial‐ankle pulse wave velocity (baPWV) were assessed at baseline, weeks 4, 8, and 12. Fifty‐four patients (average age 64 ± 6 years; 33 males) participated. The 24‐h mean BPs decreased significantly from an average of 146.2 ± 12.7/93.3 ± 9.2 mmHg to 129.7 ± 14.3/83.4 ± 10.7 mmHg (p < 0.001), and pulse pressures (PPs) from ABPM were reduced (p < 0.001). Additionally, significant reductions in night‐time SBP standard deviations (SDs) (14.7 ± 4.7 vs. 12.5 ± 3.9, p = 0.029) were observed at 12 weeks compared to baseline. OBPs significantly dropped from 151.1 ± 9.7/89.3 ± 8.3 mmHg to 125.5 ± 13.8/77.8 ± 8.8 mmHg after 12 weeks of SPC therapy (p < 0.001). Reductions in PPs of OBP and baPWVs were also observed. OLM/AML SPC therapy effectively reduced the 24‐h mean BP, as measured by ABPM, in hypertensive patients over 55 years old who failed to achieve a target SBP (< 140 mmHg) with angiotensin receptor blocker (ARB) monotherapy using valsartan 80 mg or candesartan 8 mg.Trial Registration: ClinicalTrials.gov identifier: NCT01713920
Evolution of hepatitis B virus polymerase and surface genes in patients receiving finite antiviral therapy
Authors: Chu Yu‐De , Hsu Chao‐Wei , Ho Pei‐Huan , Chiou Chih‐Yung , Lin Chih‐Lang , Liang Kung‐Hao , Lai Ming‐Wei , Yeh Chau‐Ting 
Published: November 2024

AbstractBackground and AimHepatitis B virus (HBV) reactivation could develop after withdrawal following a finite course of nucleoside analog (NA) therapy, leading to virological and clinical relapses. The genetic heterogeneity in the HBV surface and polymerase genes during finite NA therapy has not been carefully studied.MethodsSeven chronic HBV‐infected patients experiencing relapses following entecavir (ETV; n = 5; Patients 1 to 5) or tenofovir disoproxil fumarate (TDF; n = 2; Patients 6 and 7) withdrawal were included. Sera obtained before treatment and at relapses were retrieved and submitted for DNA extraction and amplicon‐specific deep sequencing.ResultsETV‐treated patients had a longer time‐to‐relapse than that of TDF‐treated patients (P = 0.0357). No drug‐resistance related polymerase mutation was detected during relapses, except for a low percentage (1.4%) of rtM204I mutation in Patient 1. Two surface truncation mutations (sW216*; 40.9% and sW182*; 4.7%) detected before treatment in two TDF‐treated patients (Patients 6 and 7, respectively) were overtaken by the wild types during subsequent drug‐withdrawal‐related relapses. The simultaneous presence of sG44E (T‐cell epitope) and sE164G (B‐cell epitope) mutations was associated with failure of HBV e antigen (HBeAg) seroclearance in ETV‐treated patients.ConclusionsIn conclusion, HBV genome continues to evolve during the courses of finite antiviral therapies. Pre‐existing surface truncation mutations can be overtaken by the wild types after relapses. The sG44E/sE164G mutations are associated with failure of HBeAg seroclearance.
Dietary assessments in individuals living with coeliac disease: key considerations
Authors: Lee Anne R. , Dennis Melinda , Lebovits Jessica , Welstead Lori , Verma Ritu , Therrien Amelie , Lebwohl Benjamin 
Published: November 2024

AbstractBackgroundCoeliac disease (CeD) is a type of enteropathy characterised by an immune‐mediated reaction to ingested gluten, resulting in impaired absorption of nutrients and symptoms such as bloating, abdominal cramping and diarrhoea. Currently, the only treatment for CeD is adherence to a gluten‐free diet (GFD). The latest draft guidance from the US Food and Drug Administration recommends that dietitians experienced in CeD management evaluate patients during the screening and treatment period of CeD clinical trials to assess adherence to a GFD. However, there are currently no standardised guidelines on dietary assessment of patients with CeD on a GFD and there is a lack of widespread availability of expertise in this field.MethodsBased on the findings of a literature review conducted between April and September 2023, this article provides an overview of key points to consider in the nutritional and dietary assessment of patients with CeD who are following a GFD, with particular focus on the clinical trial setting.ResultsBased on a consensus from dietitians and gastroenterologists experienced in treating patients with CeD, we present specific recommendations for registered dietitians who manage patients with CeD. We also describe the development of a simplified tool for assessment of adherence to a GFD, the Gluten‐Free Adherence Survey, based on these recommendations.ConclusionsThese guidelines cover nutritional and dietary assessment of patients with CeD, physical assessments, intake of oats, environmental considerations and the disease burden.
Elevated serum sodium is linked to increased amyloid‐dependent tau pathology, neurodegeneration, and cognitive impairment in Alzheimer's disease
Authors: Chen Yu‐Han , Wang Zhi‐Bo , Liu Xi‐Peng , Mao Zhi‐Qi ,   Alzheimer's Disease Neuroimaging Initiative
Published: November 2024

AbstractVascular dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD). While sodium is essential for maintaining vascular function, its role in AD pathology remains unclear. We included 353 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), assessing serum sodium levels, cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers, magnetic resonance imaging (MRI), and cognitive function. An independent sample (N = 471) with available CSF sodium‐related proteins and AD biomarkers was also included. Associations between serum sodium levels and AD pathology, neurodegeneration, and cognition were evaluated using linear regression models. Spearman's correlation analyses assessed the relationships between CSF sodium‐related proteins and AD biomarkers. Higher serum sodium levels were associated with increased AD pathology, reduced hippocampal volume, and greater cognitive decline (all p < 0.05). The relationship between serum sodium and amyloid PET was evident in several AD‐susceptible brain regions, including the neocortex and limbic system. Individuals with high serum sodium exhibited higher tau pathology, lower hippocampal volume, and more severe cognitive decline per unit increase in amyloid PET compared to those with low serum sodium (all p < 0.05). Among the 14 CSF sodium‐related proteins, which were inter‐correlated, six were significantly correlated with CSF AD pathology and amyloid PET, while two were correlated with hippocampal volume and cognitive function, with sodium channel subunit beta‐2 (SCN2B) and sodium channel subunit beta‐3 (SCN3B) showing the strongest correlations. These findings underscore the crucial role of serum sodium in AD progression, highlighting a potential network of sodium dysregulation involved in AD pathology. Targeting sodium may offer a novel therapeutic approach to slowing AD progression, particularly by impeding the progression of amyloid‐related downstream events.image