bluuebunny/crossref_metadata_2025 huggingface dataset:
How ultrasonication treatment drives the interplay between lysinoalanine inhibition and conformational performances: A case study on alkali‐extracted rice residue protein isolate
Authors: Liu Jiarui , Wang Yang , Shi Wangbin , Meng Xiangren , Mintah Benjamin Kumah , Dabbour Mokhtar , Zhang Zhaoli , He Ronghai , Ma Haile
Published: November 2024

Lysinoalanine (LAL) formed during alkaline extraction of rice residue protein (RRPI), which limited its application in the food industry. In this study, the influence of ultrasonication parameters (acoustic power density, ultrasound duration, and ultrasound temperature) on the inhibition of LAL formation and conformational attributes of RRPI during alkaline extraction was elucidated. The results suggested that the acoustic power density substantially modified the chemical interaction forces between RRPI molecules. At a power density of 60 W/L, the ionic bonds (14.37%) and hydrophobic interactions (49.28%) reached the maximum, while hydrogen bonds (15.29%) and disulfide bonds (21.06%) reached the minimum. Moreover, acoustic power density at 60 W/L caused a decrease of 18.02% and 12.2% in α‐helix, and β‐turn, respectively, shifting toward β‐sheet, random coil, with an increase of 7.31% and 36.16%. Following ultrasonication, the protein particle size distribution curve shifted in the direction of smaller particle size, forming a relatively concentrated and uniform protein distribution. Sonication power, temperature, and time decreased the absolute value of Zeta potential. Furthermore, significant destruction in microstructure was elicited by sonication, which made the structure looser and more microparticles. Pearson correlation analysis suggested that the inhibition in the levels of LAL was most influenced by the increase of sulfhydryl groups and Zeta potential, as well as the reduction of α‐helix content, in which the alteration of the total sulfhydryl group content had a great impact on the Zeta potential and the free sulfhydryl group. The principal component analysis demonstrated a notable correlation between the total sulfhydryl group and both the Zeta potential and free sulfhydryl group of RRPI.
Quantity of delta‐9‐tetrahydrocannabinol consumption and cannabis use disorder among daily cannabis consumers
Authors: Borodovsky Jacob T. , Hasin Deborah S. , Wall Melanie , Struble Cara A. , Habib Mohammad I. , Livne Ofir , Liu Jun , Chen Lynn , Aharonovich Efrat , Budney Alan J.
Published: November 2024

Background and aims

Amid escalating cannabis legalization and daily consumption in the United States (US), determining the risk of cannabis use disorder (CUD) and relevant consequences among daily consumers has become a public health priority. Understanding these risks requires valid assessment of the daily quantity of delta‐9‐tetrahydrocannabinol (THC) consumed and its relation to consequences. This study characterized daily cannabis consumption using a new method for estimating milligrams of THC (mgTHC), and examined the relationship between daily mgTHC and CUD severity in a large national sample of daily consumers.

Design, setting and participants

US adult (aged 18+ years) daily cannabis consumers (n = 4134) completed a comprehensive online survey of cannabis consumption patterns (e.g. frequency, quantity, product types, potencies, administration methods) and Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM‐5) CUD criteria.

Measurements

The primary exposure was past‐week daily mgTHC consumption, calculated from survey responses to queries about product type, amount and potency consumed and including adjustments for puff size and loss of THC from specific methods of administration. The primary outcomes were (1) number of CUD criteria (range = 0–11) and (2) CUD severity categories: none, mild, moderate, severe.

Findings

Median daily consumption was ~130 mgTHC, with substantial variability (25% ≤ 50 mg and 25% ≥ 290 mg). On average, participants endorsed 2.5 CUD criteria, and 65% met criteria for CUD (39% mild, 18% moderate, 8% severe). Greater daily mgTHC predicted higher CUD criteria count [betalog(mgTHC) = 0.50, 95% confidence interval (CI) = 0.267–0.734] and higher odds of mild [log odds ratio (logOR) = 0.238, 95% CI = 0.184–0.292], moderate (logOR = 0.303, 95% CI = 0.232–0.374) or severe (logOR = 0.335, 95% CI = 0.236–0.435) CUD.

Conclusions

Among daily consumers of cannabis, there appears to be a positive relationship between the daily quantity of cannabis consumed (measured in milligrams of delta‐9‐tetrahydrocannabinol) and both the risk and severity of cannabis use disorder.
From side‐work to main task: Housing, status, and Tibetan labour migration in Qinghai, China
Authors: Zhaxi Duojie
Published: November 2024

Across China, as in other parts of the world, urbanisation has accelerated at an unprecedented scale over the past 15 years. In farming areas of Qinghai in western China, large‐scale rural–urban movement of Tibetan villagers began around 2010 – a time when state‐led housing subsidy projects were launched. Drawing on ethnographic field research and focusing on the older cohort of rural Tibetan migrants to Xining, the largest city on the Tibetan Plateau, this article explores the complexities and linkages between state‐led housing subsidy projects, status, and Tibetan labour migration. It examines how housing and family status intersect to shape patterns of Tibetan labour migration and gendered divisions of labour. This study highlights an important but less explored factor in migration studies: in my research sites, the recent large‐scale Tibetan labour migration to cities has been driven by the desire to build new houses to secure family status as a result of the motives and social pressure created by state‐led housing subsidy projects.
Effect of Antithyroid Drugs Treatment Duration on The Remission Rates of Graves' Disease in Children and Adolescents: A Single‐Arm Meta‐Analysis and Systematic Review
Authors: Li Yang , Wang Xin‐Meng , Shi Wen‐Yuan , Chen Jia‐Jia , Song Yan‐Ning , Gong Chun‐Xiu
Published: November 2024

Background

Antithyroid drugs (ATDs) are the preferred treatment option for Graves' disease (GD), yet there is a lack of systematic evaluations studying the relationship between treatment duration and therapeutic outcomes. This study aims to assess the remission rate (RR) in children with GD under ATDs therapy and to conduct an analysis of associated factors.

Method

Systematically searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure and Wanfang database, with a search time limit from the establishment of the database to 23 November 2023. The primary outcome was the RR. The pooled RR was calculated and subgroup comparisons were performed. Meta‐analysis was conducted using R Studio 2023.09.0 + 463 software.

Results

The study incorporated a total of 19 research projects, which collectively involved 3359 paediatric patients diagnosed with GD (comprising 2600 girls and 759 boys). The overall RR for paediatric GD treated with ATDs was 25.4% (95% Confidence Interval [CI]: 20.7%, 30.1%). The pooled RR following treatment durations of < 2 years, 2−5 years, and > 5 years were respectively 15.5%, 24.1% and 33.0%. Meta‐regression results indicated that the duration of treatment and follow‐up duration were significant sources of high heterogeneity among the studies. Specifically, for every additional year of ATDs treatment, there was an increase in the RR by 3.8% (Coefficient = 3.8%, 95% CI: 0.6%, 7.0%, p < 0.01).

Conclusion

The overall RR for the treatment of paediatric GD with ATDs is 25.4%, and prolonging the treatment course can indeed lead to an increased RR.
Lysine Acetyltransferase TIP60 Restricts Nerve Injury by Activating IKKβ/SNAP23 Axis‐Mediated Autophagosome‐Lysosome Fusion in Alzheimer's Disease
Authors: Wang Wei , Min Jun , Luo Qinghua , Gu Xunhu , Li Min , Liu Xu
Published: November 2024

Objective

The hyperphosphorylation of Tau protein is considered an important cause of neuronal degeneration in Alzheimer's disease (AD). The disruption of neuronal histone acetylation homeostasis mediated by Tip60 HAT is a common early event in neurodegenerative diseases, but the deeper regulatory mechanism on β‐amyloid peptide (Aβ)‐induced neurotoxicity and autophagic function in AD is still unclear.

Methods

AD models were established both in APP/PS1 mice and Aβ1–42‐treated SH‐SY5Y cells. The Morris water maze test (MWM) was performed to examine mouse cognitive function. Neurological damage in the hippocampus was observed by hematoxylin–eosin (H&E), Nissl's, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and NeuN staining. Autophagosome‐lysosome fusion was detected by immunohistochemistry, immunofluorescence, and Lyso‐Tracker Red staining. Cell viability and apoptosis were evaluated by CCK‐8 assay and flow cytometry. The molecular interactions were verified by co‐immunoprecipitation (Co‐IP), dual luciferase assays, and ChIP detections. The RNA and autophagy‐lysosome‐related proteins were assessed by Western blot and RT‐qPCR.

Results

TIP60 overexpression improved cognitive deficits and neurological damage and restored the impairment of autophagy‐lysosomes fusion in vivo. Similarly, the upregulation of TIP60 in Aβ1–42‐treated SH‐SY5Y cells suppressed neuronal apoptosis and tau phosphorylation through the activating autophagy‐lysosome pathway. Mechanistically, TIP60 activated IKKβ transcription by promoting SOX4 acetylation, thus leading to the translocation of SNAP23 to STX17‐contained autophagosomes. Moreover, the protective roles of TIP60 in neuron damage were abolished by the inhibition of SOX4/IKKβ signaling.

Conclusion

Collectively, our results highlighted the potential of the TIP60 target for AD and provided new insights into the mechanisms underlying neuroprotection in this disorder.
The Neuroprotection of 1,2,4‐Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke
Authors: Liu Xuan , Luo Jingning , Chen Jianwen , Huang Ping , He Gongyun , Ye Xueshi , Su Ruiqi , Lao Yaoqiang , Wang Yang , He Xiangjun , Zhang Jingxia
Published: November 2024

Background

The oxidative stress and neuroinflammation are important factors in acute ischemic stroke (AIS). Our former study showed the 1,2,4‐ triazole derivative (SYS18) had obviously neuroprotection by anti‐ oxidative stress on rat middle cerebral artery occlusion (MCAO) model.

Aim

In this study, we continue to investigate its neuroprotection by anti‐inflammatory effects and protecting BBB integrity in AIS.

Methods and Results

First, its effect on acute inflammation was evaluated by the mice model of increased peritoneal capillary permeability. Then, the MCAO cerebral edema models were built to evaluate its neuroprotection by reducing the neurological score, cerebral edema, improving the biochemical indicators, and pathological damage of brain tissue. At the same time, its protection on blood–brain barrier (BBB) integrity was proved by decreasing the BBB permeability and inhibiting glycocalyx degradation and regulating the BBB tight junction proteins expression of matrix metalloproteinase‐ 9 (MMP‐ 9) and claudin‐ 5 in brain tissue. Meanwhile, pharmacokinetic experiments showed that the compound had good BBB penetration. It has some advantages in the intensity of efficacy compared with the marketed drug edaravone.

Conclusion

Based on these findings, SYS18 has a strong potential to become a neuroprotectant in the future.
Nurse practitioner oversight ratios and labor market outcomes
Authors: Smith Andrew J. D. , Markowitz Sara
Published: November 2024

Nurse practitioners are important to the US healthcare system; however, many states impose physician oversight ratios, which limit the number of NPs a physician may supervise. In this study, we evaluate the effect of eliminating physician oversight ratios on the supply of NPs by conducting case studies of three states—New York, Nevada, and Pennsylvania—using synthetic control and related approaches. Surprisingly, we find that eliminating oversight ratios had little effect on the labor supply of NPs. For New York, we also analyze the effects of eliminating oversight ratios on wages and hours worked and again find null results.
Adapting to Individual Differences: An Experimental Study of Language Evolution in Heterogeneous Populations
Authors: Josserand Mathilde , Pellegrino François , Grosseck Oxana , Dediu Dan , Raviv Limor
Published: November 2024

Variations in language abilities, use, and production style are ubiquitous within any given population. While research on language evolution has traditionally overlooked the potential importance of such individual differences, these can have an important impact on the trajectory of language evolution and ongoing change. To address this gap, we use a group communication game for studying this mechanism in the lab, in which micro‐societies of interacting participants develop and use artificial languages to successfully communicate with each other. Importantly, one participant in the group is assigned a keyboard with a limited inventory of letters (simulating a speech impairment that individuals may encounter in real life), forcing them to communicate differently than the rest. We test how languages evolve in such heterogeneous groups and whether they adapt to accommodate the unique characteristics of individuals with language idiosyncrasies. Our results suggest that language evolves differently in groups where some individuals have distinct language abilities, eliciting more innovative elements at the cost of reduced communicative success and convergence. Furthermore, we observed strong partner‐specific accommodation to the minority individual, which carried over to the group level. Importantly, the degree of group‐wide adaptation was not uniform and depended on participants’ attachment to established language forms. Our findings provide compelling evidence that individual differences can permeate and accumulate within a linguistic community, ultimately driving changes in languages over time. They also underscore the importance of integrating individual differences into future research on language evolution.
Fiscal consolidation plans with underground economy
Authors: Ferrara Maria , Fiorelli Cristiana , Marzano Elisabetta , Varlese Monica
Published: November 2024

Fiscal consolidation literature often neglects that there are economies characterized by sizable underground sectors, with their mechanisms of response to fiscal policy shocks. Therefore, reliable analyses of fiscal consolidation plans call for the decomposition of Gross Domestic Product in its regular and hidden components. We investigate fiscal consolidation effects in the context of tax evasion for the Italian economy. Results show that a temporary cut in public spending associated with a permanent drop in tax rate yet entails tax evasion reduction. The main underlying mechanism is the strong responsiveness of the underground sector, implying a reallocation of resources toward the regular sector.
Loss in Overall and Quality‐Adjusted Life Expectancy for Patients With Chronic‐Phase Chronic Myeloid Leukemia
Authors: Chen Enoch Yi‐Tung , Dahlén Torsten , Stenke Leif , Björkholm Magnus , Hao Shuang , Dickman Paul W. , Clements Mark S.
Published: November 2024

The introduction of tyrosine kinase inhibitors has considerably improved the life expectancy (LE) for patients with chronic myeloid leukemia (CML). Evaluating health‐related quality of life within the treatment pathway remains crucial. Using the Swedish CML register, we included 991 adult patients with chronic‐phase (CP) CML diagnosed 2007 to 2017, with follow‐up until 2018. We developed a multistate model to estimate the loss in LE (LLE) and loss in quality‐adjusted life expectancy (LQALE) for the patient population compared to the general population, along with the respective proportions of losses relative to the general population. All patients with CP‐CML had a relatively low reduced LE but with larger LQALE. The maximum LLE within age/sex subgroups was 5.7 years (general population LE: 43.2 years vs. CP‐CML LE: 37.5 years) for females diagnosed at age 45 years, with LQALE of 12.0 quality‐adjusted life years (QALYs) (general population QALE: 38.2 QALYs vs. CP‐CML QALE: 26.3 QALYs). Across all ages, the proportions of LLE ranged from 9% to 15%, and the proportions of LQALE were 29% to 33%. Despite a low LLE, our findings reveal a greater LQALE for patients with CP‐CML. Further improvements in management of CP‐CML are thus warranted to successfully address the prevailing medical needs.
Inferior Overall Survival After Haploidentical Donor Lymphocyte Infusions in Relapsed Myeloid Neoplasms
Authors: Benoit Tobias Matthieu , Bachofner Adrian , Wolfensberger Nathan , Zaugg‐Berger Yvonne , Manz Markus Gabriel , Schneidawind Dominik
Published: November 2024

Objectives

Allogeneic hematopoietic stem cell transplantation (HSCT) effectively treats high‐risk myeloid neoplasms, but relapses post‐HSCT, particularly in acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS), pose significant challenges. Donor lymphocyte infusion (DLI) has been utilized, but its effectiveness, especially in haploidentical settings, remains insufficiently clarified, and graft‐versus‐host disease (GvHD) poses a substantial risk.

Methods

In this retrospective cohort study, 57 patients with AML or MDS who received DLI after allogeneic HSCT at our center from 2002 to 2023 were analyzed. Herein, only preemptively or therapeutically applied DLI were included, and endpoints included overall survival (OS), progression‐free survival (PFS), and GvHD incidence post‐DLI.

Results

Median OS after DLI was 517 days, with a 1‐year OS of 62.5%. Factors associated with longer OS included patient age, HLA‐identical donor, post‐HSCT treatment naivety, and preemptive DLI indication. Haploidentical DLI was associated with inferior OS compared to HLA‐identical DLI; however, PFS and GvHD incidence post‐DLI did not differ significantly.

Conclusions

Our study findings indicate that OS rate is inferior in patients with relapsed AML or MDS treated with haploidentical DLI in comparison to those who received HLA‐identical DLI. Given the limitations of haploidentical DLI, alternative strategies, such as higher cell doses or combination treatment approaches, warrant further investigation.
Imaging blood–brain barrier dysfunction in drug‐resistant epilepsy: A multi‐center feasibility study
Authors: Cafri Nir , Mirloo Sheida , Zarhin Daniel , Kamintsky Lyna , Serlin Yonatan , Alhadeed Laith , Goldberg Ilan , Maclean Mark A. , Whatley Ben , Urman Ilia , Doherty Colin P. , Greene Chris , Behan Claire , Brennan Declan , Campbell Matthew , Bowen Chris , Ben‐Arie Gal , Shelef Ilan , Wandschneider Britta , Koepp Matthias , Friedman Alon , Benninger Felix
Published: November 2024

Objective

Blood–brain barrier dysfunction (BBBD) has been linked to various neurological disorders, including epilepsy. This study aims to utilize dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) to identify and compare brain regions with BBBD in patients with epilepsy (PWE) and healthy individuals.

Methods

We scanned 50 drug‐resistant epilepsy (DRE) patients and 58 control participants from four global specialized epilepsy centers using DCE‐MRI. The presence and extent of BBBD were analyzed and compared between PWE and healthy controls.

Results

Both greater brain volume and higher number of brain regions with BBBD were significantly present in PWE compared to healthy controls (p < 10−7). No differences in total brain volume with BBBD were observed in patients diagnosed with either focal seizures or generalized epilepsy, despite variations in the affected regions. Overall brain volume with BBBD did not differ in PWE with MRI‐visible lesions compared with non‐lesional cases. BBBD was observed in brain regions suspected to be related to the onset of seizures in 82% of patients (n = 39) and was typically identified in, adjacent to, and/or in the same hemisphere as the suspected epileptogenic lesion (n = 10).

Significance

These findings are consistent with pre‐clinical studies that highlight the role of BBBD in the development of DRE and identify microvascular stabilization as a potential therapeutic strategy.
Long‐term neuroplasticity in language networks after anterior temporal lobe resection
Authors: Sablik Maria , Fleury Marine N. , Binding Lawrence P. , Carey David P. , d'Avossa Giovanni , Baxendale Sallie , Winston Gavin P. , Duncan John S. , Sidhu Meneka K.
Published: November 2024

Objective

Anterior temporal lobe resection (ATLR) is an effective treatment for drug‐resistant temporal lobe epilepsy (TLE), although language deficits may occur after both left and right ATLR. Functional reorganization of the language network has been observed in the ipsilateral and contralateral hemispheres within 12 months after ATLR, but little is known of longer‐term plasticity effects. Our aim was to examine the plasticity of language functions up to a decade after ATLR, in relation to cognitive profiles.

Methods

We examined 24 TLE patients (12 left [LTLE]) and 10 controls across four time points: pre‐surgery, 4 months, 12 months, and ~9 years post‐ATLR. Participants underwent standard neuropsychological assessments (naming, phonemic, and categorical fluency tests) and a verbal fluency functional magnetic resonance imaging (fMRI) task. Using a flexible factorial design, we analyzed longitudinal fMRI activations from 12 months to ~9 years post‐ATLR, relative to controls, with separate analyses for people with hippocampal sclerosis (HS). Change in cognitive profiles was correlated with the long‐term change in fMRI activations to determine the “efficiency” of reorganized networks.

Results

LTLE patients had increased long‐term engagement of the left extra‐temporal and contralateral temporal regions, with better language performance linked to bilateral activation. Those with HS exhibited more widespread bilateral activations. RTLE patients showed plasticity in the left extra‐temporal regions, with better language outcomes associated with these areas. Both groups of patients achieved cognitive stability over 9 years, with more than 50% of LTLE patients improving. Older age, longer epilepsy duration, and lower pre‐operative cognitive reserve negatively affected long‐term language performance.

Significance

Neuroplasticity continues for up to ~9 years post‐epilepsy surgery in LTLE and RTLE, with effective language recovery linked to bilateral engagement of temporal and extra‐temporal regions. This adaptive reorganization is associated with improved cognitive outcomes, challenging the traditional view of localized surgery effects. These findings emphasize the need for early intervention, tailored pre‐operative counseling, and the potential for continued cognitive gains with extended post‐ATLR rehabilitation.
Multi‐Objective Federated Averaging Algorithm
Authors: Geng Daoqu , Wang Shouzheng , Zhang Yihang
Published: November 2024

The recent global trend is the convergence of information and communications technology (ICT). By applying ICT in various fields such as the humanities, new types of products and services are created, and new values that help people's lives can be created. AI can be selected as a representative technology in such convergence ICT. However, applying AI technology to actual production requires ensuring data security. Federated learning (FL) can achieve secure sharing of data, where all parties participate in model training locally and upload it to the server for aggregation. The data never leaves the parties involved, thus solving the problems of data privacy and data silos. However, FL faces issues such as high communication cost, imbalanced performance distribution among participants, and low privacy protection. To achieve a balance between model accuracy, communication cost, fairness, and privacy, this paper proposes a multi‐objective optimization‐based FL algorithm (M‐FedAvg). The multi‐objective optimization problem of maximising the accuracy of the global model, minimising the communication cost, minimising the variance of the accuracy, and minimising the privacy budget is solved by NSGA‐III. The experimental results show that the algorithm proposed can effectively reduce the communication cost of FL and achieve privacy protection for participants without affecting the accuracy of the global model.
The Milan Approach today
Authors: Telfener Umberta , de Bustis Enzo , Cazzaniga Enrico , Ferrari Federico , Floris Roberta , Ganda Gianluca , Giordano Cinzia , Giuliani Massimo , La Barbera Chiara , Marchiori Roberta , Mosconi Andrea , Mreule Simona , Pasini Beppe , Pezzolo Monica , Rosas Ricardo , Sacchelli Davide , Sannasardo Piero , Sbattella Fabio , Tettamanzi Marilena , Troielli Walter , Trotta Barbara , Barazzetti Arianna
Published: November 2024

When asked what differentiates the Milan Approach now from the period when Luigi Boscolo and Gianfranco Cecchin were alive, the teachers at Via Leopardi remain humble. This article aims to explore the current identity of the Milan Approach. What is now the specificity of the Milan model? Do we have particularities that differentiate us from other clinical or therapeutic models? We still work according to the notion of the observing system, and we apply the three directives of the 1980s: hypothesizing, circularity, and curiosity. Is there a specific direction in which our approach is heading? Rather than attempting to take a picture of a status quo, this article seeks to represent the questions and doubts that organize a constant process in progress—as clinical work usually is. In this article, we wish to underline some aspects that are important to us and that we hold dear. We assert that the premises we have in common allow us to be flexible enough to keep in tune with current events and to address social issues that are of political relevance, in order to adapt to cultural changes.
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

Background

Small 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.

Objectives

To 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.

Methods

SCLC 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.

Results

Capivasertib 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.

Conclusion

Our 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

Aim

Epigenetic 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.

Methods

A 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.

Results

Monocytes 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).

Conclusions

DNA 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

In 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

This 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

Castleman 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

Undergraduate 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

This 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

Turkey 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

Aim

To explore healthcare workers' experiences of end of life care for people with an intellectual disability.

Design

A descriptive qualitative study.

Method

Semi‐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.

Results

Three major themes emerged: not joining up the dots, living the life desired in one's last days and dealing with death and beyond.

Conclusion

Gaps 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 Care

There 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.

Impact

This 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 Contribution

There 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

The 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

Background and Aim

Hepatitis 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.

Methods

Seven 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.

Results

ETV‐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.

Conclusions

In 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

Background

Coeliac 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.

Methods

Based 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.

Results

Based 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.

Conclusions

These guidelines cover nutritional and dietary assessment of patients with CeD, physical assessments, intake of oats, environmental considerations and the disease burden.