bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of FcRn with rozanolixizumab in adults with immune thrombocytopenia: Two randomised, double‐blind, placebo‐controlled phase 3 studies and their open‐label extension
Authors: Cooper Nichola , Bussel James B. , Kaźmierczak Maciej , Miyakawa Yoshitaka , Cluck Sarah , Lledó García Rocío , Haier Birgit , Lavrov Andreea , Singh Puneet , Snipes Rose , Kuter David J.
Published: November 2024

Primary immune thrombocytopenia (ITP) is an antiplatelet‐antibody‐mediated disorder with accelerated platelet clearance and decreased platelet production. Rozanolixizumab, a monoclonal IgG4 anti‐FcRn antibody, blocks IgG recycling and decreases IgG levels. We report efficacy and safety of rozanolixizumab in adults with persistent/chronic ITP in 24‐week phase 3 studies (TP0003; TP0006), and their 52‐week open‐label extension (OLE). Primary end‐point was durable clinically meaningful platelet response (DCMPR) of ≥50 × 109/L for 8/12 weeks during Weeks 13–25 in the double‐blind studies. Operational delays and evolving ITP treatment landscape led the sponsor to terminate these studies early; thus, only 21 and 12 (TP0003) and 20 and 10 (TP0006) patients were randomised to rozanolixizumab or placebo. Forty‐three patients enrolled in the OLE: 42 started on every 2‐week dosing; 21 later switched to weekly dosing. More rozanolixizumab‐treated than placebo‐treated patients achieved DCMPR: 4/21 versus 0 (TP0003) and 1/20 versus 0 (TP0006). Platelet increases to ≥50 × 109/L were observed on Day 8 in 52.4% (TP0003; 2/12 placebo) and 45.0% (TP0006; 1/10 placebo) of rozanolixizumab‐treated patients. OLE platelet increases were maintained while on weekly dosing. The most frequent treatment‐emergent adverse events overall were headache, pyrexia and nausea, as seen previously. Weekly dosing appears more efficacious than every 2‐week dosing.
Alone together? A time use approach for examining socializing when travel is limited
Authors: DeJohn Amber , Liu Bochu , Ma Xinlin , Widener Michael J. , Liu Zhilin
Published: November 2024

Migrant populations access different social networks due to their cultural contexts and the locations of their social relationships. The COVID‐19 pandemic generated concern about social isolation among older adults. During Ontario's extended lockdown, we investigated the social behaviours of a generally sedentary older Chinese migrant community (n = 77) in the Greater Toronto Area. Using single‐day activity diaries, we grouped respondents using a k‐means clustering approach, which resulted in four categories of socializing characteristics. We then used ANOVA tests and multinomial logistic regression to understand the geographic contexts for these socializing behaviours. Findings reveal that this older migrant community was mostly socializing online, but a small group reported socializing in person. Living in a house, having better physical health, and having children living abroad was associated with a higher likelihood of socializing in person rather than online. Ultimately, it is important to understand the context within which older migrants socialize in order to support social connection and related health outcomes as they age.
Parents spontaneously scaffold the formation of conversational pacts with their children
Authors: Leung Ashley , Yurovsky Daniel , Hawkins Robert D.
Published: November 2024

Adults readily coordinate on temporary pacts about how to refer to things in conversation. Young children are also capable of forming pacts with peers given appropriate experimenter intervention. Here, we investigate whether parents may spontaneously provide a similar kind of scaffolding with U.S. children in a director–matcher task (N = 201, 49% female; ages 4, 6, 8). In Experiment 1, we show that parents initiate more clarification exchanges with younger children who, in turn, are more likely to adopt labels introduced by the parent. We then examine whether the benefit of such scaffolding acts primarily through childrens' difficulties with comprehension (Experiment 2) or production (Experiment 3). Our findings suggest that parents primarily scaffold pacts by easing children's production difficulties, modeling cooperative communication.
BRCC3‐Associated Syndromic Moyamoya Angiopathy Diagnosed Through Clinical RNA Sequencing
Authors: Venema Myrrhe , Albuainain Fatimah , Schot Rachel , Roozenbeek Bob , Sleutels Frank , van Ham Tjakko , Barakat Tahsin Stefan
Published: November 2024

Moyamoya angiopathy is a cerebral vasculopathy causing progressive stenosis of the internal carotid arteries and the compensatory development of collateral blood vessels, leading to brain ischemia and an increased risk of cerebral haemorrhage. Although multiple non‐genetic causes have been associated with moyamoya syndrome, it can also be associated with rare genetic syndromes. Moyamoya Disease 4, characterised by a short stature, hypergonadotropic hypogonadism and facial dysmorphism (MYMY4, OMIM #300845), also referred to as BRCC3‐associated moyamoya syndrome, has so far been described in 11 individuals. Here, we describe a 23‐year‐old male presenting with moyamoya syndrome, global developmental delay and intellectual disability, epilepsy, short stature and dysmorphic features, who after > 17 years of uninformative diagnostics was diagnosed with BRCC3‐associated moyamoya syndrome after clinical RNA‐seq. Transcriptome analysis showed reduced expression of the likely disease‐causing gene BRCC3 in patient‐derived fibroblasts, which was subsequently found to be caused by a ~ 26 kb Xq28 deletion. We furthermore review all reported cases of BRCC3‐associated moyamoya syndrome, further delineating this clinical entity.
Lay Theories of Moral Progress
Authors: Lewry Casey , Asifriyaz Sana , Lombrozo Tania
Published: November 2024

Many consider the world to be morally better today than it was in the past and expect moral improvement to continue. How do people explain what drives this change? In this paper, we identify two ways people might think about how moral progress occurs: that it is driven by human action (i.e., if people did not actively work to make the world better, moral progress would not occur) or that it is driven by an unspecified mechanism (i.e., that our world is destined to morally improve, but without specifying a role for human action). In Study 1 (N = 147), we find that those who more strongly believe that the mechanism of moral progress is human action are more likely to believe their own intervention is warranted to correct a moral setback. In Study 2 (N = 145), we find that this translates to intended action: those who more strongly believe moral progress is driven by human action report that they would donate more money to correct a moral setback. In Study 3 (N = 297), participants generate their own explanations for why moral progress occurs. We find that participants’ donation intentions are predicted by whether their explanations state that human action drives moral progress. Together, these studies suggest that beliefs about the mechanisms of moral progress have important implications for engaging in social action.
Current and future climate suitability for the hazel dormouse in the UK and the impact on reintroduced populations
Authors: Cartledge Emma L. , Bellis Joe , White Ian , Hurst Jane L. , Stockley Paula , Dalrymple Sarah
Published: November 2024

Reintroductions are increasingly being used as a conservation tool to restore species to areas where they once existed. Unfortunately, many reintroduction projects fail to establish viable populations. Climate suitability at release sites is thought to be important in determining reintroduction outcomes, and future climate change is an essential consideration for effective reintroduction planning. Climate change threatens species in a variety of ways, such as by impacting life history traits or causing spatial and temporal distribution mismatches of interdependent species. Hibernating species, such as the hazel dormouse (Muscardinus avellanarius), may be particularly susceptible to changes in climate. For example, milder winters may increase the number of interbout arousals during hibernation, which are energetically costly. Timing of food availability may also be impacted by changing climates, potentially causing mismatches between activity and feeding opportunities. Here, we use species distribution models (SDMs) to map climate suitability for dormice in the UK. We also investigate the impact of climate suitability on a long‐running dormouse reintroduction programme, providing the first such investigation for a reintroduced mammal. We find that higher levels of current climate suitability increase the probability of reintroduction success. We find no effect of climate suitability on adult dormouse counts at reintroduction sites, but dormouse counts decline with time since reintroduction. Future projections predict that climate change may lead to more widespread climate suitability for dormice in the UK, reflecting predicted changes in seasonality, winter temperature and precipitation. Our work demonstrates the importance of understanding changing climate suitability for reintroduction planning, with potential widespread applications of SDMs for conservation projects of low‐dispersing mammals.
Calcineurin‐Inhibitor Discontinuation Could Reduce the Risk of De Novo Malignancies After Liver Transplantation for Alcohol‐Related Liver Disease
Authors: Erard Domitille , Steiner Anouk , Boillot Olivier , Thimonier Elsa , Vallin Mélanie , Veyre Florian , Guillaud Olivier , Radenne Sylvie , Dumortier Jérôme
Published: November 2024

Background

De novo malignancies are one of the leading causes of death after liver transplantation (LT), particularly in patients transplanted for alcohol‐related liver disease (ALD). This retrospective study aimed to assess risk factors for malignancies and to evaluate the impact of calcineurin inhibitor (CNI) discontinuation.

Methods

From 1990 to 2015, all patients transplanted for ALD were included.

Results

A total of 493 patients were included, 77.9% were male and the median age at LT was 54 years. After LT, 278 de novo malignancies were diagnosed in 214 patients (43.4%). The cumulative incidence of de novo malignancies was 16.3% at 5 years, 34.4% at 10 years, and 49.8% at 15 years. In multivariate analysis, the independent risk factors were male gender (HR = 1.6), and active or weaned smoking (HR = 2.0). Discontinuation of CNI was a protective factor (HR = 0.6). Survival after diagnosis of de novo malignancy was 42.7% at 5 years and 27.5% at 10 years.

Conclusion

Our results confirm the major incidence of de novo malignancies after LT for ALD, as well as the important role of non‐modifiable risk factors such as smoking and gender. CNI discontinuation is a protective factor, and the only adaptable, and could be proposed in smoker male patients transplanted for ALD.
Imetelstat, a novel, first‐in‐class telomerase inhibitor: Mechanism of action, clinical, and translational science
Authors: Lennox Ashley L. , Huang Fei , Behrs Melissa Kelly , González‐Sales Mario , Bhise Neha , Wan Ying , Sun Libo , Berry Tymara , Feller Faye , Morcos Peter N.
Published: November 2024

Most cancers and neoplastic progenitor cells have elevated telomerase activity and preservation of telomeres that promote cellular immortality, making telomerase a rational target for the treatment of cancer. Imetelstat is a first‐in‐class, 13‐mer oligonucleotide that binds with high affinity to the template region of the RNA component of human telomerase and acts as a competitive inhibitor of human telomerase enzymatic activity. Pharmacokinetics, pharmacodynamics, exposure‐response analyses, efficacy, and safety of imetelstat have been evaluated in vitro, in vivo, and clinically in solid tumor and hematologic malignancies, including lower‐risk myelodysplastic syndromes (LR‐MDS) and myeloproliferative neoplasms. Imetelstat was approved in the United States in June 2024 for the treatment of adult patients with LR‐MDS with transfusion‐dependent anemia requiring four or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis‐stimulating agents, with a recommended dosing regimen of 7.1 mg/kg administered via 2‐h intravenous infusion every 4 weeks. In the pivotal trial, significantly more patients treated with imetelstat versus placebo achieved ≥8‐week and ≥24‐week red blood cell‐transfusion independence, and imetelstat was associated with a manageable safety profile characterized primarily by short‐lived and manageable neutropenia and thrombocytopenia. This mini‐review summarizes the mechanism of action, pharmacokinetic and pharmacodynamic characteristics, clinical development, and clinical efficacy and safety data of imetelstat.
Efficacy and safety of tofacitinib in rheumatoid arthritis: Nine years of real‐world data
Authors: Ekin Ali , Misirci Salim , İldemir Selin , Coskun Belkıs Nihan , Yagiz Burcu , Dalkilic Ediz , Pehlivan Yavuz
Published: November 2024

Tofacitinib is a targeted JAK inhibitor used to treat rheumatoid arthritis. Despite some recent safety concerns, it is considered effective and safe with appropriate patient selection. Between May 2015 and May 2024, data were retrospectively analyzed from 112 patients with a diagnosis of RA in a tertiary care hospital who had received tofacitinib for at least 1 month, with or without prior biologic DMARDs. The mean disease duration was 12 years, and the median duration of tofacitinib use was 32.5 months. The p‐value for all disease activity parameters evaluated for effectiveness between the 1st‐ and 3rd‐month visits was <0.001, except CRP (p = 0.097). Adverse events occurred in 15 (13.4%) patients, with an incidence rate of 4.54 per 100 patient‐years. Observed were one myocardial infarction (0.3/100 patient‐years), two pulmonary embolisms (0.6/100 patient‐years), three herpes zoster (HZ) (0.9/100 patient‐years), and one basal cell carcinoma (BCC) (0.3/100 patient‐years). Median drug‐free survival was 68 (95% CI: 54.8–81.2) months. The drug was discontinued in 28 (25%) patients due to ineffectiveness and in 13 (11.6%) due to side effects. A significant difference in drug survival rates was observed between patients who had not previously used bDMARDs and those who had received at least one bDMARD before tofacitinib (p < 0.001). Drug survival was 46.35 months in the prior bDMARD group and 71.09 months in the bDMARD‐naive group. This study found significant reductions in disease activity indices at 3 and 6 months after starting tofacitinib, with sustained effectiveness. Although adverse event rates were somewhat higher than reported in the literature, tofacitinib can be used effectively and safely in appropriate patient populations for RA treatment.
The right to counsel: criminal prosecution in 19th century London
Authors: McCannon Bryan C. , Porreca Zachary
Published: November 2024

We exploit a dataset of criminal trials in 19th century London to evaluate the impact of an accused's right to counsel on convictions. While lower‐level crimes had an established history of professional representation prior to 1836, individuals accused of committing a felony did not, despite the prosecution being conducted by professional attorneys. The Prisoners' Counsel Act 1836 remedied this and first introduced the right to counsel in common law systems. Using a difference‐in‐differences estimation strategy, we identify the effect of the universal right to defence counsel. We find the surprising result that the professionalization of the courtroom led to an increase in the conviction rate. We argue that this effect was a consequence of the Act inducing a shift in the beliefs of jurors, who grew more likely to believe the evidence put before them once it could be challenged in an adversarial courtroom. We go further, and employ a topic modelling approach to the text of the transcripts to provide suggestive evidence on how the trials changed when the right to defence counsel was fully introduced, documenting a movement towards increased usage of precise and detailed language when discussing details of alleged offences.
Parenthood and occupational mobility
Authors: Liu Andrew Yizhou
Published: November 2024

I show that parenthood contributes to the downward‐sloping age‐occupational‐mobility profile. After the birth of the first child, men experience a 20% decline in occupational switching which is uniform across upward and downward mobility. For women, the decline is 14%, which is larger for upward than for downward occupational mobility. Therefore, parenthood can explain 22% and 12% of the declines in occupational mobility for working men and women between 25 and 45 years of age, respectively. Workers in disadvantaged groups experience larger decreases, highlighting the potential impacts of parenthood on their occupational choices.
Teaching Controversial Issues under Conditions of Political Polarization: A Case for Epistemic Refocusing
Authors: Torres Eric
Published: November 2024

Educating students for democratic life requires teachers to make difficult judgment calls about whether controversial issues are appropriate for directive teaching (i.e., teaching that attempts to persuade students to adopt a particular view about the thing being taught). To help educators make these decisions, theorists have proposed criteria for systematically differentiating between issues that do and do not qualify for directive teaching. Unfortunately, the epistemic environment of political polarization degrades educators' abilities to reliably assess whether a broad class of politically contested issues meet these criteria for directive teaching. In this paper Eric Torres argues that, while making judgments about whether individual cases warrant directive teaching remains essential and inevitable, educators can best address this problem by engaging in a practice of epistemic refocusing that makes the conditions of educators' own deliberations salient to students, thereby hedging against the effects of bad calls about which issues to teach directively while simultaneously illuminating the constraints of polarization on political cognition, an awareness that is essential to healthy democratic participation in the twenty‐first century.
Effect of masticatory muscle function on the craniofacial sutures of the anterior viscerocranium in growing rats
Authors: Gorucu‐Coskuner Hande , Al‐Yassary Mustafa , Billiaert Kelly , Kiliaridis Stavros , Antonarakis Gregory S.
Published: November 2024

The transverse dimensions of internasal and nasopremaxillary sutures in rats were assessed at different ages and following different dietary functional demands.Eighty‐four male Wistar rats were divided into two groups fed either a hard or a soft diet from 4 weeks of age, and sacrificed at 4 weeks (baseline: n = 12),16 weeks (n = 24), 26 weeks (n = 24), or 38 weeks (n = 24) of age. High‐resolution micro‐computed tomograms of the internasal and left nasopremaxillary sutures were obtained with 10 µm voxel size and 5 × 5 mm field of view. The endocranial and ectocranial suture widths, the mean suture width, and the suture height were measured. Linear regression analysis was used to estimate the effects of age and type of diet on suture dimensions. Internasal and nasopremaxillary suture dimensions were influenced by age, with a generally lower width and a larger height in the older animal. Regarding diet consistency, internasal suture widths were on average larger in the hard‐diet group (e.g., mean suture width 43 µm in the hard‐ versus 30 µm in the soft‐diet group at 26 weeks). In conclusion, the internasal and nasopremaxillary sutures tend to become narrower with age, while being influenced by masticatory functional demands.
Interleukin‐33 Deficiency Protects the Skin From Ulcer Formation in an Ischemia–Reperfusion‐Induced Decubitus Mouse Model
Authors: Jin Meijuan , Komine Mayumi , Tsuda Hidetoshi , Sashikawa‐Kimura Miho , Nakae Susumu , Motegi Sei‐ichiro , Ohtsuki Mamitaro
Published: November 2024

Interleukin‐33 (IL‐33) is an alarmin released upon epithelial tissue damage. It functions as a nuclear factor for regulating gene expression. We hypothesised that IL‐33 is involved in the formation of decubitus ulcers through damaged epidermis. Therefore, this study aimed to clarify the mechanism of IL‐33 action in decubitus ulcer formation. IL‐33 knockout (KO), soluble stimulation‐2 (ST2) transgenic, and wild‐type (WT) mice were used to construct an ischemia–reperfusion (I/R) injury as a decubitus model. The ulcer area was significantly reduced in IL‐33 KO mice compared to WT mice but was not reduced in ST2 transgenic mice. Anti‐IL‐33 receptor (transmembrane ST2) antibodies effectively prevented ulcer formation; however, an anti‐IL‐33 neutralising antibody was ineffective. The number of infiltrating macrophages was higher, while that of neutrophils and mast cells was lower in IL‐33 KO mice than in WT mice. The number of M2 macrophages increased in IL‐33 KO mice. Characterisation of gene expression levels revealed significantly reduced interleukin‐1 beta (IL‐1β) and increased C‐C motif chemokine ligand 17 expression in IL‐33 KO mice. Macrophages isolated from ulcers in WT or IL‐33 KO mice stimulated with exogenous IL‐33 produced comparable amounts of IL‐1β. In conclusion, our study indicates that IL‐33 is released in response to I/R injury in the skin, contributing to inflammatory macrophage and mast cell infiltration and stimulation, resulting in IL‐1β production and the massive infiltration of effector cells, including neutrophils, which finally induces decubitus ulcer formation. These results suggest that suppressing IL‐33 expression could be beneficial for treating early‐phase decubitus ulcers.
The calcium‐sensing receptor alleviates endothelial inflammation in atherosclerosis through regulation of integrin β1‐NLRP3 inflammasome
Authors: Jiang Yunge , Xing Wenjing , Li Zhong , Zhao Defeng , Xiu Bingxu , Xi Yuhui , Bai Shuzhi , Li Xiaoxue , Zhang Zheqi , Zhang Weihua , Li Hongxia
Published: November 2024

Atherosclerosis (AS) is a chronic inflammatory disease of arteries. Endothelial inflammation is key to the initiation and development of AS. The calcium‐sensing receptor (CaSR) is expressed in endothelial cells (ECs) but its role in endothelial inflammation during AS remains unclear. This study focused on the involvement of CaSR in regulating endothelial inflammation and its underlying mechanisms, providing novel insights for AS therapy. Here, we observed that CaSR agonist NPS‐R568 significantly reduced atherosclerotic lesions and aortic inflammation in high‐fat diet (HFD)‐fed ApoE−/− mice, while enhancing the expression of CaSR in aortic tissues. In vitro, human umbilical vein endothelial cells (HUVECs) exposed to oxidized low‐density lipoprotein (oxLDL) at 20 μg·mL−1 triggered inflammation, as indicated by the upregulation of vascular cell adhesion molecule‐1 (VCAM‐1), interleukin (IL)‐6, and IL‐1β expression, along with increased adherence of THP‐1 or U937 cells to the HUVECs. Additionally, treatment with 20 μg·mL−1 oxLDL led to downregulation of CaSR expression in HUVECs. The administration of CaSR agonist NPS‐R568 or overexpression of CaSR in HUVECs resulted in a significant reversal of inflammation induced by oxLDL. Mechanistically, CaSR was found to mitigate NLRP3 inflammasome activation by downregulating the protein level of integrin β1. In conclusion, our study elucidates the beneficial role of CaSR in reducing endothelial inflammation in AS through the regulation of integrin β1 and the subsequent NLRP3 inflammasome. CaSR emerges as a promising target for potential therapeutic interventions in AS.
Influence of the Loading Frequency on Very High Cycle Fatigue Behavior of Structural Steels
Authors: Teixeira M. C. , Awd M. , Walther F. , Pereira M. V.
Published: November 2024

In ultrasonic fatigue tests, the VHCF properties can be determined in a reasonable time. Nevertheless, the high frequency can affect the fatigue behavior for some materials. This study investigated the fatigue capability of 34CrNiMo6 and 42CrMo4 steels, both of which find widespread applications in several mechanical components. These steels were carried out for conventional and ultrasonic fatigue tests under fully reversed testing conditions. A microplasticity strain amplitude was calculated, indicating an order of magnitude decreases around 10–100, when compared with the experimental results from low‐frequency tests. Cyclic strain rates were estimated for each steel and correlated with the number of cycles to failure. A conversion constant was obtained by fitting a curve to convert the high frequency results into theoretical results at low frequency. The experimental and predicted results were evaluated. The results proved the relevance of the strain rate in frequency effect. The converted results showed strong agreement with the experimental results in low‐frequency tests for the steels being studied.
Role of Loading Rate on Cracking Behavior in Granite Disks With Laboratory Experiments and Grain‐Based Modeling
Authors: Yang Yingming , Lei Ruide , Gu Qingheng , Hu Chao , Zhou Linsen , Wei Shirong , Li Xuejia
Published: November 2024

The investigation of the tensile properties of rock materials is essential for understanding the failure mechanism of engineering rock masses. In this study, we conducted a series of Brazilian splitting tests on granite specimens under three different loading rates, concurrently monitored using acoustic emission (AE) and digital image correlation (DIC) techniques. The results show that the mechanical parameters of granite disks are positively correlated with the loading rate. The AE waveforms are found to be associated with the lower frequency band, suggesting that this frequency range primarily dominates the failure mechanism in granite disks. Furthermore, the onset of micro‐tensile fractures precedes the development of micro‐shear ones. The elevation distribution of the fractured surfaces of the granite disks follows a Gaussian function. The fractal dimension increases progressively with the loading rate, whereas the complexity and irregularity of the fractured surface decrease. Moreover, the cracking mechanism of granite disks at the microscale was revealed using grain‐based modeling (GBM). The intergranular tensile cracks predominantly form along the radial direction, and the proportion of intergranular shear cracks is the smallest.
Characterisation of Five Natural Magnetite Reference Materials for In Situ Iron Isotope Measurement with Application to Magmatic Ni‐Cu Sulfide Mineralisation
Authors: Feng Yantong , Zhang Wen , Bao Yawen , Zeng Xianli , Liu Hong , Luo Tao , Hu Zhaochu , Zhang Mingjie , Wang Yu , Yang Yan , Liu Shengjiang
Published: November 2024

Iron isotope ratios in magnetite have been widely used to reveal critical geological and biological processes. Laser ablation multi‐collector inductively coupled plasma‐mass spectrometry (LA‐MC‐ICP‐MS) is ideally suited for measurement of Fe isotope ratios, however the lack of suitable reference materials poses a significant challenge for in situ Fe isotopic measurements in magnetites. In this study, five high‐quality natural magnetite crystals were characterised for Fe isotope ratios using solution nebulisation (SN)‐MC‐ICP‐MS and LA‐MC‐ICP‐MS. The effects of LA‐MC‐ICP‐MS analytical conditions were investigated to obtain precise and accurate Fe isotope ratios. The yielded intermediate measurement precisions for the δ56Fe values in the five investigated magnetites were ± 0.05–0.06‰ (2s) using SN‐MC‐ICP‐MS and ± 0.08–0.14‰ (2s) using LA‐MC‐ICP‐MS. Magnetites with homogeneous Fe isotopic compositions in hand‐specimen measurements and microanalysis can serve as potential reference materials for in situ Fe isotopic measurement. Furthermore, the Fe isotope ratios in the magnetites from the Jinchuan Ni‐Cu‐PGE sulfide deposit were measured using LA‐MC‐ICP‐MS with natural magnetite as the bracketing calibrator. The increase in the Fe isotopic composition with magmatic sulfide evolution was primarily dominated by oxygen fugacity (fO2) and hydrothermal fluids. This finding implies that the Fe isotopic composition of magnetite can serve as a potential geochemical indicator of magmatic Ni‐Cu sulfide mineralisation.
Knowledge and practices of nurses working in urology clinics on fluid–electrolyte monitoring and management
Authors: Seyhan Ak Ezgi , Culha Yeliz , Eren Esra , Ozbas Ayfer
Published: November 2024

The aim of the study was to examine the knowledge and practices of nurses working in urology clinics on fluid–electrolyte monitoring and management. The study sample for this descriptive cross‐sectional research comprised 79 nurses employed in clinics providing care to urology patients from June 2023 to June 2024. These nurses had internet access and consented to participate in the study on a voluntary basis. The data were obtained through the ‘Google Form’, which uses a descriptive characteristics form, a fluid–electrolyte monitoring and management knowledge form, and a practice form for fluid–electrolyte monitoring and management. The mean score of the nurses on the fluid–electrolyte monitoring and management knowledge form was 7.48 ± 1.74. The most common practice related to fluid–electrolyte monitoring and management was “I monitor and record additional fluid losses related to vomiting, diarrhoea, fever and drains”. When the mean scores of the fluid–electrolyte monitoring and management knowledge form were compared according to the individual characteristics of the nurses, no statistically significant difference was found between the mean scores of the knowledge form according to the characteristics of the nurses (p > 0.05). In this study, the mean knowledge scores of the nurses were above average. When the practices of the nurses for the prevention of fluid–electrolyte imbalances were examined, most of them stated that they monitored additional fluid losses related to vomiting, diarrhoea, fever and drains. The characteristics of the nurses (clinical experience, age, years of working in the profession and educational status) did not affect their knowledge scores.
How Infants Direct Their Gaze to Faces in the Presence of Other Objects: The Development of Face Preference Between 4 and 7 Months After Birth
Authors: Belteki Z. , Hessels R. S. , Junge C. M. M. , Kemner C. , van den Boomen C.
Published: November 2024

From early in development, infants process faces in their environment differentially from other items. By around 6 months of age, they are able to orient toward faces in the presence of distractor items. This paper aimed to assess whether this preferential looking toward faces was observable prior to 6 months of age, and whether there were developmental trends. We assessed this using the face pop‐out task, a free viewing eye‐tracking experiment in which infants viewed arrays containing an image of a face, alongside four distractor items. We assessed whether infants at 4, 5, 6 and 7 months (n = 1585 participants) differed in the proportion of first looks, total dwell time, and frequency of fixations to faces compared to other items. All three outcome variables were significantly higher toward faces than toward any of the other items in all the age groups. Moreover, there were age‐related differences across all measures—the older the infants were, the more pronounced their face preferences were. These age‐related differences could not be attributed to differences in data quality, and thus suggest that face preference is observable at 4 months of age but shows a strong development until 6 months.
Impact of Age and Comorbid Conditions on Incidence Rates of COVID‐19‐Associated Hospitalizations, 2020–2021
Authors: Saiman Lisa , Walsh Edward E. , Branche Angela R. , Barrett Angela , Alba Luis , Gollerkeri Sonia , Schillinger Julia A. , Phillips Matthew , Finelli Lyn
Published: November 2024

Background

COVID‐19‐associated hospitalization rates by age and comorbid conditions can more precisely assess risk for severe illness and target prevention and treatment strategies.

Methods

We performed a retrospective study to estimate population‐based COVID‐19‐associated hospitalization among patients by age and selected comorbid conditions in three hospital systems in Rochester and New York City (NYC), NY. Incidence rate ratios (IRR) comparing incidence rates for patients with and without these comorbidities were determined.

Results

From March 2020 to December 2021, 7779 patients were hospitalized with COVID‐19 of whom 43.8% had ≥3 comorbid conditions. Overall annual incidence ranged from 325.3 to 965.8 per 100,000 persons. Age group‐specific incidence was lowest in children 10–14 years (range 4.4–58.9) and highest in adults ≥85 years (range 2790.5–5889.6). Incidence rates for comorbid conditions generally increased with increasing age while IRR decreased with increasing age. Children in NYC 5–17 years with asthma or obesity had 3.4 and 53.3 times higher hospitalization rates, respectively, than children without these conditions. Adults in all age groups with obesity, diabetes, coronary artery disease, or congestive heart failure CHF had 1.6–4.7 times, 1.7–7.2 times, 2.0–10.1 times, or 1.7–20.2 times higher hospitalization rates, respectively, than those without these conditions. Adults ≥50 years with asthma had 1.5 to 1.8 times higher hospitalization rates than those without asthma.

Conclusions

The burden of hospitalization with COVID‐19 was high, particularly among adults ≥85 years and adults with obesity, diabetes, CAD, or CHF. However, the impact of comorbidities was less in older adults. Population‐based incidence rates by age and comorbidities provide more precise estimates of the benefits of vaccines and antiviral medications.
Alpha‐Ketoglutarate Alleviates Systemic Lupus Erythematosus–Associated Periodontitis in a Novel Murine Model
Authors: Mao Chuanyuan , Yu Weijun , Lin Lu , Yang Ruhan , Hu Shucheng , Li Guanglong , Gu Yuting , Jin Min , Lu Eryi
Published: November 2024

Aim

To establish a reproducible experimental animal model for systemic lupus erythematosus (SLE)‐associated periodontitis (PD), investigate the effects of SLE on PD and assess the therapeutic potential of alpha‐ketoglutarate (αKG) for SLE‐PD treatment.

Materials and Methods

An SLE‐PD murine model was established via ligature‐induced PD in MRL‐lpr strain, with MRL/MpJ strain as a non‐SLE control. The periodontal state was assessed using micro‐CT, real‐time PCR, histology, immunofluorescence and flow cytometry assays. αKG levels were analysed, and a thermoresponsive gel was designed as a periodontal dimethyl (DM)‐αKG delivery system. αKG levels were analysed in gingival crevicular fluid (GCF) of PD patients with or without SLE.

Results

SLE significantly increased the periodontal inflammation and bone resorption in the SLE‐PD model. αKG levels in GCF were lower in PD patients with SLE than in PD patients without SLE. Decreased αKG levels in the gingiva and macrophage M1/M2 imbalance were observed in SLE‐PD mice. However, DM‐αKG thermoresponsive gel effectively alleviated the periodontal inflammation, bone resorption and macrophage M1/M2 imbalance in SLE‐PD mice.

Conclusions

Our study established, for the first time, a novel SLE‐PD murine model and revealed that SLE increases the severity of PD in vivo. Our findings highlight the therapeutic potential of αKG for SLE‐associated PD.
Cross‐sectional association of irregular dietary habits with glycemic control and body mass index among people with diabetes
Authors: Shimizu Mika , Oya Junko , Kondo Yuichiro , Katamine Aki , Hasegawa Yukiko , Nakagami Tomoko
Published: November 2024

Aims/Introduction

To determine the association of irregular dietary habits with HbA1c and body mass index (BMI) in people with diabetes.

Materials and Methods

We included 4,421 people with diabetes aged 20–74 years (type 1 diabetes (T1D), 19.1%) who answered a questionnaire at mealtime. Adjusted least square means in HbA1c and BMI in patients with irregular dietary habits: “irregular mealtimes (irregular),” “skipping breakfast (SB),” and “late dinner (LD)” were compared to those with “regular dietary habits (regular).” Multivariable logistic regression analyses were performed to examine the association of irregular dietary habits with HbA1c ≥ 7% and BMI ≥25 kg/m2.

Results

HbA1c was significantly higher for “irregular” in both sexes and for “LD” in women than those of “regular” in people with T1D. HbA1c was significantly higher for “LD,” and BMI was higher for almost all irregular dietary habits than those of “regular” in people with type 2 diabetes (T2D). Odds ratios (ORs) for HbA1c ≥7% were 3.20 (95% confidence interval (CI), 1.30–7.89) for T1D women with “irregular” and 1.73 (1.20–2.49) and 2.20 (1.14–3.65) for T2D men and women with “LD,” respectively. ORs for BMI ≥25 kg/m2 were 1.60 (95% CI, 1.15–2.22) for T2D men with “irregular” and 1.43 (1.02–2.01) and 2.11 (1.21–3.65) for T2D women and men with “LD,” respectively.

Conclusions

Irregular mealtimes are associated with poor glycemic control in T1D women and are associated with obesity in T2D men. Furthermore, a late dinner was associated with high HbA1c levels and BMI in people with T2D.
Emotional bargaining after litigation: An experimental study of the Coase theorem
Authors: Chang Yun‐chien , Hung David Ta‐wei , Lin Chang‐Ching , Wang Joseph Tao‐yi
Published: November 2024

Entitlement assignment is unimportant if transaction cost is sufficiently low, as post‐litigation bargaining can redress allocative inefficiency, or so goes the Coase theorem. Ward Farnsworth, based on interviews with lawyers, argues that animosity created during litigation, a key mechanism to (re)allocate entitlement, will hinder the conclusion of any deal following litigation. Using a laboratory experiment, we test whether animosity generated before negotiations reduce the rate at which deals are successfully concluded and find evidence for a lower deal rate under one of the treatment conditions (the raw difference being three percentage points). The small practical effect may be attributed to rationality carrying the day and/or the limited degree of animosity we can generated in the lab with human subjects. The Coase theorem holds, while Farsworth's observation should not be ignored.
Cost Estimation for the Preservation of Selected Food/Crop Products With Ozone
Authors: Leeuwen J. van , Pandiselvam Ravi , Jeevarathinam G.
Published: November 2024

Most research publications on the application of ozone for the extension of shelf life of food and crop products suffer from, firstly, not clearly defining the dose of ozone used relative to the sample sizes of produce and, secondly, not quantifying the cost implication. The aim of this article is to clearly calculate the ozone dosage for some 30 different food storage applications. Then, a rationale for the cost estimation of ozonation on an industrial scale was established. The cost of ozonation was analyzed by separating the capital, operating and maintenance costs, and then expressing each of these as the cost per kg of applied ozone. This was done both for the use of ozone dissolved in water and for dry applications, where ozonated oxygen or air is applied to food products in a treatment chamber or directly in the storage area. Using the cost approaches as developed, it was shown that the most economical approach to generating ozone for all but small installations is to generate oxygen on‐site, thus using a smaller ozone generator and saving on power cost, ozone transfer, and maintenance. The estimated costs were applied to 30 research case studies on food preservation with ozone published in various journals. This covers seven on vegetable storage, eight on fruits, four on juices, five on meat and seafood, and five on stored grain. In summary, the cost of ozonation of food articles is less than $0.01/kg of fruit, vegetable, or meat product, and about $0.002/kg grain. Fruit juices require more ozone, and the cost could be $0.01‐$0.04 per liter.
Petrogenesis of the Scapolite‐Bearing Kongurblak Shear Zone, Chinese Southwestern Tianshan: Implications for Rock‐Buffered Fluid Flow Migration During Orogeny
Authors: Lü Zeng , Chen Zhenyu , Festa Andrea
Published: November 2024

In the lower Kongurblak River, Chinese SW Tianshan, scapolite was first found in a narrow shear zone (the Kongurblak shear zone, KSZ), consisting of variably mylonitized sedimentary rocks, including marble, meta‐sandstone and felsic–marly phyllonite. These rocks show varying scapolite textures and modes (from less than 1% to 15%), as a sporadic fine‐grained matrix phase, porphyroblasts with abundant inclusions, or blocky aggregates. The Cl content of scapolite (0.90–2.79 wt.%) varies between different rock types, which is higher in meta‐sandstone and marble than in felsic–marly phyllonite. Rare patchy lower Cl domains of scapolite and Ba zoning of K‐feldspar in meta‐sandstone and Cl zoning of porphyroblastic scapolite in marly phyllonite suggest pulsed fluid circulation. P–T estimates, thermodynamic modelling and mineral textures indicate scapolite formation through metasomatizing sodic feldspar and/or metamorphic reactions at amphibolite‐facies conditions (470°C°C–600°C and 3–7 kbar). These findings suggest the NaCl–CO2–H2O fluids in the KSZ stem from an external source, not from evaporitic horizons, at ~200 Ma by apatite U–Pb dating. The chlorinity and X (CO2) values of fluids, calculated based on the chemistry of the assemblage scapolite–biotite and T–X (CO2) diagrams, correlate well with specific rock types they traverse, which show different mineral modes and compositions, prograde reactions, structural permeability and host rock cavities. This indicates that the chemistry of medium‐grade infiltrative fluids in shear zones is strongly rock‐buffered, with crucial implications for orogenic metallogenesis in specific rock types. Evidence that the lithologies within the KSZ and their tectonometamorphic histories are distinct from those of the two bounding metamorphic units suggests they represent exotic sedimentary blocks transported over long distances within a large‐scale mélange, also providing new constraints on the tectonic collage of the Chinese SW Tianshan.
Neurofilament heavy phosphorylated epitopes as biomarkers in ageing and neurodegenerative disease
Authors: De Paoli Laura F. , Kirkcaldie Matthew T. K. , King Anna E. , Collins Jessica M.
Published: November 2024

From the day we are born, the nervous system is subject to insult, disease and degeneration. Aberrant phosphorylation states in neurofilaments, the major intermediate filaments of the neuronal cytoskeleton, accompany and mediate many pathological processes in degenerative disease. Neuronal damage, degeneration and death can release these internal components to the extracellular space and eventually the cerebrospinal fluid and blood. Sophisticated assay techniques are increasingly able to detect their presence and phosphorylation states at very low levels, increasing their utility as biomarkers and providing insights and differential diagnosis for the earliest stages of disease. Although a variety of studies focus on single or small clusters of neurofilament phosphorylated epitopes, this review offers a wider perspective of the phosphorylation landscape of the neurofilament heavy subunit, a major intermediate filament component in both ageing and disease.

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Non‐optimal cognitive offloading in schizophrenia in a prospective memory task: Influence of both metacognitive beliefs and cognitive effort avoidance
Authors: Décombe Amandine , Scarampi Chiara , Malleville Elora , Capdevielle Delphine , Gilbert Sam J. , Raffard Stéphane
Published: November 2024

Cognitive offloading refers to the use of physical action and the external environment to simplify mental demand. One form of this—intention offloading—involves the use of external reminders to support delayed intentions. Both beliefs of poor memory ability and a preference to avoid cognitive effort lead to offloading intentions rather than using internal memory. Schizophrenia is a population with deficits in prospective memory and to overcome this difficulty, neuropsychological interventions can propose external aids such as reminders. However, it is unknown what motivates individuals with schizophrenia to spontaneously use reminders. Twenty‐seven individuals with schizophrenia and twenty‐seven non‐clinical individuals were recruited to perform a prospective memory task, with two levels of difficulty, by deciding whether to use reminders or their internal memory. The proportion of reminder use, performance (hits and errors), subjective effort and metacognitive beliefs were recorded. The results show a non‐optimal use of reminders in the schizophrenia group: this group used more reminders than the non‐clinical group when the task was easy but did not increase reminder usage when the task became more difficult. Individuals with schizophrenia perceived the task to be more effortful than the non‐clinical individuals in the easy task, but also had a high estimation of their memory ability. Reminder usage in schizophrenia is atypical and non‐optimal. This may relate to effort and metacognition but the direct influence of these factors remains to be demonstrated. The overall results open perspectives on the neuropsychological treatment of prospective memory in this population.
The Efficacy of Topical Cosmetic Containing Alpha‐Arbutin 5% and Kojic Acid 2% Compared With Triple Combination Cream for the Treatment of Melasma: A Split‐Face, Evaluator‐Blinded Randomized Pilot Study
Authors: Tantanasrigul Pimpa , Sripha Apinya , Chongmelaxme Bunchai
Published: November 2024

Background

While the gold standard treatment for melasma is triple combination cream (TCC), arbutin and kojic acid demonstrate their benefits and may be used as an alternative.

Aims

To investigate the efficacy of cream containing alpha‐arbutin 5% and kojic acid 2% (AAK) compared with TCC for melasma treatment.

Patients/Methods

A split‐faced, randomized study was conducted among 30 participants with melasma, and all were randomized to receive AAK or TCC on each side of their face for 12‐week along with 4‐week follow‐up period. The melanin index (MI), modified Melasma Area Severity Index (mMASI), and physician global assessment (PGA) scores were used to measure the effectiveness of interventions. Recurrence of melasma after treatment discontinuation was evaluated by MI and mMASI. Patient satisfactions and adverse effects were also evaluated. In the analysis, the mean difference (MD) was used for MI and mMASI, while Wilcoxon signed‐rank test was for the PGA scores, adverse effects, and patient satisfaction.

Results

The MD of MI and mMASI scores were not different between groups (mMASI [p = 0.344] and MI [p = 0.268]). The PGA scores only showed improvement on the TCC‐treated side (p = 0.032). Compared to the AKK group, the subjects with TCC showed higher severity of recurrence (MI [p = 0.004] and mMASI [p = 0.045]). No difference in patient satisfaction score between the groups, but erythema and stinging were higher in the TCC group.

Conclusions

The AAK cream appeared to be effective for melasma treatment, highlighting a lower recurrent rate and fewer adverse events than standard therapy.

Trial Registration: thaiclinicaltrials.org: TCTR20230124004