bluuebunny/crossref_metadata_2025 huggingface dataset:
Life expectancy and geographic variation in mortality: an observational comparison study of six high-income Anglophone countries
Authors: Wilkie Rachel Z , Ho Jessica Y
Published: August 2024

Objective

To compare life expectancy levels and within-country geographic variation in life expectancy across six high-income Anglophone countries between 1990 and 2018.

Design

Demographic analysis using aggregated mortality data.

Setting

Six high-income Anglophone countries (USA, UK, Canada, Australia, Ireland and New Zealand), by sex, including an analysis of subnational geographic inequality in mortality within each country.

Population

Data come from the Human Mortality Database, the WHO Mortality Database and the vital statistics agencies of six high-income Anglophone countries.

Main outcome measures

Life expectancy at birth and age 65; age and cause of death contributions to life expectancy differences between countries; index of dissimilarity for within-country geographic variation in mortality.

Results

Among six high-income Anglophone countries, Australia is the clear best performer in life expectancy at birth, leading its peer countries by 1.26–3.95 years for women and by 0.97–4.88 years for men in 2018. While Australians experience lower mortality across the age range, most of their life expectancy advantage accrues between ages 45 and 84. Australia performs particularly well in terms of mortality from external causes (including drug- and alcohol-related deaths), screenable/treatable cancers, cardiovascular disease and influenza/pneumonia and other respiratory diseases compared with other countries. Considering life expectancy differences across geographic regions within each country, Australia tends to experience the lowest levels of inequality, while Ireland, New Zealand and the USA tend to experience the highest levels.

Conclusions

Australia has achieved the highest life expectancy among Anglophone countries and tends to rank well in international comparisons of life expectancy overall. It serves as a potential model for lower-performing countries to follow to reduce premature mortality and inequalities in life expectancy.
Analysis of the current usage of resuscitative endovascular balloon occlusion of the aorta (REBOA) in pediatric trauma patients: a retrospective observational study from the American College of Surgeons–Trauma Quality Improvement Program databases
Authors: Kuo Ling-Wei , Liao Chien-Hung , Cheng Chi-Tung , Fu Chih-Yuan , Liao Chien-An , Wang Chia-Cheng , Huang Jen-Fu , Hsu Chi-Po
Published: August 2024

Background

Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been an established life-saving procedure for adult trauma patients, but the evidence for its use in pediatric patients is still under question. The purpose of this study was to examine the outcome of REBOA in pediatric patients.

Methods

We retrospectively analyzed observational cohort data from the American College of Surgeons–Trauma Quality Improvement Program from 2017 to 2019. We analyzed 183 506 trauma patients aged 7–18, and 111 patients were matched by propensity score analysis. Basic demographics, injury severity, trauma type, and clinical outcomes of the patients receiving REBOA and those not receiving REBOA were compared. In the REBOA patients, a subgroup analysis was performed to evaluate the potential influence of age and body weight on the outcomes of REBOA.

Results

After the pretreatment factors were balanced for the REBOA and no-REBOA groups, the patients in the REBOA group had more transfused packed red blood cells within the first 4 hours (3250 mL vs. 600 mL, p<0.001), and the mortality rate was higher in the REBOA group, but it did not reach statistical significance (56.8% vs. 36.5%, p=0.067). No significant difference was detected regarding in-hospital complications. In the subgroup analysis of the patients who received REBOA, we discovered no significant difference in mortality and complications between the subgroups when compared by age (>15 years old/≤15 years old) or weight (>58 kg or ≤58 kg).

Conclusions

Pediatric trauma patients who received REBOA were not significantly associated with an increased risk of mortality when compared with no-REBOA patients with matched basic demographics and pretreatment factors. Younger age and lighter body weight did not seem to influence the outcomes of REBOA regarding survival and complications.

Level of evidence

Level III
Deterioration of a compacted soil due to suction loss and desiccation cracking
Authors: Kumar Ashutosh , Azizi Arash , Toll David G.
Published: August 2024

This paper presents the results of laboratory testing of a clayey soil taken from a road subgrade in Tanzania. The results revealed a reduction in the soil water retention capacity, accompanied by shifts in the water retention curves with successive cycles. These changes affected the soil response to shear loading, resulting in decreased shear strength and stiffness with hydraulic cycles. While the soil experienced suction losses due to desiccation cracks and hysteresis effects, these suction variations alone could not account for the observed changes in shear strength, implying that the development of desiccation cracks contributed to reduced strength and stiffness. The results showed that the degradation effect of crack development on the shear strength and elastic modulus of the soil during hydraulic cycles could be justified using a macroscopic degree of saturation, i.e., the degree of saturation of large pores external to the aggregates, through a microstructural-based effective stress approach. This allowed the increase in the large pores resulting from crack development to be accounted for and hence the successive reductions in shear strength and stiffness with drying-wetting cycles. These deterioration effects need to be considered for design of geotechnical infrastructure to ensure stability and resilience of infrastructure over time.
Assessing the importance of detailed forest inventory information using stochastic programming
Authors: Nahorna Olha , Noordermeer Lennart , Gobakken Terje , Eyvindson Kyle
Published: August 2024

Errors in forest inventory data can lead to sub-optimal management decisions and dramatic economic losses. Forest inventory approaches are typically evaluated by their levels of precision and accuracy; however, this overlooks the specific usefulness of the data in decision-making. By evaluating the value of information (VoI), we can assess the usefulness of the data for specific decision-making problems. We evaluated the VoI through stochastic programming for four airborne laser scanning-based inventory approaches. The stochastic programming model explored the trade-off between the maximal net present value and the minimal conditional value at risk of meeting specified periodic income targets. We evaluated a range of periodic targets and risk aversion preference levels. To compare the performance of the inventory approaches, we used a reference dataset that was acquired using a forest harvester with precise positioning. For a wide range of the trade-offs, inventory approaches with higher-quality information provided the best overall performance. If only one of the extreme objectives was desired, less precise inventory approaches were sufficient to produce high-quality solutions.
Probability distributions of atomic scattering lengths
Authors: Bohn John L. , Wang Reuben R.W.
Published: August 2024

The probability distributions of the real and imaginary parts of atomic scattering lengths a are derived, in a two-channel model that allows for inelastic scattering to occur. While the real part of a remains Cauchy-distributed, as predicted for single channel scattering in the classic work of Gribakin and Flambaum, the imaginary part of a is seen to be strongly peaked near zero. Two-body inelastic scattering rates may therefore be smaller in general than a naive estimate would suggest.
Why and how did the COVID pandemic end abruptly?
Authors: Moret Marcelo A. , Phillips James C.
Published: August 2024

Phase transition theory, implemented quantitatively by thermodynamic scaling, has explained the evolution of Coronavirus’ extremely high contagiousness caused by a few key mutations from CoV2003 to CoV2019 identified among hundreds, as well as the later 2021 evolution to Omicron caused by 30 mutations. It also showed that the 2022 strain BA.5 with five mutations began a new path. Here we show that the early 2023 strains BKK with one stiffening mutation confirm that path, and the single flexing mutation of a later 2023 variant EG.5 strengthens it further. The few mutations of the new path have greatly reduced pandemic deaths, for mechanical reasons proposed here.

Graphical abstract
Geological factors in the sustainable management of mine water heating, cooling and thermal storage resources in the UK
Authors: Monaghan Alison A. , Adams Charlotte A. , Bell Rachel A. , Lewis Melinda A. , Boon David , González Quirós Andres , Starcher Vanessa , Farr Gareth , Wyatt Lee M. , Todd Fiona , Walker-Verkuil Kyle , MacAllister Donald John , Abesser Corinna , Palumbo-Roe Barbara , Scheidegger Johanna
Published: August 2024

Re-use of the UK's coal mine water heating, cooling and thermal storage resource is increasing in scale and the number of schemes. The upward trajectory requires 3D planning, regulation and licensing to manage sustainable deployment. We review geological factors controlling thermal and flow processes in the anthropogenically-altered subsurface, critical for resource management with multiple users of the same space. Potential interactions of mine water geothermal schemes with the wider environment are also summarized, leading towards concepts of 3D mine water thermal blocks, protection zones, or management strategies integrating heating, cooling and storage demands.

Factors such as the magnitude, extent and timescale of thermal processes to underpin management approaches are poorly quantified by data measured at-scale under varying pumping rates and thermal loads. We demonstrate early insights of how two infrastructures, the UK Geoenergy Observatory in Glasgow and the Coal Authority's Mine Water Heat Living Lab in Gateshead, can measure and monitor heat-flow processes in real world settings to provide an evidence base. For example, a thermal storage test at Glasgow showed rapid temperature changes in the rock and mine workings at the re-injection borehole and indicated an influence of lithologically-controlled transmissivity and thermal conductivity on temperature dissipation and recovery.
Public Business and Private Accounts
Authors: Grimmelmann James
Published: August 2024

Dek:

Government officials cannot block critics on social media.
An Exploration of IFLA LRM for Literature Data Representation
Authors: Gagnon Michel , Font Ludovic , Zouaq Amal
Published: August 2024

The digital humanities have witnessed a clear development in recent years due partly to their adoption of Semantic Web and linked data technologies and the creation of knowledge bases. In this work, we target the creation of an ontology and knowledge base for literature data representation based on the IFLA Library Reference Model (LRM). IFLA LRM is the main model for book-related data, allowing for a fine representation of the various layers that constitute a book. However, by design, it doesn’t deal with some aspects usually available in literature databases, such as information about authors, literary awards or book themes. As a result, LRM requires some extensions to be able to represent ancillary data. Another challenge is the querying of IFLA LRM knowledge bases, with a performance cost that comes with the fine-grained expressivity of the LRM model, which creates longer and therefore typically slower SPARQL queries. In this work, we propose an extension to the IFLA LRM ontology called IFLA LRM* that targets these limitations including a connection to the vocabulary Schema.org and to the taxonomies Thema and Dewey Decimal, and the representation of literary awards. We also present a practical case study on using our extended model to create a Quebec literature knowledge base, discussing the interest of our extensions.
Recruiting Practices in Informal CS Learning
Authors: Perdriau Christopher , Solomon Meron , Ko Amy
Published: August 2024

Introduction: Computer science (CS) lacks representation from people who identify as one or more of the following identities: woman, Black, Indigenous, Hispanic, Latina/Latino/Latinx, or disabled. We refer to these groups as historically underrepresented groups (HUGs). Informal learning, like CS summer camps and hackathons, can increase interest in K-12 students but still struggles to broaden participation. Objectives: In this study, we examine one source of struggle for informal learning programs: recruiting practices. Methods: Toward the goal of understanding this struggle, we interviewed 14 informal K-12 CS learning programs across a diverse region in the Northwestern United States to understand what recruiting practices are being used. We used a cultural competency lens to examine the variation within recruiting practices and how some practices could lead to broader participation in computing. Results: We identified 18 different recruiting practices used by informal CS learning program organizers. Some programs had similar practices, but subtle differences in implementation that led them to fall at different points on the cultural competence continuum. More culturally competent implementations generally involve reflection on the needs of specific populations that programs were trying to recruit, on why previous recruiting implementations did not work, and on feedback from stakeholders to change their implementations. This is the first article to investigate how the implementation of the recruiting practice determines its cultural competency. Conclusion: Results from this study illuminate some of the problems informal CS programs face in broadening participation in computing and provide insights on how program organizers’ can overcome them. Our work highlights how students or parents access resources, the challenges program organizers encounter, and whether current recruiting practices effectively engage students from HUGs.
A Meta-Learning Approach to Mitigating the Estimation Bias of Q-Learning
Authors: Tan Tao , Xie Hong , Shi Xiaoyu , Shang Mingsheng
Published: August 2024

It is a longstanding problem that Q-learning suffers from the overestimation bias. This issue originates from the fact that Q-learning uses the expectation of maximum Q-value to approximate the maximum expected Q-value. A number of algorithms, such as Double Q-learning, were proposed to address this problem by reducing the estimation of maximum Q-value, but this may lead to an underestimation bias. Note that this underestimation bias may have a larger performance penalty than the overestimation bias. Different from previous algorithms, this article studies this issue from a fresh perspective, i.e., meta-learning view, which leads to our Meta-Debias Q-learning. The main idea is to extract the maximum expected Q-value with meta-learning over multiple tasks to remove the estimation bias of maximum Q-value and help the agent choose the optimal action more accurately. However, there are two challenges:
(1) How to automatically select suitable training tasks? (2) How to positively transfer the meta-knowledge from selected tasks to remove the estimation bias of maximum Q-value?
To address the two challenges mentioned above, we quantify the similarity between the training tasks and the test task. This similarity enables us to select appropriate “partial” training tasks and helps the agent extract the maximum expected Q-value to remove the estimation bias. Extensive experiment results show that our Meta-Debias Q-learning outperforms SOTA baselines drastically in three evaluation indicators, i.e., maximum Q-value, policy, and reward. More specifically, our Meta-Debias Q-learning only underestimates

\(1.2*10^{-3}\)

than the maximum expected Q-value in the multi-armed bandit environment and only differs

\(5.04\%-5\%=0.04\%\)

than the optimal policy in the two states MDP environment. In addition, we compare the uniform weight and our similarity weight. Experiment results reveal fundamental insights into why our proposed algorithm outperforms in the maximum Q-value, policy, and reward.
Considering Socially Scalable Human-Robot Interfaces
Authors: Benjamin Victor
Published: August 2024

Collaborative robots are becoming increasingly present in everyday life, with applications ranging food and parcel delivery, security, and more. They can offer great value propositions for organizations and consumers. However, most people lack knowledge of how to interact with robots, and many robots themselves necessitate formal training that can be inaccessible to many and thus not societally scalable. Further, there is a lack of existing work investigating interfaces designs that can support non-dyadic interactions consisting of two or more individuals interacting with a robot sequentially and simultaneously; such interactions will be common in real-world usage. This research explores the efficacy of natural language interfaces for human–robot interaction through a human experiment and post-experiment survey. Results show that the natural language interface can afford teams enhanced capabilities to share robot control and avoid errors relative to other interfaces, while also increasing user perceptions towards overall interaction.
Perineuronal nets’ role in metabolism
Authors: Zhang Nan , Song Beite , Bai Peng , Du Li , Chen Lulu , Xu Yong , Zeng Tianshu
Published: August 2024

Perineuronal nets (PNNs), specialized extracellular matrix (ECM) structures that envelop neurons, have recently been recognized as key players in the regulation of metabolism. This review explores the growing body of knowledge concerning PNNs and their role in metabolic control, drawing insights from recent research and relevant studies. The pivotal role of PNNs in the context of energy balance and whole body blood glucose is examined. This review also highlights novel findings, including the effects of astroglia, microglia, sex and gonadal hormones, nutritional regulation, circadian rhythms, and age on PNNs dynamics. These findings illuminate the complex and multifaceted role of PNNs in metabolic health.
Recognizing Critical Stations in Urban Rail Transit Networks Based on the PCA‐TPE Method: Shanghai Metro as an Example
Authors: Xu Xueguo , Xu Chen
Published: August 2024

The identification of core stations in urban rail transit (URT) networks remains a vital issue in network structure organization analysis and an integral part of network reliability evaluation. However, the identification of critical stations with a single centrality metric has limitations and the varying interactions between stations cannot be ignored. In this paper, a novel integrated approach is proposed by using the principal component analysis and topological potential considering entropy (PCA‐TPE) method. Taking the Shanghai metro (SHM) network as a case study, a Space L network model is constructed and the network topology characteristics are analyzed. Moreover, the susceptible‐infected (SI) model and the network failure simulation are employed to demonstrate the effectiveness of the proposed method. The results show that the SHM network exhibits characteristics of both small‐world networks and scale‐free networks. According to the experiments of the SI model, the nodes obtained by the PCA‐TPE method have stronger spreading influence than those derived by other methods, especially in the initial stage. The failure simulations illustrate that attacks against the nodes detected by the PCA‐TPE method will lead to devastating network failures. Hence, the proposed method is effective for identifying critical nodes in URT networks, and the findings of the research can provide theoretical evidence for the development planning and emergency management of the public traffic system.
Cellulose Nanofibers/Reduced Graphene Oxide Nanocomposites for Humidity Sensor
Authors: Rashid Adib Bin , Kafy Abdullahil , Kabir Nahiyan , Ishrak Hasin , Rifat Fahim Ferdin
Published: August 2024

Cellulose nanofibers (CNFs) are part of organic crystallization macromolecular compounds that can be found in bacteria’s capsular polysaccharides and plant fibers. CNFs have a lot of potential as suitable matrices and advanced materials, and there have been a lot of studies done on them so far, both in terms of modifying them and inventing uses for them. In this paper, CNFs/reduced graphene oxide (GO) (rGO) nanocomposites were developed to create renewable, flexible, and cheap humidity sensors. The composite film’s performance as a humidity sensor was evaluated by analyzing the variations in capacitance at different humidity levels. The synthesized composite film underwent characterization using various analytical techniques, including scanning electron microscopy (SEM), UV (ultraviolet)/Vis (visible) spectrophotometry, Fourier transform infrared spectroscopy (FTIR), and thermomechanical analysis (TMA). The sensing mechanism is elucidated based on hydrophilic functional groups within the composite material. It has been observed that 3 wt% rGO/CNF composite is the best suited for humidity sensing among all other samples.
ResNet Deep Learning‐Based Inversion Method for Sea Surface Wind Field
Authors: Li Ziwei , Guo Jianzhong , Zhang Baowei
Published: August 2024

This paper presents a method to invert the sea surface wind field from Sentinel‐1 synthetic aperture radar (SAR) interferometric wide swath (IW) band mode ground range detected (GRD) vertical polarization (VV) data based on the deep residual network (ResNet). Compared with the traditional algorithm (i.e., using geophysical model functions (GMFs)), the wind field inversion based on the ResNet deep learning method solves the problem of separate wind direction and wind speed inversion. The ResNet model is developed based on the results of 212 VV polarized IW images and cross calibrated multiplatform (CCMP) data collected in 2021 in the offshore waters of China. The root mean square error, standard deviation, and bias of the inverse wind direction of the ResNet model are 12.5°, 9.8°, and 7.4°, respectively, and the root mean square error, standard deviation, and bias of the inverse wind speed are 2.33, 1.495, and −1.375. The ResNet is better than the conventional local gradient and C‐band model models, further confirming the advantages shown by the deep learning algorithm in nonlinear fitting and its potential application in sea surface wind field inversion.
Assessing the Efficacy and Safety of Intradermal Injection of Different Doses of Botulinum Toxin Type A: A Randomized, Double‐Blind, Placebo‐Controlled, Split‐Face Pilot Study in Rosacea Patients with Erythematic Telangiectasia
Authors: Jiang Yuan , Wang Fengyuan , Chen Wenqi , Chen Yihe , Dai Jie
Published: August 2024

Introduction. Rosacea is a common chronic inflammatory skin disease of the central facial skin with unknown origin, significantly impacting quality of patient’s life and causing various psychosocial problems. Erythematotelangiectatic rosacea (ETR) is characterized by paroxysmal flushing that occurs repeatedly and is easily resistant to therapeutic drugs. While microinjection of type A botulinum toxin (BTX) can treat ETR, there is no consensus on the injection dose, and strong evidence to verify its efficacy and safety is lacking. This randomized, double‐blind, split‐face clinical study aimed to investigate the efficacy, safety, and optimal dose of two different single‐point injection doses (0.5 U and 1 U) of BTX in the treatment of rosacea. Methods. Twenty‐six patients with ETR were randomly assigned to receive different single‐point injections of BTX (0.5 U and 1 U, respectively) every 1 cm on one half of the face. The Clinical Erythema Score (CEA), VISIA red area absolute value, Global Aesthetic Improvement Scale Score (GAIS), and recurrence at 12‐week follow‐up were evaluated at baseline, 2,4, 8, and 12 weeks after injection. Additionally, the Dermatological Quality of Life Index (DLQI) questionnaire survey and adverse reactions were also recorded. Results. All twenty‐six patients completed the follow‐up visits and were included in the analysis. Compared to the 0.5 UBTX‐treated side, the CEA score showed significantly improvement in erythema and flushing at 2, 4, and 8 weeks after injection on the 1 U BTX‐treated side (P < 0.05). The mean absolute value of the red area of VISIA was ‐19.12 ± 51.91 on 1 U BTX‐treated side and 2.5 ± 42.08, on 0.5 UBTX‐treated side at 4 weeks after treatment, showing significant improvement on the 1 U side (P < 0.05). GAIS and DLQI were also significantly improved from Week 4 to Week 12 and Week 2 to Week 12, respectively (P < 0.05). There was no recurrence of symptoms with either 0.5 U or 1 U injection by 12 weeks. Apart from one patient who experienced facial tightness and three patients who had temporary aggravation of erythema, all of which resolved without treatment, 22 patients did not report any side effects except for injection pain during the procedure. Conclusions. BTX‐A can significantly improves symptoms and quality of life in patients with refractory rosacea with few side effects. A single‐point injection of 1 U was more effective. This trial is registered with NCT06282679.
Heat Transfer Analysis Methodology for Compression Hydrogen Storage Tank during Charge–Discharge Cycle
Authors: Luo Hao , Yuan Chengqing , Wang Li , Yang Tianqi , Tong Liang , Ye Feng , Yuan Yupeng , Bénard Pierre , Chahine Richard , Xiao Jinsheng
Published: August 2024

Heat transfer analysis for the compression hydrogen storage tank (CHST) during the charge–discharge cycle is necessary to ensure quick and safe refueling for fuel cell vehicles. In this paper, a dual‐zone dual‐temperature (DZDT) model for a CHST during the charge–discharge cycle process is established. The constant/variable mass flow rates and heat transfer coefficients (HTCs) are combined to form three methods. Method 1 uses constant mass flow rate and constant HTC. Method 2 uses variable mass flow rate and variable HTC calculated through the energy conservation equation. Method 3 uses variable mass flow rate and variable HTC calculated through the empirical equation. Then, these methods are applied to the DZDT model for heat transfer analysis in three cases. Research shows that for the charging process, the simulated hydrogen temperatures by Method 2 agree well with experiment data for three CHSTs. Method 1 has a maximum error of about 20°C for 19 L CHST, 15°C for 29 L CHST, and 25°C for 40 L CHST. The error of Method 3 is between Methods 1 and 2. The simulated hydrogen pressures by Methods 2 and 3 agree well with the experimental data, while Method 1 has a maximum error of about 5 MPa for 19 L CHST, 10 MPa for 29 L CHST, and 3 MPa for 40 L CHST. For the discharge process, the simulated hydrogen temperatures by Methods 2 and 3 have a relatively slight difference with the experimental data, while Method 1 has relatively significant differences for three CHSTs. Only slight differences exist between the simulated hydrogen pressures by Methods 1, 2, and 3 with the experimental data for three CHSTs. In short, Method 2 can simulate the hydrogen temperature and pressure well during the charge–discharge process. Method 3 can simulate the approximate hydrogen temperature and precise hydrogen pressure during the charge–discharge process. Method 1 can only simulate the hydrogen pressure during the discharging process. The conclusions of this article can inform researchers which analysis methods are more reasonable to choose in future hydrogen‐filling studies.
Increased Risk of Cutaneous T‐Cell Lymphoma Development after Dupilumab Use for Atopic Dermatitis
Authors: Mandel Jenna , Mehta Jaanvi , Hafer Ramsay , Ayub Mahaa , Nusrat Faria , Yang Henry , Porcu Pierluigi , Nikbakht Neda
Published: August 2024

There have been several reports of dupilumab use and the development of CTCL; however, the risk of CTCL development has not been adequately evaluated at the population level. The objective of this study is to determine whether dupilumab administration for AD is associated with an increased risk of developing CTCL and to identify at‐risk populations within this group. This retrospective cohort study used TriNetX, a deidentified medical record database including over 107 million patients, to identify eligible patients. Treatment and control groups were evaluated for the development of CTCL. Patients of any age with a documented diagnosis of AD were included. The treatment cohort included individuals treated with dupilumab, while the control cohort included AD patients treated with alternative therapies. Selected biologics were excluded from both groups. Subgroup analyses were performed to evaluate three age groups and to identify whether the risk of CTCL development was higher within a given time frame after starting dupilumab. We identified a total of 1,181,533 patients with AD. Of these, 19,612 patients were prescribed dupilumab. Both treatment and control groups included 19,612 patients matched for age, race, and sex. The mean age was 32.3 years (P = 0.96), and females accounted for approximately 52% (P = 0.93) in both groups. Patients treated with dupilumab for AD had an increased relative risk (RR) of developing CTCL compared to those never treated with dupilumab (RR = 4.59, 95% confidence interval 2.459–8.567, P < 0.0001). Subgroup analysis revealed that about half of the CTCL cases after dupilumab therapy (54.5%, 30/55) occurred in patients over the age of 60 years. In contrast, all CTCL cases (100%, 12/12) within the untreated cohort were observed in individuals over the age of 60. Of the patients diagnosed with CTCL following dupilumab use, the majority (62%, 34/55) were diagnosed within the first year. Overall, we find that the use of dupilumab for treating AD is associated with an increased relative risk of developing CTCL. This risk is highest in the first year of therapy and in adult patients. These findings suggest exercising caution in treating select groups of patients with dupilumab.
Is It Time to Resist Using RECIST as a Primary Endpoint for Rare Tumor Trials?
Authors: Van Tine Brian A. , Haarberg Sasha
Published: August 2024

Epithelioid hemangioendothelioma is an ultra-rare cancer driven by YAP–CAMTA1 fusion. Based on the link of the fusion to the MEK pathway, SARC33 was performed. It is a phase 2 trial examining trametinib that missed its primary objective by RECIST but demonstrated patient-reported outcome benefits in improved pain.

See related article by Schuetze et al., p. 4584
Figure 3 from A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors
Authors: Vernet Rémi , Fernandez Eugenio , Migliorini Denis , Ancrenaz Virginie , Charrier Emily , Belkouch Marie-Claude , Von Rohr Olivier , Urwyler Muriel , De Vito Claudio , Renaux Jessica , Villard Jean , Rubin Olivier , Grogg Julien , Mach Nicolas
Published: August 2024

Antitumor activity of MVX-ONCO-1. A, Waterfall plot of the maximum percentage of tumor size change in each patient. B, Percentage changes from baseline of tumor size (sum of longitudinal change of recorded lesions) over time in each patient.
Data from Clinical Efficacy of the HIV Protease Inhibitor Indinavir in Combination with Chemotherapy for Advanced Classic Kaposi Sarcoma Treatment: A Single-Arm, Phase II Trial in the Elderly
Authors: Sgadari Cecilia , Scoppio Biancamaria , Picconi Orietta , Tripiciano Antonella , Gaiani Francesca Maria , Francavilla Vittorio , Arancio Angela , Campagna Massimo , Palladino Clelia , Moretti Sonia , Monini Paolo , Brambilla Lucia , Ensoli Barbara
Published: August 2024

Abstract
Kaposi sarcoma is a rare angioproliferative disease associated with human herpes virus-8 (HHV-8) infection. Kaposi sarcoma is frequent and aggressive in HIV-infected people, whereas the classic form (CKS) generally has an indolent course. Notably, all conventional therapies against Kaposi sarcoma have only temporary efficacy. We have previously shown that indinavir, a HIV protease-inhibitor with direct antiangiogenic and antitumor activity, is safe and effective in patients with early CKS, whereas effects are less prominent in advanced disease, probably due to the larger tumor mass. Therefore, the clinical response to indinavir was assessed in patients with advanced CKS after debulking chemotherapy. This was a monocentric phase 2 trial in elderly with progressive/advanced CKS treated with debulking chemotherapy and indinavir combined, followed by a maintenance phase with indinavir alone. Secondary endpoints included safety and Kaposi sarcoma biomarker evaluation.

All evaluable patients (22) responded to debulking therapy. Out of these, 16 entered the indinavir maintenance phase. The overall response rate at end of maintenance was 75% (estimated median response-duration 43 months). Moreover, most responders showed further clinical improvements (lesion number/nodularity) during maintenance and post-treatment follow-up. Notably, after relapse, progressors did not require systemic Kaposi sarcoma therapy and showed clinical improvements (including disease stabilization) remaining on study. Responders also showed immune status amelioration with a consistent B-cell increase and positive changes of other biomarkers, including anti-HHV-8 natural killer activity. In advanced CKS a strategy combining indinavir and chemotherapy is safe and associated with high and durable response rates and it could be rapidly adopted for the clinical management of these patients.
Significance:
This phase-2 trial showed that the HIV protease inhibitor indinavir may boost and extend the duration of the effects of chemotherapy in elderly with advanced progressive classic Kaposi sarcoma, without additional toxicity. Further, the amelioration of the immune status seen in responders suggests a better control of HHV-8 infection and tumor-cell killing. Thus, indinavir combined with chemotherapy may represent an important tool for the clinical management of classic Kaposi sarcoma in elderly patients.
Phase I Study of Simlukafusp Alfa (FAP-IL2v) with or without Atezolizumab in Japanese Patients with Advanced Solid Tumors
Authors: Koyama Takafumi , Yonemori Kan , Shimizu Toshio , Sato Jun , Kondo Shunsuke , Sudo Kazuki , Yoshida Tatsuya , Katsuya Yuki , Imaizumi Tatsuki , Enomoto Masashi , Seki Ryoko , Yamamoto Noboru
Published: August 2024

Purpose:

The aim of the study was to evaluate the safety/tolerability and pharmacokinetics of simlukafusp alfa (FAP-IL2v), an immunocytokine containing an anti-fibroblast activation protein-α (FAP) antibody and an IL2 variant, administered alone or with the PDL1 inhibitor atezolizumab, in Japanese patients with advanced solid tumors.

Patients and Methods:

In this phase 1, open-label, dose-escalation study, patients received i.v. FAP-IL2v at 10 or 15/20 mg alone or 10 mg when combined with i.v. atezolizumab. The primary objectives were identification of dose-limiting toxicities (DLT), recommended dose, and maximum tolerated dose, and evaluation of the safety/tolerability and pharmacokinetics of FAP-IL2v alone and combined with atezolizumab.

Results:

All 11 patients experienced adverse events (AE) during FAP-IL2v treatment. Although most AEs were of mild severity, four treatment-related AEs led to study treatment discontinuation in two patients: one with infusion-related reaction, hypotension, and capillary leak syndrome, and the other with increased aspartate aminotransferase. No AE-related deaths occurred. One DLT (grade 3 hypotension) occurred in a patient receiving FAP-IL2v 15/20 mg alone. The recommended dose and maximum tolerated dose could not be determined. The pharmacokinetics of FAP-IL2v remained similar with or without atezolizumab. The study was terminated early as FAP-IL2v development was discontinued because of portfolio prioritization (not for efficacy/safety reasons).

Conclusions:

This study describes the safety/tolerability of FAP-IL2v 10 mg alone and in combination with atezolizumab in Japanese patients with advanced solid tumors; one DLT (hypotension) occurred with FAP-IL2v 15/20 mg. However, dose escalation of FAP-IL2v was not conducted because of early study termination.

Significance:

This phase I study assessed the safety/tolerability and PK of simlukafusp alfa alone or combined with atezolizumab in Japanese patients with advanced solid tumors. No notable differences in PK were noted with the combination versus simlukafusp alfa alone; however, high-dose simlukafusp alfa treatment was associated with recombinant IL2-related toxicity, despite the drug's FAP targeting and IL2Rβγ-biased IL2 variant design.
Delivery Room Handling of the Newborn: Filling the Gaps
Authors: Saugstad Ola Didrik , Kapadia Vishal , Vento Maximo
Published: August 2024

Background: Newborn resuscitation algorithms have since the turn of the century been more evidence-based. In this review, we discuss the development of American Heart Association (AHA) and the International Liaison Committee on Resuscitation (ILCOR)’s algorithm for newborn resuscitation from 1992–2024. We have also aimed to identify the remaining gaps in non-evidenced practice. Summary: Of the 22 procedures reviewed in the 2020 ILCOR recommendations, the evidence was either low, very low, or non-existing. The strength of recommendation is weak or non-existing for most topics discussed. Several knowledge gaps are also summarized. The special challenge for low- and middle-income countries (LMIC) is discussed. Key Messages: Newborn resuscitation is still not evidence-based, although great progress has been achieved the recent years. We have identified several knowledge gaps which should be prioritized in future research. The challenge of obtaining evidence-based knowledge from LMIC should be focused on in future research.
Morphological study of the sclerites of the species Renilla muelleri Kölliker, 1872 (Anthozoa, Octocorallia, Pennatulacea)
Authors: Gonella Fátima Micaela , Acuña Fabián Horacio , Garese Agustín
Published: August 2024

Some octocorals (Cnidaria, Anthozoa) can produce a sub-millimeter to a millimeter-range skeleton of calcium carbonate, known as sclerites. Sclerites have diverse morphological characters, such as size, and shape features that give them relevance as taxonomic characters at different levels. Renilla Lamarck, 1816, is a genus of the order Pennatulacea (Octocorallia), in which colonies are characterized by two distinct zones: a peduncle, which anchors them to the substrate, and a rachis that supports the polyps. In the case of Renilla muelleri Kölliker, 1872, prior research established the presence of similar sclerites in both the peduncle and the rachis. Nevertheless, the potential morphological variations of these sclerites among colonies and within different colony regions have yet to be assessed to determine the stability of these characteristics at the species level. This study aimed to describe and compare the external microscopic morphology and biometry of the sclerites of Renilla muelleri, enhancing their identification and assessing their consistency within the species. Sclerite composition was examined across the entire colony, and we analyzed length variation among colonies using generalized linear models (GLM) and within colony zones using generalized linear mixed models (GLMM). Additionally, the external microscopic morphology of all sclerites was examined through scanning electron microscopy (SEM). Based on size, two types of sclerites, namely large and small, were identified within the colonies. Both types exhibited significant size differences among colonies. Furthermore, the large sclerites displayed notable variations between zones, with those in the rachis being the largest and holding the highest rank within the colonies. In terms of external microscopic morphology, the sclerites exhibited considerable variability, making it challenging to establish clear groupings based on these characteristics. Based on the obtained results, it can be concluded that both the biometry and external microscopic morphology of sclerites do not exhibit consistency as characteristics in Renilla muelleri highlighting the ambiguity in defining Renilla species.
Differential distribution of Jatrophobia brasiliensis (Diptera, Cecidomyiidae) on Manihot caerulenses (Euphorbiaceae) in edge and interior environments in a cerrado in Brazil
Authors: Araújo Walter Santos de , Oliveira Bruno Maia , Gonçalves Priscila Santos , Silveira Luana Teixeira , Freitas Érica Vanessa Durães de
Published: August 2024

No presente estudo, testamos se a distribuição de galhas de insetos induzidas por Jatrophobia brasiliensis (Rübsaamen, 1907) (Diptera, Cecidomyiidae) em Manihot caerulenses (Euphorbiaceae) difere entre ambientes de borda e interior em uma savana neotropical no Brasil. Testamos a hipótese de que a abundância de galhas é maior na borda da vegetação, exposta a constante poeira de uma estrada não pavimentada, do que no interior da savana, onde a penetração de poeira é menor. O estudo foi realizado no Parque Estadual da Serra do Cabral, onde foram amostradas 28 plantas, sendo selecionadas 14 no interior da vegetação e 14 na borda da estrada. Foram coletadas um total de 269 galhas de Jatrophobia brasiliensis, sendo 203 galhas em plantas da borda e 66 galhas em plantas do interior. Corroborando nossa expectativa, registramos um maior número de galhas de insetos em plantas da borda em comparação com as plantas do interior. Sugerimos que a poeira é o principal estressor em ambientes de borda de savanas neotropicais, ao contrário de vegetações de floresta, onde as mudanças microclimáticas podem ser mais relevantes. Nossos resultados indicam que as alterações ambientais causadas pela deposição de poeira na borda afetam a distribuição de galhas de insetos em savanas neotropicais.
Restoring Atrial T-Tubules Augments Systolic Ca Upon Recovery From Heart Failure
Authors: Caldwell Jessica L. , Clarke Jessica D. , Smith Charlotte E.R. , Pinali Christian , Quinn Callum J. , Pearman Charles M. , Adomaviciene Aiste , Radcliffe Emma J. , Watkins Amy , Horn Margaux A , Bode Elizabeth F. , Madders George W.P. , Eisner Mark , Eisner David A. , Trafford Andrew W. , Dibb Katharine M.
Published: August 2024

BACKGROUND:

Transverse (t)-tubules drive the rapid and synchronous Ca
2+
rise in cardiac myocytes. The virtual complete atrial t-tubule loss in heart failure (HF) decreases Ca
2+
release. It is unknown if or how atrial t-tubules can be restored and how this affects systolic Ca
2+
.

METHODS:

HF was induced in sheep by rapid ventricular pacing and recovered following termination of rapid pacing. Serial block-face scanning electron microscopy and confocal imaging were used to study t-tubule ultrastructure. Function was assessed using patch clamp, Ca
2+
, and confocal imaging. Candidate proteins involved in atrial t-tubule recovery were identified by western blot and expressed in rat neonatal ventricular myocytes to determine if they altered t-tubule structure.

RESULTS:

Atrial t-tubules were lost in HF but reappeared following recovery from HF. Recovered t-tubules were disordered, adopting distinct morphologies with increased t-tubule length and branching. T-tubule disorder was associated with mitochondrial disorder. Recovered t-tubules were functional, triggering Ca
2+
release in the cell interior. Systolic Ca
2+
,
I
Ca-L
, sarcoplasmic reticulum Ca
2+
content, and sarcoendoplasmic reticulum Ca
2+
ATPase function were restored following recovery from HF. Confocal microscopy showed fragmentation of ryanodine receptor staining and movement away from the z-line in HF, which was reversed following recovery from HF. Acute detubulation, to remove recovered t-tubules, confirmed their key role in restoration of the systolic Ca
2+
transient, the rate of Ca
2+
removal, and the peak L-type Ca
2+
current. The abundance of telethonin and myotubularin decreased during HF and increased during recovery. Transfection with these proteins altered the density and structure of tubules in neonatal myocytes. Myotubularin had a greater effect, increasing tubule length and branching, replicating that seen in the recovery atria.

CONCLUSIONS:

We show that recovery from HF restores atrial t-tubules, and this promotes recovery of
I
Ca-L
, sarcoplasmic reticulum Ca
2+
content, and systolic Ca
2+
. We demonstrate an important role for myotubularin in t-tubule restoration. Our findings reveal a new and viable therapeutic strategy.
Psychosocial Stressors at Work and Atrial Fibrillation Incidence: An 18‐Year Prospective Study
Authors: Tiwa Diffo Edwige , Lavigne‐Robichaud Mathilde , Milot Alain , Brisson Chantal , Gilbert‐Ouimet Mahée , Vézina Michel , Talbot Denis , Trudel Xavier
Published: August 2024

Background

Psychosocial stressors at work, defined by the job strain and effort–reward imbalance at work (ERI) models, were shown to increase coronary heart disease risk. No previous study has examined the adverse effect of psychosocial stressors at work from both models on atrial fibrillation (AF) incidence. The objective of this study was to examine the separate and combined effect of psychosocial stressors at work from the job strain and ERI models on AF incidence in a prospective cohort study.

Methods and Results

A total of 5926 white‐collar workers (3021 women and 2905 men) free of cardiovascular disease at baseline were followed for an average of 18 years. Job strain (high psychological demands combined with low decision latitude) and ERI were assessed using validated instruments. AF events were identified in medical databases with universal coverage. Hazard ratios (HRs) with 95% CIs were estimated using Cox regression models, controlling for socioeconomic characteristics and lifestyle‐related and clinical risk factors. A total of 186 AF incident events were identified over 18 years. Workers exposed to job strain (HR, 1.83 [95% CI, 1.14–2.92]) and ERI (HR, 1.44 [95% CI, 1.05–1.98]) had a higher risk of AF in fully adjusted models. Combined exposure to job strain and ERI was associated with a 2‐fold AF risk increase (HR, 1.97 [95% CI, 1.26–3.07]).

Conclusions

Psychosocial stressors at work from the job strain and ERI models are associated with an increased risk of AF, separately and in combination. Workplace prevention strategies targeting these psychosocial stressors at work may be effective to reduce the burden associated with AF.