bluuebunny/crossref_metadata_2025 huggingface dataset:
Real‐world assessment of the patient profile, clinical characteristics, treatment patterns, and outcomes associated with erythropoietic and X‐linked protoporphyria
Authors: Silver Samuel M. , Houghton Katherine , Hitchens Abby , Ansquer Valérie Derrien , Ciepielewska Malgorzata
Published: January 2025

Erythropoietic protoporphyria (EPP) and X‐linked protoporphyria (XLP) are rare genetic disorders. There are limited data regarding how these disorders are managed in real‐world settings. The aim of this study was to document the characteristics and treatment patterns among patients diagnosed with EPP or XLP in general real‐world settings in the United States. We, therefore, conducted a retrospective medical record review of patients diagnosed with EPP or XLP on or before July 1, 2020. Data were analyzed for patients with EPP (n = 299) and XLP (n = 91). Outcomes included demographic and clinical characteristics, diagnostic testing, therapy recommendations, office visits, emergency department visits, and hospitalizations. Costs were assigned to healthcare resources. Mean (standard deviation [SD]; median) time between the first symptom documented in the medical records and diagnosis was 2.9 (5.1; 1.3) years. The most common pre‐diagnostic tests were liver function, total plasma and erythrocyte protoporphyrin, genetic tests, and renal function. Patients were advised to use sunscreen (85%) or modify their lifestyle (83%). Within 12 months of diagnosis, the mean (SD; median) number of office visits, emergency department visits, and inpatient hospitalizations related to EPP or XLP were 4.0 (3.5; 3.0), 0.8 (1.6; 0), and 0.4 (1.3; 0), respectively. Patients with EPP or XLP have several unmet needs, including timely and accurate diagnosis, symptom relief, and efficacious prevention of phototoxic reactions.
A global synthesis of the ecological effects of co‐invasions
Authors: Ahmad Rameez , Lone Showkeen A. , Rashid Irfan , Khuroo Anzar Ahmad
Published: January 2025

Globally, the majority of ecosystems are being invaded by multiple co‐occurring alien species. While most of the quantitative syntheses have focused on single invasive species impacts, a global‐scale quantitative synthesis on the interaction effects of species co‐invasions across multiple taxa and levels of ecological organization remain largely unexplored.

We address this knowledge gap by synthesizing quantitative information from 256 effect sizes published in 36 studies, that reported the individual and interaction effects of co‐occuring alien plant and animal species.

Although, our meta‐analysis showed that the mean interaction effect of co‐invasions across a range of variables was antagonistic (i.e. combined effect less than the sum of individual effects), the vote‐counting revealed additive interaction effects (i.e. combined effect equal to the sum of individual effects) to dominate individual observations. Also, the frequency of interaction effect types varied significantly with response variables, ecological organization, ecosystems, continents and study design, thereby indicating the role of these ecological characteristics in shaping co‐invasion interaction effects.

Synthesis. Overall, our synthesis highlights the need for incorporating local ecological complexities in future co‐invasion impact research to better predict their interaction effect on biodiversity and ecosystem functioning across spatio‐temporal scales. Looking ahead, we call for concerted research efforts on the ecological impacts of co‐invasions to unravel the causes of variability in interaction outcomes.
Sirt6, Deubiquitinated and Stabilised by USP9X, Takes Essential Actions on the Pathogenesis of Experimental Autoimmune Myasthenia Gravis by Regulating CD4+ T Cells
Authors: Xie Chen , Zhang Hong‐Lian , Yuan Jun , Zhang Ye , Liu Yang‐Chun , Xu Quan , Chen Li‐Ru
Published: January 2025

Myasthenia gravis (MG) presents with symptoms that significantly affect patients' daily lives. Long‐term MG therapies may lead to substantial side effects, predominantly due to prolonged immune suppression. Sirt6, which plays a vital role in maintaining cellular homeostasis and is recognised for its involvement in cytokine production in immune cells, has not yet been explored in relation to MG. PBMCs and CD4+ T cells were isolated from blood samples. RT‐qPCR, western blot and ELISA were used to assess the expression of target genes and proteins. Flow cytometry was used to identify the subsets of T helper cells. Co‐IP was conducted to investigate the interaction between USP9X and Sirt6. Finally, the experimental autoimmune myasthenia gravis (EAMG) model was established. In MG patients, Sirt6 levels were downregulated compared to healthy controls. Sirt6 overexpression led to a reduction in Th1 and Th17 cell populations while augmenting Treg cells in PBMCs. USP9X interacted with Sirt6, leading to its deubiquitination and stabilisation. Elevated Sirt6 levels subsequently mitigated symptoms in the EAMG model. The stabilisation of Sirt6, mediated by USP9X, has been found to relieve symptoms of EAMG by influencing the subtypes of T helper cells. This highlights the promising potential of Sirt6 as a viable therapeutic target in the treatment of MG.
Characterization of sulfakinin and its role in larval feeding and molting in Spodoptera frugiperda
Authors: Yu Ming‐Qing , Linghu Jun‐Hong , Xie Hua‐Yan , Li Gang , Zhu Feng , Smagghe Guy , Gui Shun‐Hua , Liu Tong‐Xian
Published: January 2025

Feeding and molting are particularly important physiological processes for insects, and it has been reported that neuropeptides are involved in the nervous regulation of these 2 processes. Sulfakinin (SK) is an important neuropeptide that is widely distributed among insects and plays a pivotal role in regulating feeding, courtship, aggression, and locomotion. In this study, we investigated the involvement of SK in feeding and molting on a highly notorious pest insect, the fall armyworm, Spodoptera frugiperda. SK transcript levels were found in all larval stages and there was a predominant expression of SK in the brain of 5th instar larvae. By immunostaining, SK was detected in 2 pairs of cells in the median protocerebrum. But during prolonged periods of starvation, there was a significant reduction in SK messenger RNA levels; however, subsequent refeeding led to a notable increase. To investigate the role of SK in feeding and molting, SK was silenced in S. frugiperda larvae through RNA interference. This resulted in a significant increase in food intake, weight gain, and the molting process happened more rapidly in the double‐stranded SK‐treated larvae compared to the controls. Conversely, injection of sulfated SK peptide (sSK) caused opposite effects. Interestingly, SK‐knockdown in larvae resulted in increased levels of 20‐hydroxyecdysone and also of the expression of some of it signaling pathway genes. Altogether, this study highlights the important role played by SK in regulating feeding and molting in S. frugiperda.
DeepQA: A Unified Transcriptome‐Based Aging Clock Using Deep Neural Networks
Authors: Qi Hongqian , Zhao Hongchen , Li Enyi , Lu Xinyi , Yu Ningbo , Liu Jinchao , Han Jianda
Published: January 2025

Understanding the complex biological process of aging is of great value, especially as it can help develop therapeutics to prolong healthy life. Predicting biological age from gene expression data has shown to be an effective means to quantify aging of a subject, and to identify molecular and cellular biomarkers of aging. A typical approach for estimating biological age, adopted by almost all existing aging clocks, is to train machine learning models only on healthy subjects, but to infer on both healthy and unhealthy subjects. However, the inherent bias in this approach results in inaccurate biological age as shown in this study. Moreover, almost all existing transcriptome‐based aging clocks were built around an inefficient procedure of gene selection followed by conventional machine learning models such as elastic nets, linear discriminant analysis etc. To address these limitations, we proposed DeepQA, a unified aging clock based on mixture of experts. Unlike existing methods, DeepQA is equipped with a specially designed Hinge‐Mean‐Absolute‐Error (Hinge‐MAE) loss so that it can train on both healthy and unhealthy subjects of multiple cohorts to reduce the bias of inferring biological age of unhealthy subjects. Our experiments showed that DeepQA significantly outperformed existing methods for biological age estimation on both healthy and unhealthy subjects. In addition, our method avoids the inefficient exhaustive search of genes, and provides a novel means to identify genes activated in aging prediction, alternative to such as differential gene expression analysis.
Exploring diagnostic stewardship in the emergency department evaluation of pediatric abdominal pain in a statewide quality collaborative
Authors: Janke Alexander T. , Michelson Kenneth A. , Kocher Keith E. , Seiler Kristian , Macy Michelle L. , Nypaver Michele , Mahajan Prashant V. , Arora Rajan , Mangus Courtney W.
Published: January 2025

Background

Diagnostic stewardship is the effort to optimize diagnostic testing to reduce errors while avoiding overtesting and overtreatment. Abdominal pain and appendicitis in children are essential use cases. Delayed diagnosis of appendicitis can be dangerous and even life‐threatening, but overtesting is harmful.

Methods

We conducted a retrospective cohort study of children aged 5–17 years presenting with abdominal pain to 26 EDs within the Michigan Emergency Department Improvement Collaborative (MEDIC) from May 1, 2016, to February 29, 2024. We defined two outcome measures summarized by ED. First, we describe the cross‐sectional imaging:appendicitis visits ratio, defined as the count of ED visits resulting in any cross‐sectional imaging (CT or MRI) divided by the count of ED visits with a diagnosis of appendicitis. Second, we describe the delayed diagnosis rate, defined by an ED visit for abdominal pain resulting in a discharge and subsequent return visit with a diagnosis of appendicitis within 7 days.

Results

The sample included 120,112 pediatric visits for abdominal pain at 26 EDs; 4967 (4.1%) were diagnosed with appendicitis. The cross‐sectional imaging:appendicitis visits ratio varied by site, from as low as 0.2 (95% confidence interval [CI] 0.1–0.2) at a pediatric site to as high as 7.9 (95% CI 4.8–16.4) at an urban ED. The proportion of pediatric ED visits for abdominal pain that resulted in an identified delayed diagnosis of appendicitis was 0.1% (141/120,112). All but four sites had fewer than 10 cases of delayed diagnosis across the study period.

Conclusions

In this retrospective cohort study of 120,000+ ED visits for pediatric abdominal pain, we found that the ratio of visits with cross‐sectional imaging to diagnosed cases of appendicitis varied widely across EDs. Delayed diagnosis of appendicitis was uncommon. Adherence to best practices and improved imaging quality may hold promise to improve diagnostic stewardship for children with abdominal pain across EDs.
Decreased racial disparities in sepsis mortality after an order set–driven initiative: An analysis of 8151 patients
Authors: Fernandez Olivera Maria L. , Pafford Carl , Lardaro Thomas , Roumpf Steven K. , Saysana Michele , Hunter Benton R.
Published: January 2025

Background

Sepsis is a leading cause of hospital mortality and there is evidence that outcomes vary by patient demographics including race and gender. Our objectives were to determine whether the introduction of a standardized sepsis order set was associated with (1) changes in overall mortality or early antibiotic administration or (2) changes in outcome disparities based on race or gender.

Methods

Patients seen in the emergency department and admitted to the hospital with a diagnosis code of sepsis were identified and divided into a preintervention cohort seen during the 18 months prior to the initiation of a new sepsis order set and an intervention cohort seen during the 18 months after a quality initiative driven by introducing the order set. Associations between time period, race, gender, and mortality were assessed using univariate and multivariate logistic regression models. Other outcomes included early antibiotic administration (<3 h from arrival).

Results

Overall mortality was unchanged during the intervention period (7.8% vs. 7.2%) in both univariate (relative risk [RR] 1.08, 95% confidence interval [CI] 0.93–1.26) and multivariate logistic regression (RR 1.11, 95% CI 0.93–1.28) models. Although male gender tended to have higher mortality, there was no statistically significant association between gender and mortality in either cohort. In the multivariable model, Black race was associated with increased risk of death in the preintervention period (RR 1.41, 95% CI 1.02–1.94), but this association was not present in the intervention period. Patients of color also saw significantly more improvement in early antibiotic administration during the intervention period than White patients.

Conclusions

An order set–driven sepsis initiative was not associated with overall improved mortality but was associated with decreased racial disparities in sepsis mortality and early antibiotics.
Hypereosinophilia and Hypereosinophilic Syndromes: First Findings From a Nationwide Multicenter Cohort
Authors: Lefèvre Guillaume , Bleuse Séverine , Puyade Mathieu , Moulis Guillaume , Néel Antoine , Abisror Noémie , Baudet Antoine , Bonnotte Bernard , Dion Jérémie , Dossier Antoine , Grall Maximilien , Lifermann François , Limal Nicolas , Lioger Bertrand , Machelart Irène , Mohr Catherine , Outh Roderau , Queyrel‐Moranne Viviane , Slama Borhane , Tréfond Ludovic , Abou Chahla Wadih , Ackerman Félix , Belfeki Nabil , Berezne Alice , Blade Jean‐Sébastien , Bouderbala Mohammed Azzedine , Chebrek Safia , Cottin Vincent , De Almeida Sébastien , De Masson Adèle , Dezoteux Frédéric , Goulenok Tiphaine , Jachiet Vincent , Jouvray Mathieu , Latu Irina , Ledoult Emmanuel , Leurs Amélie , Lugosi Maxime , Martin Michael , Melboucy‐Belkhir Sara , Morati‐Hafsaoui Chafika , Quemeneur Thomas , Rohmer Julien , Roy‐Peaud Frédérique , Sanges Sébastien , Schleinitz Nicolas , Staumont‐Salle Delphine , Taillé Camille , Terriou Louis , Tieulie Nathalie , Koenga Japhete Darline Elenga , Schwarb Laurent , Panel Kewin , Kahn Jean‐Emmanuel , Groh Matthieu ,   the COHESion study group
Published: January 2025

Background

Hypereosinophilic syndromes (HES) are a heterogenous group of eosinophilic disorders. To date, only retrospective studies of limited sample‐size and/or follow‐up duration are available.

Methods

The COHESion study is a national prospective multicenter multidisciplinary cohort recruiting both adults or children with the spectrum of eosinophilic disorders (including reactive HE/HES [HE/HES‐R], idiopathic HES [HES‐I], lymphocytic HES [HES‐L], neoplastic HE/HES [HE/HES‐N], HE of unknown significance [HE‐US], as well as IgG4‐related disease [IgG4RD] or ANCA‐negative eosinophilic granulomatosis with polyangiitis [EGPA] overlaps). Patients are followed‐up yearly. All data about final diagnosis, organ involvement assessments, and outcome profiles in HES‐I were captured and analyzed centrally by HES expert centers.

Results

From May 2019 to November 2023, 779 patients were included. For this preliminary analysis, 550 cases were available for centralized review (mean ± SD age: 56 ± 18 years, 42% of female patients). The final diagnoses were HES‐I (47%), HE/HES‐R (16%), HE‐US (15%), HE/HES‐N (7%), HE/HES‐L (6%), IgG4RD (2%), and ANCA‐negative EGPA (7%). In the 258 HES‐I patients, outcome profiles were classified as follows: 16.3% had a “single‐flare” without further relapse, 28.3% had a “relapsing–remitting” disease when there was at least a 6‐month period free of symptoms between two flares, 46.1% had a “persistent disease” requiring continuous treatment to avoid relapses (9.3% remained unclassified because of insufficient follow‐up).

Conclusions

The COHESion cohort is the first nationwide prospective multicenter study collecting data on the full spectrum of HE/HES disorders. This preliminary analysis confirms that idiopathic HES patients have various outcome profiles, suggesting different underlying pathophysiological mechanisms and the need of patient‐specific management.

Trial Registration

ClinicalTrials.gov identifier: NCT 04018118
Should adolescents and young adults with Hodgkin lymphoma be treated as children or adults?
Authors: Lew‐Derivry Lucille , Chevillon Florian , Brice Pauline , Bigenwald Camille , Landman‐Parker Judith , Leblanc Thierry , Boissel Nicolas , Cabannes‐Hamy Aurélie
Published: January 2025

Hodgkin lymphoma (HL) is one of the most common cancers in adolescents and young adults (AYA). Paediatric and adult therapeutic strategies diverge while sharing the common objective: maintaining optimal efficacy with less long‐term toxicity. However, few studies have compared the outcome of AYA treated according to one or the other approaches. Among the 148 patients aged 15–25 years, treated at Saint‐Louis Hospital for newly diagnosed HL between 2012 and 2018, 71 were treated according to an adult protocol and 77 were treated according to a paediatric one. The 5‐year overall survival (OS) and progression‐free survival (PFS) were, respectively, 100% and 85%, with no significant difference between treatment groups (85% in paediatric vs. 86% in adult, p = 0.7). Overall, the 5‐year PFS was 100% for early favourable stages and 78% for advanced stages. A higher risk of short‐term steroid and vincristine‐related toxicities was observed in paediatric regimen, whereas a higher risk of late toxicities was expected in adult regimen, due to higher anthracyclines, procarbazine, bleomycin and radiotherapy exposure. These results confirm the excellent outcome of AYA patients with HL, whatever the treatment strategies. They justify a tailor‐made therapeutic decision and highlight the importance of managing AYA patients in dedicated units with trained professionals.
Physiological change in ganglion cell inner plexiform layer and nerve fibre layer thickness over six years
Authors: Soh Zhi‐Da , Yu Marco , Chen Yanyan , Thakur Sahil , Lavanya Raghavan , Tham Yih Chung , Koh Victor , Aung Tin , Cheng Ching‐Yu
Published: January 2025

Background

To evaluate the 6‐year physiological rates‐of‐change in ganglion cell inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) thickness measured with optical coherence tomography.

Methods

We included 2202 out of 2661 subjects from the population‐based Singapore Chinese Eye Study who returned for follow‐up 6 years after baseline examination (follow‐up rate 87.7%). OCT scans with signal strength (SS) <6, imaging errors, and ocular pathologies were excluded. A linear mixed model was used to measure the rates‐of‐change in GCIPL and RNFL thickness. Time and difference between baseline and follow‐up scan SS were modelled as fixed effect. Baseline age, baseline measurement, gender, hypertensive medication, diabetes status, cardiovascular disease, smoking status, body mass index, spherical equivalent (SE), intraocular pressure and optic disc area were each analysed in an interaction term with time.

Results

The adjusted mean rate‐of‐change in average GCIPL was −0.312 μm/year in males and −0.235 μm/year in females. Older age and thicker GCIPL thickness at baseline were associated with higher rates‐of‐change while females and more hyperopic SE were associated with lower rates‐of‐change. The adjusted mean rate‐of‐change in average RNFL was −0.374 μm, with higher rates‐of‐change in the vertical quadrants and no differences between genders. Older age and thicker RNFL thickness at baseline were associated with higher rates‐of‐change in average RNFL and RNFL thickness in the vertical quadrants, and vice versa for each unit increase in scan SS and SE.

Conclusion

Our population cohort provides data on physiological thinning of GCIPL and RNFL with age. Differentiating physiological changes in GCIPL and RNFL is important for more accurate clinical assessment.
Effectiveness and safety of iGlarLixi in people with type 2 diabetes not at target on basal insulin and oral antidiabetic therapy in a prospective observational trial
Authors: Seufert Jochen , Wiesner Tobias , Pegelow Katrin , Kenzler Julia , Pfohl Martin
Published: January 2025

Aims

This study assessed efficacy and safety of the fixed ratio combination iGlarLixi 100/33 (insulin glargine 100 U/mL plus lixisenatide 33 μg/mL) in people with type 2 diabetes (PwT2D) in daily clinical practice.

Materials and Methods

This non‐interventional, multicentre, prospective, single‐arm 24‐week study documented PwT2D with an HbA1c of 7.5%–10.0%, currently treated with a basal insulin supported oral therapy (BOT) in German primary care facilities, after the physician had decided to change treatment to iGlarLixi 100/33, independent of study participation. Primary end‐point was the absolute change in HbA1c (%) from baseline.

Results

Of 93 participants included, 70 comprised the full analysis set for efficacy assessment. Approximately 24 weeks after switching to iGlarLixi 100/33 HbA1c (mean ± standard deviation) changed from 8.52 ± 0.82% by −0.74 ± 0.81% to 7.74 ± 0.76%, FPG from 174.3 ± 44.6 mg/dL (9.67 ± 2.48 mmol/L) by −32.9 ± 46.3 mg/dL (−1.83 ± 2.57 mmol/L) to 141.4 ± 34.1 mg/dL (7.85 ± 1.89 mmol/L) and body weight from 104.3 ± 22.5 kg by −3.0 ± 7.5 kg to 101.3 ± 21.6 kg (all p < 0.01). Furthermore, use of DPP4 inhibitors was significantly reduced from 34.8% to 6.8% of participants. Derived (from 7‐point self‐measured plasma glucose) time in range (TIR) increased and time above range (TAR) decreased after 24 weeks to target ranges (all p < 0.05). Flash glucose monitoring data of 20 patients showed similar patterns for TIR and TAR, respectively, and a reduction in time below range (p = 0.007). Hypoglycaemia events did not change significantly and were low in number. No severe hypoglycaemia was reported.

Conclusions

Modifying antiglycaemic treatment from a BOT regimen to iGlarLixi 100/33 in suboptimal controlled PwT2D in daily clinical practice improved glycaemic control without increasing hypoglycaemia and with favourable body weight change.
SARS‐COV‐2 Pre‐Exposure Prophylaxis With Tixagevimab‐Cilgavimab in Haematological, Immunocompromised Patients in the Omicron Era
Authors: Hoechstetter Manuela A. , Hollwich Eva‐Maria , Illner Doris , Pham Thu‐Trang , von Bergwelt‐Baildon Michael , Dreyling Martin , Wendtner Clemens‐Martin
Published: January 2025

Background

Pre‐exposure prophylaxis with tixagevimab‐cilgavimab significantly reduced severe COVID‐19 outcomes in high‐risk individuals during the pre‐Omicron era (PROVENT trial). However, efficacy in patients with haematological malignancies (HM) was underreported. The rapid emergence of Omicron strains in 2021 showed reduced neutralizing activity in preclinical data, but real‐world data remains limited due to short follow‐up.

Patients and Methods

We aimed to evaluate the effectiveness and safety of tixagevimab‐cilgavimab in 86 HM patients during the early Omicron wave, including the BA.2, BA.5, and XBB.1 sublineages.

These patients received PrEP between February and August 2022 due to impaired vaccine response (72%) and B‐cell depletion (46.5%). They were followed prospectively until April 2023, with a median follow‐up of 297 days.

Results

Breakthrough SARS‐CoV‐2 infections occurred in 32.6% of patients, with 22.1% within six months. Infections within six months were milder and shorter. B‐cell depletion within six (p = 0.035) and twelve months (p = 0.016) was identified as risk factor for breakthrough infections. No new safety events were reported.

Conclusion

Our data showed that tixagevimab‐cilgavimab prophylaxis effectively reduces severe COVID‐19 outcomes in patients with HM, particularly within the first six months, even during the Omicron era. However, those with recent B‐cell depletion (within 12 months) remained at high risk.
A house is more than a home: Why the law should discourage the shift to renting and the effects of the shift on nascent families
Authors: Sabbagh Lucas
Published: January 2025

“Generation Rent” is a term that denotes the trend of young people renting as opposed to buying housing. This, in part, is due to rising housing prices. This Note seeks to look at the potential effects of private “pushes” for an increase in renting and in the private equity firm ownership of Single‐Family Rentals. There are many negative tradeoffs between renting and homeownership in relation to family wealth over a long term. Several proposed solutions to this problem include using Tax Deductions to encourage buying and using Eminent Domain to attack concentrated housing ownership.
Tree Lifespans in a Warming World: Unravelling the Universal Trade‐Off Between Growth and Lifespan in Temperate Forests
Authors: Liu Shuhui , Brienen Roel J. W. , Fan Chunyu , Hao Minhui , Zhao Xiuhai , Zhang Chunyu
Published: January 2025

Tree growth and lifespan are key determinants of forest dynamics, and ultimately control carbon stocks. Warming and increasing CO2 have been observed to increase growth but such increases may not result in large net biomass gains due to trade‐offs between growth and lifespan. A deeper understanding of the nature of the trade‐off and its potential spatial variation is crucial to improve predictions of the future carbon sink. This study aims to identify key drivers of growth and lifespan, assess the universality of tree growth‐lifespan trade‐offs, explore the possible latitudinal patterns of trade‐off strengths and their determinants, and project growth and lifespan under future climate scenarios. We analyzed 21,193 trees of 69 species (48 included in further analysis) at 445 sites (417 included in further analysis) in temperate forests in northeastern China to estimate early growth rate and tree lifespan. We find that temperature and human pressure enhance tree growth and reduce lifespan, while altitude increases lifespan. We further find evidence for growth‐lifespan trade‐offs at all studied levels, that is, among trees, among species and communities, and within species and communities. Trade‐offs are stronger at colder, higher latitudes compared to warmer sites, because of larger variation in tree growth and climate, larger range sizes for individual species, and lower species' diversity for communities at high latitudes. We predict future increases in growth and reductions in tree lifespan in response to climate change for the 2050s. Taking growth lifespan trade‐offs into account resulted in even larger predictions of decreases in tree lifespan of up to 8%. In conclusion, growth‐lifespan trade‐offs are universal, but the strengths may vary by environment and between different forests. Its effects are important to include in predictions of forest responses to global change and need to be considered more widely.
Amitriptyline for the treatment of vulvodynia in patients with vulvar lichen sclerosus: a case series of 20 patients
Authors: Licata Gaetano , Di Brizzi Eugenia Veronica , Tancredi Vittorio , Arisi Mariachiara , Ariasi Cesare , Giorgio Caterina Mariarosaria
Published: January 2025

Vulvar Lichen Sclerosus (VLS) is a chronic autoimmune disease that often leads to vulvodynia, a debilitating chronic pain condition in the vulvar region. Treating vulvodynia in the context of VLS presents a significant therapeutic challenge due to the lack of standardized protocols. This article presents a case series of 20 women treated with amitriptyline for vulvodynia secondary to VLS, accompanied by an extended review of the literature. The results suggest that amitriptyline may offer significant pain relief and improvements in the patients’ quality of life, although adverse effects need to be carefully managed. Further studies are needed to validate these findings in larger controlled trials.
The use of submaximal parameters in the assessment of exercise capacity in children with obesity
Authors: Peled K. , Kodesh Einat , Zucker‐Toledano Merav , Bar‐Yoseph R. , Borik‐Chiger S. , Mainzer Gur
Published: January 2025

Background

Peak oxygen uptake (VO2) is considered the most important indicator of aerobic exercise capacity during cardiopulmonary exercise testing (CPET). However, its accuracy is compromised when maximal effort is not achieved. In such cases, submaximal parameters can serve as surrogates for assessing exercise performance.

Objectives

To compare the differences in maximal and submaximal exercise parameters between children with obesity and normal weight.

Methods

A prospective study evaluating CPET using a treadmill completed by children with and without obesity.

Results

A total of 153 children (50.9% females) were divided into two groups: obese (n = 87) and non‐obese (n = 66). Children with obesity achieved lower exercise capacity (peakVO2 of 68% ± 16% vs. 89% ± 15%; p < 0.0001) with fewer achieving maximal effort (26.4% vs. 78.7%, respectively). VO2‐derived submaximal parameters showed a significantly lower oxygen uptake efficiency slope per body weight (OUES/kg) (30.5 ± 6.1 vs. 39.0 ± 9.5; p < 0.0001) and lower VO2 at ventilatory threshold (VO2@AT) (21.2 ± 4.6 vs. 26.4 ± 5.3, p = 0.0001) in the obese group, with no significant differences in the CO2‐derived parameters.

Conclusions

Maximal exercise data in children with obesity is frequently unavailable due to failure to achieve maximal effort. Submaximal parameters, such as OUES and VO2@AT, may be useful substitute options for assessing the health and functional level of this population.
High‐temperature subcritical crack growth in a 3D woven SiC‐based composite
Authors: Kanazawa Shingo , Ikarashi Yoshito , Ogasawara Toshio , Fukuhara Satoru , Kubushiro Keiji , Aoki Takuya , Zok Frank W.
Published: January 2025

This study investigates the subcritical crack growth behavior of a 3D woven SiC‐based composite under cyclic loading at 1100°C in air. The composite was subjected to monotonic tension and tension–tension fatigue tests using both unnotched dumbbell‐shaped and edge‐notched specimens. Detailed examinations of crack growth were conducted through optical microscopy and X‐ray computed tomography (XCT). While the monotonic tensile strength was found to be insensitive to millimeter‐sized notches, the fatigue strength was reduced by 20%–30% in the presence of such notches. Crack growth was found to be irregular and chaotic at the mesoscale, influenced by the complex interplay of chemical and mechanical processes and spatial variability in the composite microstructure. The study emphasizes the importance of XCT imaging for accurate internal crack tracking. It also proposes a phenomenological fracture mechanics model to describe crack growth and lifetime prediction, highlighting the nonmonotonic nature of crack growth rates.
Association of Cardiac CT‐Derived Epicardial Adipose Tissue With Atrial Fibrillation in Patients Without Left Atrial Fibrosis as Defined by Endocardial Voltage Mapping
Authors: Umar Aqeel , Hocking Jeffrey , Massin Sophia Z. , Suszko Adrian , Wintersperger Bernd J. , Chauhan Vijay S.
Published: January 2025

Introduction

Epicardial adipose tissue (EAT) is often associated with atrial fibrosis, and both can provide the substrate for atrial fibrillation (AF). However, most AF patients have no evidence of left atrial (LA) fibrosis based on bipolar voltage mapping. We determined whether EAT differs in AF patients without LA fibrosis compared to matched controls without AF.

Methods

Patients undergoing cardiac CT before first‐time AF catheter ablation were prospectively enrolled. LA bipolar voltage mapping was performed, and patients were divided into ‐LVZ (LA low voltage zones < 5% of LA surface area; no fibrosis) and +LVZ (LA low voltage zones ≥ 5%; fibrosis). A control group without AF was matched to −LVZ patients. EAT was quantified on CT using standard signal thresholding to quantify total and regional volumes. AF patients were followed for 1‐year postablation to assess atrial arrhythmia (AA) recurrence.

Results

−LVZ (n = 50) had higher total EAT volumes than matched controls (n = 48) (79 [58–109] vs. 51 [37–73] cm³, p < 0.001), higher LA EAT (9 [6.3–12] vs. 4.2 [2.9–5.8] cm³, p < 0.001), higher posterior LA EAT (9.7 [6.4–12] vs. 5.9 [2.8–7.2] cm³, p < 0.001) and higher right atrial EAT (7.3 [5.1–9.9] vs. 4.8 [3.2–6.5] cm³, p < 0.001). These differences remained even after correcting EAT for BMI and LA volumes. There were no significant differences in EAT volumes between −LVZ and +LVZ (n = 25). There was no significant association between EAT and AF recurrence postablation.

Conclusion

EAT volume is greater in AF patients without evidence of LA fibrosis compared to matched controls without AF. These findings support an association of EAT with AF pathogenesis even in the absence of LA fibrosis.
Periodontal Care Is Associated With a Lower Risk of Dialysis Initiation in Middle‐Aged Patients With Type 2 Diabetes Mellitus: A 6‐Year Follow‐Up Cohort Study Based on a Nationwide Healthcare Database
Authors: Kusama Taro , Tamada Yudai , Osaka Ken , Takeuch Kenji
Published: January 2025

Objective

To investigate the association between dental attendance with periodontal care and the risk of dialysis initiation in patients with type 2 diabetes mellitus (T2D).

Methods

This retrospective cohort study used data from the Japan Medical Data Center (JMDC) claims database (January 2015 to August 2022). Patients with T2D, aged 40–74, were included. Dental attendance with periodontal care and initiation of dialysis were used as the exposure and outcome variables, respectively. We fitted the Cox proportional hazards model, including potential confounders, to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs).

Results

Among 99,273 participants (mean age = 54.4 years [SD = 7.8], male = 71.9%), the incidence rate of dialysis initiation was 0.92 per 1000 person‐years. After adjusting for all covariates, those with periodontal care (HR = 0.68 [95%CI = 0.51–0.91] for ≥ 1 time/year and HR = 0.56 [95%CI = 0.41–0.77] for ≥ 1 time/6 months) had a significantly lower risk of dialysis initiation compared to those without dental attendance.

Conclusion

Periodontal disease care in patients with T2D is associated with a reduced risk of dialysis initiation by 32%–44%. This suggests that integrating periodontal care into diabetes management may help prevent the progression of diabetic nephropathy and improve patient outcomes.
Substituting the Conventional Facebow With an Extraoral Scan Body System for Transferring the Maxillary Cast Into the Virtual Articulator: Manufacturing Procedures and Digital Clinical Protocol
Authors: Revilla‐León Marta , Zeitler Jonathan M. , Kois John C.
Published: January 2025

Clinical Considerations

Conventional facebow records are used to transfer the maxillary cast into the analog articulator. Different reference planes have been described, including the true horizontal or gravity reference plane. A conventional facebow (Kois Dentofacial Analyzer; Panadent) allows the recording of the gravity plane for transferring the maxillary cast into the analog semi‐adjustable articulator. Clinical procedures should also allow the maxillary scan transfer into the virtual articulator by using the true horizontal reference plane.

Objective

The present manuscript describes the step‐by‐step protocol to record the gravity plane and to transfer the maxillary scan into the virtual articulator by using an extraoral scan body system.

Conclusions

The extroral scan body device enables the substitution of the conventional facebow procedure. Additionally, this extraoral scan body is fabricated by using additive manufacturing technologies and eases the complete digital workflow for transferring the maxillary scan into the virtual articulator.
The Influence of Surface Treatment on the Color of Enamel and Dentin: An In Vitro Study Using Machine Learning‐Based Analysis
Authors: Wang Zhen‐Yu , Hu Fei‐Yu , Wu Chao‐Qiang , Liu Fei , Chen Du , Shen Jun‐Fei , Shen Jie‐Fei
Published: January 2025

Objective

To investigate how surface treatment affects the color of enamel and dentin, and to evaluate whether the color differences are acceptable.

Materials and Methods

Freshly extracted premolars were prepared using diamond burs (blue, red, and yellow tapes). Tooth surfaces were divided into control and acid‐etched areas and treated with phosphoric acid (5, 15, 30, 45, and 60 s). Adhesives were applied and light‐cured. Hyperspectral images were captured to analyze reflectance spectra, calculating L, a, b, and ΔE2000 values under the D65 illuminant. Enamel and dentin slices underwent atomic force microscopy for surface roughness. A random forest model was trained to assess the effects of multiple factors on color differences. Statistical analyses included one‐way ANOVA, Tukey tests, and independent‐sample t‐test.

Results

Extended acid‐etching times notably increased ΔE2000 values for enamel, surpassing acceptable thresholds in all groups except for the 5‐s acid‐etching followed by adhesive application. Dentin ΔE2000 remained stable regardless of surface treatment. Machine learning highlighted the influence of acid etching and surface roughness on enamel. Bur tape color had minimal impact.

Conclusions

The effects of acid etching on the color vary between enamel and dentin. Greater attention should be focused on enamel surface. Acid‐etching time should be appropriately reduced.

Clinical Significance

Comprehending the varying impacts of surface treatment on the color of enamel and dentin could contribute to achieving superior esthetic outcomes.
Enhanced Tolerability and Improved Outcomes in Acne Management: A Real‐World Study of Dermocosmetic Adjunctive Therapy
Authors: Suh Dong Hye , Kim Tae‐Eun , Lee Sang Jun , Jeong Su Jin , Baek Eunsun , Shin Min Kyung
Published: January 2025

Background

Topical retinoids, while renowned for their efficacy in treating acne vulgaris, are often hampered by inter‐individual variability in tolerability. This challenge, primarily driven by side effects like erythema, scaling, and dryness, significantly impacts patient adherence and, ultimately, treatment outcomes.

Aims

This prospective, multi‐center, observational study investigated the novel role of a specific dermocosmetic regimen as adjunctive therapy, focusing on its ability to mitigate retinoid‐induced side effects and enhance the overall tolerability of acne treatment regimens in a Korean population.

Patients and Methods

We enrolled 304 patients receiving conventional acne therapies and integrated a standardized dermocosmetic regimen (foaming facial wash and moisturizer) for 12 weeks. Our primary endpoint assessed changes in skin sensitivity scores in both retinoid and non‐retinoid users. We incorporated a patient‐reported outcome measure evaluating acne's impact on quality of life across different facial areas as a secondary endpoint.

Results

Our results revealed a significant improvement in skin sensitivity across both patient groups, effectively mitigating the anticipated heightened sensitivity in retinoid users. This finding suggests that dermocosmetics may hold the key to unlocking consistent, age‐independent tolerance to retinoid therapy. Furthermore, we observed a compelling correlation between improvements in cheek acne and enhanced quality of life, highlighting the profound psychological impact of this specific facial area.

Conclusions

This study pioneers a new understanding of holistic acne management, emphasizing the synergistic potential of dermocosmetics in enhancing treatment adherence, improving long‐term outcomes, and ultimately transforming patients' lives.
Genomics‐Driven Monitoring of Fraxinus latifolia (Oregon Ash) to Inform Conservation and EAB‐Resistance Breeding
Authors: Melton Anthony E. , Faske Trevor M. , Sniezko Richard A. , Thibault Tim , Williams Wyatt , Parchman Thomas , Hamilton Jill A.
Published: January 2025

Understanding the evolutionary processes underlying range‐wide genomic variation is critical to designing effective conservation and restoration strategies. Evaluating the influence of connectivity, demographic change and environmental adaptation for threatened species can be invaluable to proactive conservation of evolutionary potential. In this study, we assessed genomic variation across the range of Fraxinus latifolia, a foundational riparian tree native to western North America recently exposed to the invasive emerald ash borer (Agrilus planipennis; EAB). Over 1000 individuals from 61 populations were sequenced using reduced representation (ddRAD‐seq) across the species' range. Strong population structure was evident along a latitudinal gradient, with population connectivity largely maintained along central valley river systems, and a centre of genetic diversity coinciding with major river systems central to the species' range. Despite evidence of connectivity, estimates of nucleotide diversity and effective population size were low across all populations, suggesting the patchy distribution of F. latifolia populations may impact its long‐term evolutionary potential. Range‐wide estimates of genomic offset, which indicate genomic change required to adjust to future climate projections, were greatest in the eastern and lowest in the southern portions of the species' range, suggesting the regional distribution of genomic variation may impact evolutionary potential longer‐term. To preserve evolutionary capacity across populations needed for the development of breeding and restoration programmes, prioritising conservation of range‐wide genomic diversity will provide a foundation for long‐term species management.
Fear, survival and war on paths to nationhood in Scandinavia, 1809–1914
Authors: Ottosen Morten Nordhagen
Published: January 2025

This article discusses how notions of fear, survival and war influenced nationalism in Scandinavia in the 19th century. It argues that fear of annihilation and concerns about security led to an obsession with size and capability among several leading politicians and national ideologues, making them embrace unification nationalism as a means of national security and survival. Thus, in offering empirical support for Eric Hobsbawm's theory of a threshold principle nations in the 19th century, the article also lends support to John Hutchinson's emphasis on the significance of warfare in nation‐formation. The present article shows that 19th‐century nationalism in Scandinavia in the nineteenth century had a less benign side than traditional studies suggest, as the quest for security and survival in an anarchic and dangerous world meant that war was reckoned with or even thought of as necessary. Consequently, influential contemporaries advocated other kinds of state‐formation than the current Scandinavian nation‐states, deeming unification as the best way to offer security. Yet, notions of fear, survival and war did not only apply to unification nationalism as the case of Norwegian secession nationalism shows. This suggests that, generally, 19th‐century nationalism in Scandinavia is compatible with the realist school of international relations.
Changes in the Pannexin Channel in Ileum Myenteric Plexus and Intestinal Motility Following Ischemia and Reperfusion
Authors: Pereira Thaira Thalita Alves , Mendes Cristina Eusébio , Souza Roberta Figueiroa , Caetano Marcos Antônio Ferreira , Magalhães Henrique Inhauser Riceti , de Paulo Caroline Bures , Watanabe Ii Sei , Castelucci Patricia
Published: January 2025

Background

Intestinal ischemia affects the functioning of the Enteric Nervous System (ENS). Pannexin‐1 channel participates in cell communication and extracellular signaling. Probenecid (PB) is a pannexin‐1 channel inhibitor, which can be a potential treatment for intestinal ischemia.

Aim

Study the effects of ileal ischemia and reperfusion (I/R) and PB treatment on myenteric neurons and in rats.

Methods

Male Wistar rats were used for I/R induction, the ileal vessels were occluded for 45 min and reperfusion was performed after this time. The Sham groups underwent all surgical procedures without obstruction of the ileal vessels. Animals were euthanized 24 h or 14d post‐I/R. The PB group received an injection of PB post‐I/R. Ileal segments were collected for immunofluorescence analyses to identify neurons calretinin immunoreactive (−ir) and pannexin‐1‐ir. Neuronal density (cells/field), area (μm2), intestinal motility, and ultrastructural analyses were performed.

Key Results

The pannexin‐1 channel was double‐labeled with calretinin‐ir neurons. Neuronal density reduced by 21% reduction in calretinin‐ir neurons in the I/R 24 h group and recovered 26% in the PB 24 h group. In the 14d group, there was a 23% reduction in calretinin‐ir neurons in the I/R 14d group and a recovery of 26% in the PB 14d group. The analysis of the contraction after electrical simulation was lower in the I/R 14 d group and recovered in the PB 14d.

Conclusions and Inferences

Intestinal I/R affects myenteric neurons and causes morphological and functional changes. PB was able to attenuate the effects of I/R and could constitute a therapeutic tool for intestinal I/R.
Zoledronic Acid Regulates Osteoclasts via miR‐483‐5p in the BRONJ
Authors: Guo Zhiyong , Yang Jiajin , Li Chunjie , Tang Xiufa , Liu Jiyuan
Published: January 2025

Objectives

Bisphosphonate‐related osteonecrosis of the jaw (BRONJ) is a severe complication of bisphosphonate therapy, with unclear mechanisms. This study investigates the regulatory impact of zoledronic acid (ZOL) on osteoclasts and microRNA (miRNA) expression.

Materials and Methods

Raw264.7 cells and bone marrow‐derived macrophages (BMMs) were used to assess ZOL's effects on proliferation and apoptosis. miRNA array analysis was performed during osteoclastogenesis with ZOL treatment. The role of miR‐483‐5p was examined using miR‐mimics and miR‐inhibitors. A rat BRONJ model was established for in vivo validation.

Results

A concentration of 2 μM ZOL, which did not affect cell proliferation or apoptosis, was used in subsequent experiments. ZOL altered the expression of 64 miRNAs (39 upregulated, 25 downregulated). miR‐483‐5p mimics alleviated ZOL‐induced inhibition of osteoclastogenesis, actin ring formation, bone resorption, and differentiation marker expression, whereas inhibitors enhanced these effects. In vivo, Ago‐miR‐483‐5p promoted wound healing in the BRONJ model, while Antago‐miR‐483‐5p impaired it.

Conclusions

ZOL modulates osteoclast function in BRONJ through miR‐483‐5p inhibition. miR‐483‐5p may serve as a novel therapeutic target for BRONJ treatment, providing new insights into managing this complication.