bluuebunny/crossref_metadata_2025_split huggingface dataset:
Esophageal chemoradiotherapy with concurrent nivolumab: Pilot results in the palliative treatment of oligometastatic disease
Authors: Day Fiona , Sridharan Swetha , Johnson Catherine , Quah Gaik T , Mallesara Girish , Kumar Mahesh , Poulter Amber‐Louise , Morrison Anthony , van der Westhuizen Andre , Fraser Allison , Oldmeadow Christopher , Martin Jarad 
Published: March 2024

AbstractAimsMany patients diagnosed with esophageal cancer have dysphagia from their primary tumor and de novo metastatic disease. The purpose of this study was to test the safety and efficacy of nivolumab given concurrently with hypofractionated chemoradiotherapy to patients with oligometastatic and obstructing esophageal tumors.MethodsPatients were enrolled in a planned single‐arm, phase 2 clinical trial. Eligible participants had previously untreated oligometastatic (≤5 metastases on fludeoxyglucose‐18 positron emission tomography scan outside the primary tumor radiotherapy field) esophageal or gastroesophageal carcinoma, dysphagia, and Eastern Cooperative Oncology Group performance status 0–1. Treatment was with 2 weeks of concurrent hypofractionated radiotherapy (30 Gy/10#) to the primary tumor, weekly carboplatin AUC2, weekly paclitaxel 50 mg/m2, and q2weekly nivolumab 240 mg, followed by nivolumab 480 mg continuing q4weekly until disease progression or 24 months total. A single metastasis was treated with stereotactic radiotherapy (SBRT) (24 Gy/3#) in week 7.ResultsFive patients were recruited before trial closure to new participants for logistical reasons. Existing participants continued treatment per protocol as a pilot study at one center. All five patients completed chemoradioimmunotherapy and SBRT. All patients derived an improvement in their dysphagia. Two patients completed 24 months of nivolumab without disease progression. Grade 3 adverse events (AEs) occurred in 3 patients, however, there were no grade 4 AEs, AEs due to SBRT, or AEs of special interest as defined by the protocol.ConclusionPilot results from five patients at one center found that treatment was well tolerated and effective for dysphagia relief. The efficacy of hypofractionated chemoradiotherapy with concurrent checkpoint inhibition should be tested in a multicentre study.
Application of three‐way mixed multivariate analysis of variance method to detect changes in chromatic coordinates (L*, a*, b*) in building granites
Authors: García‐Talegón J. , Iñigo A. C. , Paredes J. , Sepúlveda Correa R. A. , Azofra E. 
Published: March 2024

AbstractIn the present work we determined the chromatic coordinates (L*, a*, b*) for three building stones used in the heritage city of Ávila, Spain (World Granite Heritage City, 1988). The stones came from quarries and were subjected to 90 cycles of three types of accelerated ageing processes: (a) freezing/thawing together with cooling/heating (T1); (b) salt crystallisation (T2); and (c) freezing/thawing together with cooling/heating + salt crystallisation (T3). A three‐way mixed MANOVA (multivariate analysis of variance) was applied to the data obtained. Significant variations in the three chromatic coordinates (L*, a*, b*) were observed between the three types of accelerated artificial ageing processes compared to the data obtained from the quarry samples, with a tendency towards darkness (↓L*), redness (↑a*) and much less intensity towards yellowing (↑b*).
Crushing tablets or sprinkling capsules: Implications for clinical strategy and study performance based on BE studies of rivaroxaban and deferasirox
Authors: Sus Jan , Bosak Jan , Hauser Tomas 
Published: March 2024

AbstractAdministration of oral medicinal products as crushed tablets or open capsules is an important delivery option for patients suffering from dysphagia. To obtain full interchangeability of generics with the original products, demonstration of bioequivalence (BE) between both products administered as crushed tablets/open capsules was required for poorly soluble product by European Medicines Agency (EMA) at the time of development of our rivaroxaban and deferasirox generic products. We present the results of two BE studies with modified administration of these products, which compared relative bioavailability between generic and reference products. In the rivaroxaban study, the test product was administered as a capsule sprinkled on and mixed with applesauce, whereas the reference tablet was crushed and administered with applesauce under fed conditions. In the deferasirox study, both treatments were administered as crushed tablets under fasting conditions. Both studies applied a two‐way crossover design and were conducted after a single‐dose in healthy volunteers. The 90% confidence interval of the geometric mean ratio area under the analyte concentration versus time curve, from time zero to the time of the last measurable analyte concentration and maximum measured analyte concentration over the sampling period of the test to reference ratio were 103.36–110.37% and 97.98–108.45% for rivaroxaban, respectively, and 96.69–107.29% and 94.19–109.45% for deferasirox, respectively. Thus, the BE criteria (80.00–125.00%) were met in both studies which demonstrated that bioavailability was not affected when the test and reference products were administered in the form of crushed tablet/open capsule. These results support the argument of redundancy of crushed product studies for poorly soluble drugs, which is in line with the currently revised position of the EMA on this topic.
Trends in purchasing cross‐border, illicit and home‐brewed alcohol: A population study in Great Britain, 2020–2023
Authors: Jackson Sarah E. , Oldham Melissa , Angus Colin , Holmes John , Brown Jamie 
Published: March 2024

AbstractIntroductionThe last 3 years have seen substantial changes in Great Britain (GB) including the COVID‐19 pandemic, cost‐of‐living crisis and policy changes such as minimum unit pricing. We examined changes in purchasing cross‐border, illicit and home‐brewed alcohol among risky drinkers over this period.MethodsData were used from 22,086 adult (≥18 years) increasing/higher‐risk drinkers (AUDIT‐C ≥5) participating in a monthly cross‐sectional survey between October 2020 and August 2023. We estimated time trends in the proportion reporting obtaining alcohol from: (i) cross‐border (any/within‐GB/international); (ii) illicit; and (iii) home‐brewed sources in the past 6 months.ResultsBetween October 2020 and August 2023, the proportion reporting cross‐border alcohol purchases increased (from 8.5% to 12.5% overall; prevalence ratio [PR] = 1.47 [95% CI 1.17–1.86]). This was largely driven by an increase in cross‐border purchases abroad (PR = 1.52 [1.13–2.05]), with a smaller, uncertain increase in cross‐border purchases within GB (PR = 1.37 [0.96–1.95]). The prevalence of cross‐border alcohol purchasing was higher in Wales (13.8% [12.3–15.4%]) and Scotland (6.1% [5.4–6.8%]) than England (3.6% [3.3–3.9%]). There was little change in illicit alcohol purchasing in England or Wales (4.1% [3.7–4.4%]; 4.2% [3.2–5.1%]), but in Scotland it fell from 5.7% to 2.4% (PR = 0.42 [0.19–0.81]). Home‐brewed alcohol was rare (GB: 3.1% [2.9–3.4]) and stable.Discussion and ConclusionsThe proportion of increasing/higher‐risk drinkers in GB purchasing cross‐border alcohol increased between October 2020 and August 2023, due to an increase in people buying alcohol abroad. Cross‐border alcohol purchases within GB were more commonly reported in Wales and Scotland. The small proportion purchasing illicit alcohol did not change substantially in England or Wales, but fell by half in Scotland.
NUCB1 is required for proper insulin signaling to control longevity in Drosophila
Authors: Yoon Jong‐Won , Baek Si‐Eun , Yang Jae‐Yoon , Yeom Eunbyul 
Published: March 2024

AimWe examined the novel role of NUCB1(Nucleobindin‐1) associated with longevity in Drosophila melanogaster.MethodsWe measured the lifespan, metabolic phenotypes, and mRNA levels of Drosophila insulin‐like peptides (Dilps), the protein level of phosphorylated AKT, and the localization of FOXO and its target gene expressions in the NUCB1 knockdown condition.ResultsNUCB1 knockdown flies show an extended lifespan and metabolic phenotypes such as increased circulating glucose level and starvation resistance. The mRNA expression levels of Dilps and the protein level of phosphorylated AKT, a downstream component of insulin signaling, were decreased in NUCB1 knockdown flies compared with the control flies. Also, the nuclear localization of FOXO and its target gene expressions, such as d4E‐BP and InR, were elevated.ConclusionsThe results show that NUCB1 knockdown flies exhibits an extended lifespan. These findings suggest that NUCB1 modulates longevity through insulin signaling in Drosophila. Geriatr Gerontol Int 2024; 24: 486–492.
The evolution of home‐state positions towards diaspora formation: Israel and its two diasporas
Authors: Grossman Jonathan 
Published: March 2024

AbstractHow do home‐state elites react to emigrants who form diaspora communities abroad, and how do these attitudes change over time? The article explores these questions through an analysis of the discourse and policies of Israeli elites towards emigrants who created distinct diaspora communities and established ties with local Jewish diaspora communities between 1977 and 2023. The article highlights the important role that ethnic and national identities and the prospects of emigrants’ eventual return play in such attitudinal shifts. The home state may initially see diaspora formation as harmful for precipitating emigration and obstructing repatriation and ethnic immigration. However, when it becomes clear that the return of many emigrants is unlikely, home‐state elites may come to support and even promote the formation of new diaspora communities and their ties with older diaspora communities to offset emigrants’ assimilation into their host society and increase their attachment to the home state.
Catchment‐Wide Groundwater Budget for the Inkomati‐Usuthu Water Management Area in South Africa
Authors: Shakhane Teboho , Mojabake Moses 
Published: March 2024

AbstractIn South Africa, approximately 98% of the predicted total surface water resources are already being used up. Consequently, the National Water Resource Strategy considers groundwater to be important for the future planning and management of water resources. In this case, quantifying groundwater budgets is a prerequisite because they provide a means for evaluating the availability and sustainability of a water supply. This study estimated the regional groundwater budgets for the Inkomati‐Usuthu Water Management Area (Usuthu, Komati, Sabie‐Sand, and Crocodile) using the classical hydrological continuity equation. The equation was used to describe prevailing feedback loops between groundwater draft, recharge, baseflow, and storage change. The results were coarser scale estimates which, beforehand, were derived from the 2006 study. In the years to follow, groundwater reliance intensified and there was also the historic 2015/2016 drought. This inevitably led to an increased draft while the rest of the components of the groundwater budgets experienced decreases. Both Crocodile and Sabie‐Sand experienced groundwater storage depletion which led to reduced baseflow and groundwater availability, while groundwater recharge contrarily increased due to capture. Conversely, the other two catchments experienced relatively lower drafts with correspondingly higher groundwater availability and recharge while storage change was positive. The results highlighted the need for adaptive water management whose effectiveness relies on predictive studies. Consequently, future models should be developed to capture the spatial and temporal dynamism of the natural groundwater budget due to climate change, water demands, and population growth predictions.
A comparison of radiographically determined periapical healing and tooth survival outcomes of root canal (re)treatment performed in two care pathways within the United Kingdom Armed Forces
Authors: Smith Robert , Drummond Karl , Lovell Alistair , Ng Yuan‐Ling , Gulabivala Kishor , Bryce Graeme 
Published: March 2024

AbstractAimsTo compare radiographic periapical healing and tooth survival outcomes of root canal (re)treatment performed within two care pathways (Routine Dental Care and Referred Treatment Pathway), in the United Kingdom Armed Forces (UKAF), and determine the effects of endodontic complexity on outcomes.MethodologyThis retrospective cohort study included 1466 teeth in 1252 personnel who received root canal (re)treatment between 2015 and 2020. General Dental Practitioners treated 661 teeth (573 patients) (Routine cohort), whilst Dentists with a Special Interest treated 805 teeth (678 patients) (Referred cohort). The latter group were graduates of an MSc programme in Endodontics with 4–8 years of postgraduation experience. Case complexity was retrospectively determined for each tooth using the endodontic component of Restorative Index of Treatment Need (RIOTN) guidelines. Periapical healing was determined using loose radiographic criteria. The data were analysed using chi‐square tests, univariate logistic regression and Cox proportional hazards models.ResultsA significantly (p < 0.0001) larger proportion of cases of low complexity had undergone root canal treatment within the Routine versus Referred cohort. The odds of periapical healing was significantly higher within the Referred versus Routine cohort, regardless of analyses using pooled (OR = 1.17; 95% CI: 1.11, 1.22) or moderate complexity (OR = 4.71; 95% CI: 2.73, 8.11) data. Within the Routine cohort, anterior teeth had higher odds of periapical healing than posterior teeth (OR = 1.13; 95% CI: 1.04, 1.22). The 60‐month cumulative tooth survival was lower (p = 0.03) in the Routine (90.5%) than the Referred (96.0%) cohort. Within the Routine cohort, the hazard of tooth loss was higher amongst posterior teeth (HR = 4.03; 95% CI: 1.92, 8.45) but lower if posterior teeth had cast restorations (HR = 0.36; 95% CI: 0.19, 0.70). For the Referred cohort, posterior teeth restored with cast restoration (vs not) had significantly lower risk of tooth loss (HR = 0.21; 95% CI: 0.08, 0.55).ConclusionsFor UKAF patients, root canal (re)treatment provided within the Referred pathway was significantly more likely to achieve periapical healing and better tooth survival than those provided within the Routine pathway. Posterior teeth restored with an indirect restoration had a higher proportion of tooth survival. This study supported the utility of the endodontic component of RIOTN for assessing case complexity.
Effects of pronominal reference on the integration of syntactic and semantic information in second language processing
Authors: Kim Hyunwoo , Hwang Haerim 
Published: March 2024

AbstractThis study investigated the effect of pronominal reference on the integration of syntactic and semantic information in second language (L2) processing. We conducted a self‐paced reading task involving 60 adult Korean‐speaking learners of English and 44 native English speakers. The experiment manipulated the semantic congruity between a subject and its adjectival predicate, as well as the reference type (pronoun vs. full noun) within the intervening relative clause. The results showed that the native speaker group consistently displayed sensitivity to the incongruity between the subject and the predicate, regardless of the reference type. Similarly, the nonnative speakers exhibited sensitivity to the mismatch in the critical region. However, this effect did not persist in subsequent regions including the spill‐over and wrap‐up regions. Instead, in the wrap‐up region, the L2 learners’ processing patterns were affected by the reference type, with sensitivity exclusively observed in the pronoun condition. The L2 learners’ processing pattern remained consistent across varying levels of English proficiency. These findings provide insights into the role of pronominal reference in L2 sentence processing.
Integrating genomics into Canadian oncology nursing policy: Insights from a comparative policy analysis
Authors: Chiu Patrick , Limoges Jacqueline , Pike April , Calzone Kathleen , Tonkin Emma , Puddester Rebecca , Gretchev Andrea , Dewell Sarah , Newton Lorelei , Leslie Kathleen 
Published: March 2024

AbstractAimTo learn from two jurisdictions with mature genomics‐informed nursing policy infrastructure—the United States (US) and the United Kingdom (UK)—to inform policy development for genomics‐informed oncology nursing practice and education in Canada.DesignComparative document and policy analysis drawing on the 3i + E framework.MethodsWe drew on the principles of a rapid review and identified academic literature, grey literature and nursing policy documents through a systematic search of two databases, a website search of national genomics nursing and oncology nursing organizations in the US and UK, and recommendations from subject matter experts on an international advisory committee. A total of 94 documents informed our analysis.ResultsWe found several types of policy documents guiding genomics‐informed nursing practice and education in the US and UK. These included position statements, policy advocacy briefs, competencies, scope and standards of practice and education and curriculum frameworks. Examples of drivers that influenced policy development included nurses' values in aligning with evidence and meeting public expectations, strong nurse leaders, policy networks and shifting healthcare and policy landscapes.ConclusionOur analysis of nursing policy infrastructure in the US and UK provides a framework to guide policy recommendations to accelerate the integration of genomics into Canadian oncology nursing practice and education.Implications for the professionFindings can assist Canadian oncology nurses in developing nursing policy infrastructure that supports full participation in safe and equitable genomics‐informed oncology nursing practice and education within an interprofessional context.ImpactThis study informs Canadian policy development for genomics‐informed oncology nursing education and practice. The experiences of other countries demonstrate that change is incremental, and investment from strong advocates and collaborators can accelerate the integration of genomics into nursing. Though this research focuses on oncology nursing, it may also inform other nursing practice contexts influenced by genomics.
Neuroendocrine and cellular mechanisms in stress resilience: From hormonal influence in the CNS to mitochondrial dysfunction and oxidative stress
Authors: Bhattacharya Arghya , Chakraborty Manas , Chanda Ananya , Alqahtani Taha , Kumer Ajoy , Dhara Bikram , Chattopadhyay Moitreyee 
Published: March 2024

AbstractRecent advancements in neuroendocrinology challenge the long‐held belief that hormonal effects are confined to perivascular tissues and do not extend to the central nervous system (CNS). This paradigm shift, propelled by groundbreaking research, reveals that synthetic hormones, notably in anti‐inflammatory medications, significantly influence steroid psychosis, behavioural, and cognitive impairments, as well as neuropeptide functions. A seminal development in this field occurred in 1968 with McEven's proposal that rodent brains are responsive to glucocorticoids, fundamentally altering the understanding of how anxiety impacts CNS functionality and leading to the identification of glucocorticosteroids and mineralocorticoids as distinct corticotropic receptors. This paper focuses on the intricate roles of the neuroendocrine, immunological, and CNS in fostering stress resilience, underscored by recent animal model studies. These studies highlight active, compensatory, and passive strategies for resilience, supporting the concept that anxiety and depression are systemic disorders involving dysregulation across both peripheral and central systems. Resilience is conceptualized as a multifaceted process that enhances psychological adaptability to stress through adaptive mechanisms within the immunological system, brain, hypothalamo–pituitary–adrenal axis, and ANS Axis. Furthermore, the paper explores oxidative stress, particularly its origin from the production of reactive oxygen species (ROS) in mitochondria. The mitochondria's role extends beyond ATP production, encompassing lipid, heme, purine, and steroidogenesis synthesis. ROS‐induced damage to biomolecules can lead to significant mitochondrial dysfunction and cell apoptosis, emphasizing the critical nature of mitochondrial health in overall cellular function and stress resilience. This comprehensive synthesis of neuroendocrinological and cellular biological research offers new insights into the systemic complexity of stress‐related disorders and the imperative for multidisciplinary approaches in their study and treatment.
The global sanitary revolution in historical perspective
Authors: Gallardo‐Albarrán Daniel 
Published: March 2024

AbstractThis survey sheds light on the causes and consequences of the global sanitary revolution that resulted in the spread of waterworks and sewerage projects since the middle of the 19th century, by drawing on research from the fields of economic history, economics, and history. I begin with a discussion of the construction of these infrastructures during the period ca. 1850–1950 showing that their spread was relatively similar in major urban cities across the globe, while diffusion within and between countries, as well as within cities themselves, was markedly unequal. Second, I review research estimating the mortality impact of access to clean water and sanitation. Following the provision of these services, infant mortality declined between ca. 10 and 30 percent. Lastly, I examine the drivers of the sanitary revolution with a new framework that distinguishes between proximate factors (e.g., physical capital) and ultimate factors (e.g., institutions). I argue that the state of knowledge in the literature is insufficient to explain between‐ and within country differences in access to sanitary services and that more attention should be devoted to the interaction of political and economic factors within broader institutional, cultural and biogeographic contexts.
Statistical inference for generative adversarial networks and other minimax problems
Authors: Meitz Mika 
Published: March 2024

AbstractThis paper studies generative adversarial networks (GANs) from the perspective of statistical inference. A GAN is a popular machine learning method in which the parameters of two neural networks, a generator and a discriminator, are estimated to solve a particular minimax problem. This minimax problem typically has a multitude of solutions and the focus of this paper are the statistical properties of these solutions. We address two key statistical issues for the generator and discriminator network parameters, consistent estimation and confidence sets. We first show that the set of solutions to the sample GAN problem is a (Hausdorff) consistent estimator of the set of solutions to the corresponding population GAN problem. We then devise a computationally intensive procedure to form confidence sets and show that these sets contain the population GAN solutions with the desired coverage probability. Small numerical experiments and a Monte Carlo study illustrate our results and verify our theoretical findings. We also show that our results apply in general minimax problems that may be nonconvex, nonconcave, and have multiple solutions.