bluuebunny/crossref_metadata_2025 huggingface dataset:
Semantically-Informed Graph Neural Networks for Irony Detection in Turkish
Authors: Bölücü Necva , Can Burcu
Published: November 2024

Social media plays an important role in expressing the thoughts and sentiments of users. Irony is a way of stating a sentiment about something by expressing the opposite of the intended literal meaning. Irony detection is a recent emerging task in low-resource languages, although other tasks related to sentiment, such as sentiment analysis and emotion detection, have been widely tackled. In this study, we investigate Graph Neural Networks (GNNs) for irony detection in Turkish, a low-resource language in sentiment-related tasks. We incorporate semantic information into the GNNs using the Universal Conceptual Cognitive Annotation (UCCA) framework. Extensive experimental results and in-depth analysis show that our models outperform state-of-the-art irony detection models in Turkish. Our UCCA-GAT (UCCA-Graph Attention Network) model achieves an F
1
-score of 94.85% (7.362% gain over the state-of-the-art) on the Turkish-Irony-Dataset and an accuracy of 72.82% (4.39% gain over the state-of-the-art) on the IronyTR Dataset. We also provide a comprehensive analysis of the proposed models to understand their limitations.

1
Genetic Approaches for Identifying and Characterizing Effectors in Bacterial Pathogens
Authors: Ellis Nicole A. , Machner Matthias P.
Published: November 2024

Microbial pathogens have coevolved with their hosts, often for millions of years, and in the process have developed a variety of virulence mechanisms to ensure their survival, typically at the host's expense. At the center of this host–pathogen warfare are proteins called effectors that are delivered by bacteria into their host where they alter the intracellular environment to promote bacterial proliferation. Many effectors are believed to have been acquired by the bacteria from their host during evolution, explaining why researchers are keen to understand their function, as this information may provide insight into both microbial virulence strategies and biological processes that happen within our own cells. Help for accomplishing this goal has come from the recent development of increasingly powerful genetic approaches, which are the focus of this review.
A Genetic Bridge Between Medicine and Neurodiversity for Autism
Authors: Leblond Claire S. , Rolland Thomas , Barthome Eli , Mougin Zakaria , Fleury Mathis , Ecker Christine , Bonnot-Briey Stéf , Cliquet Freddy , Tabet Anne-Claude , Maruani Anna , Chaumette Boris , Green Jonathan , Delorme Richard , Bourgeron Thomas
Published: November 2024

Autism represents a large spectrum of diverse individuals with varying underlying genetic architectures and needs. For some individuals, a single de novo or ultrarare genetic variant has a large effect on the intensity of specific dimensions of the phenotype, while, for others, a combination of thousands of variants commonly found in the general population are involved. The variants with large impact are found in up to 30% of autistic individuals presenting with intellectual disability, significant speech delay, motor delay, and/or seizures. The common variants are shared with those found in individuals with attention-deficit/hyperactivity disorder, major depressive disorders, greater educational attainment, and higher cognitive performance, suggesting overlapping genetic architectures. The genetic variants modulate the function of chromatin remodeling and synaptic proteins that influence the connectivity of neuronal circuits and, in interaction with the environment of each individual, the subsequent cognitive and personal trajectory of the child. Overall, this genetic heterogeneity mirrors the phenotypic diversity of autistic individuals and provides a helpful bridge between biomedical and neurodiversity perspectives. We propose that participative and multidisciplinary research should use this information to understand better the assessment, treatments, and accommodations that individuals with autism and families need.
Store-Operated Calcium Channels in the Nervous System
Authors: Korshunov Kirill S. , Prakriya Murali
Published: November 2024

Store-operated Ca2+ entry (SOCE) is a widespread mechanism of cellular Ca2+ signaling that arises from Ca2+ influx across the plasma membrane through the Orai family of calcium channels in response to depletion of intracellular Ca2+ stores. Orai channels are a crucial Ca2+ entry mechanism in both neurons and glia and are activated by a unique inside-out gating process involving interactions with the endoplasmic reticulum Ca2+ sensors, STIM1 and STIM2. Recent evidence indicates that SOCE is broadly found across all areas of the nervous system where its physiology and pathophysiology is only now beginning to be understood. Here, we review the growing literature on the mechanisms of SOCE in the nervous system and contributions to gene expression, neuronal excitability, synaptic plasticity, and behavior. We also explore the burgeoning links between SOCE and neurological disease and discuss therapeutic implications of targeting SOCE for brain disorders.
Adrenal epinephrine facilitates erythropoietin gene activation by hypoxia through β2 adrenergic receptor interaction with Hif-2α
Authors: Su Xiaoyu , Hildreth Matthew , Rapaka Srikar , Peng Ying-Jie , Nanduri Jayasri , Prabhakar Nanduri R.
Published: November 2024

Hypobaric hypoxia activates the sympathetic nervous system (SNS) and the erythropoietin ( EPO) gene. Whether SNS activation by hypoxia influences the EPO gene activation is an unresolved question. The present study demonstrates that adrenal epinephrine facilitates hypoxia-induced EPO gene activation through the interaction of β2 adrenergic receptors (β2 ARs) with the transcriptional activator HIF-2α.
Evaluation of Different Levels of Process Energy in Sorghum and Wheat‐Based Diets on the Growth Performance of Pacific White Shrimp, Litopenaeus vannamei
Authors: Graff Tucker , Ngo Trinh , Davis Donald Allen , Alavi Sajid
Published: November 2024

This research evaluated the effect of different levels of extrusion process energy during the production of wheat and sorghum‐based feeds on the growth performance and digestibility of Pacific white shrimp (Litopenaeus vannamei). Process energy consisted of mechanical and thermal components, which were both modulated via varying preconditioner steam addition. Diets were formulated to be isonitrogenous (36% protein) and isolipidic (8% fat), with three levels of thermal energy (TE) input during preconditioning (high, medium, and low). All diets showed increased starch gelatinization with increased TE, with the wheat‐based diets undergoing a greater degree of gelatinization than the sorghum‐based diets. There were no significant differences in final biomass, weight gain, feed conversion ratio (FCR), or survival among the different treatments. However, digestibility results showed that wheat‐based diets had significantly higher apparent digestibility coefficients (ADCs) for both protein and energy compared to sorghum‐based diets. Overall, increased starch gelatinization that correlated with greater digestibility was observed, but this effect was reduced in the sorghum‐based diets. These findings suggest that sorghum can be used as a viable alternative to wheat in shrimp feed without negatively impacting their growth performance, while also offering potential cost savings to producers.
Analysis and Prediction of Airfield Area Conflict Risk Under Dynamic Time‐Varying Network
Authors: Liu Linning , Wang Xinglong , He Min , Xu YanFeng
Published: November 2024

To ensure the safety of operations in the airfield area, it is crucial to address the increased conflict risks resulting from the growing number of vehicles and aircraft. Based on the complex network theory, this study takes aircraft and vehicles in the airfield area as nodes and selects five different indicators (average degree, average node weight, average weighted clustering coefficient, network density, and network efficiency) to characterize the operation state of the airfield area, so as to identify conflict risks. Building on this framework, an ATT‐Bi‐LSTM innovation prediction model based on LSTM network architecture is established to forecast the evolution of network indicators over time. By leveraging the algorithm to predict the temporal evolution of indicators, valuable insights into the future evolution of conflict risk can be gleaned from the prediction results. Real operational data from Xi’an Xianyang Airport are utilized as a demonstrative example in this study. The results of the experiments illustrate that the analytical approach proposed in this study achieves a precise identification of the indicators. The experimental results are then compared with data from other predictive models that operate on the same data set. Compared to alternative prediction models, the accuracy is increased by nearly 10%, reaching 89.78%. The results of the study help to accurately identify conflict risks in the airfield area in advance and provide strategic conflict avoidance strategies for relevant staff. This is essential to ensure the security of airfield area.
Early Onset of Wilson’s Disease and Possible Role of Disease‐Modifying Genes: A Case Report and Literature Review
Authors: La Rosa Alessandro , Covone Angela Elvira , Coviello Domenico , Arrigo Serena , Ferro Jacopo , Gandullia Paolo , Madeo Annalisa
Published: November 2024

Wilson’s disease (WD) is a rare autosomal recessive disorder caused by mutations in the ATP7B gene, resulting in copper accumulation. Symptoms rarely appear before the age of 5, almost never before 3. The phenotypic variability of WD suggests the presence of modifying factors, making early diagnosis challenging. We present a case of symptomatic WD in a toddler, emphasizing the importance of considering WD in differential diagnoses and exploring genetic modifiers influencing disease onset. Clinical and laboratory assessments, including liver biopsy, were performed on a 4.2‐year‐old boy presenting with hypertransaminasemia and mild hepatomegaly. Histological evaluation revealed chronic hepatitis with fibrosis and severe steatosis, indicating long‐standing active disease. Genetic analysis identified a missense variant and a 15‐nucleotide deletion in the 5′ UTR promoter region of the ATP7B gene, confirming the WD diagnosis. Additionally, homozygosity for the HFE H63D variant was detected, with transferrin saturations at the upper limit of normal. The patient’s clinical management included a trial of D‐penicillamine, discontinued due to side effects, followed by successful zinc acetate therapy. This case underscores the consideration of WD in the differential diagnosis of toddlers. The Ferenci‐Leipzig score remains a valid diagnostic tool for WD even in the presence of a single ATP7B variant, although extended genetic analysis should still be considered. Normal ceruloplasmin levels do not rule out WD. Environmental, epigenetic, and genetic factors appear to influence the WD phenotype; HFE variants may act as modifiers given the link between iron and copper homeostasis, possibly explaining the early symptomatic onset in our patient.
Optimizing Seed Germination of Acacia crassicarpa by Scarification and Plasma Fine Bubbles Treatments
Authors: Sudrajat Dede J. , Rustam Evayusvita , Yulianti  , Widyani Nurin , Putri Kurniawati P. , Yuniarti Naning , Nurhasybi  , Widyanti Salsabila , Purwanto Y. Aris , Yuskianti Vivi , Zanzibar M.
Published: November 2024

The availability of appropriate methods to increase germination capacity (GC), thereby increasing the growth and vigor of seedlings in the nursery, plays an important role in the success of tree planting in industrial plantation forests. The aim of this research was to determine the effect of scarification and plasma fine bubbles (PFBs) treatments on the GC, viability, and vigor of Acacia crassicarpa A. Cunn. Ex Benth. seeds, one of the important acacias trees in industrial plantation forests. A completely randomized design with two factors, namely, scarification (soaking in 80°C to cold water for 24 h and 96% H2SO4 for 15, 20, and 25 min) and PFBs water treatment with ozone concentrations of 2 and 3 ppm for 5 and 10 min was used. Our study showed that the combination of scarification with H2SO4 solution for 25 min and 3 ppm PFBs water for 10 min gave the highest GC (90.75%), germination rate (GR) (20.28% days−1), and germination value (GV) (1.41). This combination also provided better results compared with methods widely used in industrial plantation forests by increasing GC 76.2%, GR 103.1%, and GV 291.7% and increasing hypocotyl length from 3.76 cm to 6.15 cm, radicle length from 2.24 cm to 6.31 cm, normal seedling length from 6.11 cm to 12.20 cm, and vigor index (VI) from 1.2 to 11.07 compared with control. This combination has been proven to increase germination, growth, and vigor of A. crassicarpa seeds; therefore, this treatment combination is recommended for use at the operational level of industrial plantation forests.
Lifestyle, Working Conditions, and Quality of Life Among Dentists in Kazakhstan
Authors: Syzdykova Azhar , Toguzbayeva Karlygash , Syzdykova Aiman , Bekkazinova Danara , Qumar Ainur B. , Abikulova Akmaral , Izekenova Aigulsum
Published: November 2024

Background: The study of working conditions and the quality of life (QoL) of medical workers has not lost its relevance worldwide. This highlights the need to understand the many aspects of life that may characterize physician performance and satisfaction with working conditions. This is extremely important for providing quality and safe medical care. This research aims to study dentists’ lifestyles and working conditions in the Republic of Kazakhstan and the impact of these indicators on their QoL.

Methods: This article presents the results of a cross‐sectional survey of a sociological questionnaire conducted with the participation of 254 dentists in Kazakhstan.

Results: Only a third of dentists follow a healthy lifestyle. In total, 39% of dentists currently smoke, and 24% drink alcohol. Dentists with more than 20 years of experience have a worse QoL and have the lowest scores in all domains compared to dentists with less experience. The lowest score was scored for mental health (mean = 51.81). On all scales, dentists who worked more than 40 h a week reported decreased QoL; the lowest score was in the “mental health” domain (mean = 52.80).

Conclusion: The QoL of dentists in Kazakhstan is negatively affected by their working hours and long working experience. Measures are necessary to improve their working conditions, work schedule planning, and mental health.
Analysis of Influencing Factors Related to Health Literacy of Diabetic Patients: A Survey Based on DHLEIS
Authors: Chen Yalan , Wang Zepeng , Jiang Fangyuan , Shi Junyi , Jiang Kui
Published: November 2024

Purpose: This study is aimed at investigating health literacy (HL) among diabetes mellitus (DM) patients using a comprehensive, scientific, feasible, and suitable HL assessment indicator system tailored for the diabetic population in mainland China and systematically analyzing the factors influencing HL in this population.

Methods: The Delphi expert consultation method was employed to initially draft and refine the Diabetes Health Literacy Evaluation Indicator System (DHLEIS). The reliability and representativeness of the indicator system were tested through metrics including the active coefficient, authority degree, and coordination degree. A HL survey questionnaire for diabetic patients was developed based on DHLEIS and administered to diabetic patients across five hospitals in Nantong and Yancheng cities, Jiangsu Province. The random forest method was utilized to deeply analyze the impact of various factors on HL and its four dimensions and to identify the core influencing factors.

Results: Analysis of 707 questionnaires based on the DHLEIS revealed that nine factors—age, sex, body shape, income, exercise, education level, duration of DM, whether insulin is injected, and the number of cohabitants—significantly impact the HL levels. Among these, age, duration of DM, education level, and number of cohabitants were particularly influential across the four dimensions of health knowledge, awareness, behavior, and skills. Factors related to health knowledge and skills were the most significant contributors to overall HL.

Conclusions: The multidimensional analysis of factors influencing HL offers valuable insights into characterizing varying levels of HL among diabetic patients. This approach supports targeted cognitive improvements and the effective enhancement of health skills, ultimately leading to better health outcomes.
An Exploration of the Impact of a Work Integrated Learning Community (WILCo) Model on Students’ Placement Experiences and Intention to Remain: A Longitudinal, Exploratory Study
Authors: Whiteing Nicola , Walker Felicity , Aggar Christina , Bowen Karen
Published: November 2024

Background: Work Integrated Learning experiences contribute to nursing student attrition and preparation for practice. A predicted global shortage of nurses requires healthcare organisations and education providers to review and implement new models of Work Integrated Learning to best prepare and retain nursing students for practice. Work Integrated Learning opportunities within the same healthcare facility may improve nursing student’s clinical learning experiences.

Objectives: To explore student experiences during a Work Integrated Learning Community (WILCo) model and their intention to remain working at the healthcare facility upon graduation.

Design: A longitudinal, exploratory, qualitative research study utilising focus groups.

Settings: Tertiary teaching hospitals in regional New South Wales Australia.

Participants: A convenience sample of Bachelor of Nursing students (n = 26) studying at a regional university in Australia who were participating in the WILCo program were invited to participate in this research.

Methods: Focus groups were conducted with students after the completion of their Work Integrated Learning experiences (n = 16) during their degree. Data were thematically analysed using Braun and Clarke’s framework.

Results: Five themes emerged: ‘learning local’, ‘belonging’, ‘collegiality’, ‘piecing together the puzzle’: ‘theory and practice’ and ‘looking to the future’.

Conclusion: Work Integrated Learning opportunities at the same healthcare facility had a positive effect on student’s sense of belonging and collegiality. The continuity of the placement allowed familiarity with complex systems, processes and healthcare staff, which reduced stressors. This collaborative Work Integrated Learning initiative was successful in improving the quality of the student learning experience and their intention to seek employment within the healthcare facility.
Deflection Prediction of a Rail‐Cum‐Road Suspension Bridge Under Multiple Operational Loads With Improved GPR and FSF
Authors: Liu Xingwang , Sun Zhen , Guo Tong
Published: November 2024

The deformation of the main girder is an important manifestation of the overall stiffness of suspension bridges, which is essential for assessing bridge performance. Nevertheless, it is difficult to achieve satisfied prediction without fully considering the overall operational loads. To this end, this paper proposes a method to predict the deflection considering multiple operational loads using the monitoring data of a high‐speed rail‐cum‐road suspension bridge. Initially, an improved Gaussian process regression (GPR) model utilizing Bayesian optimization was employed to predict the deformation of the main girder under the condition of nontrain loads. Furthermore, the distinct contributions of temperature, wind, and vehicle load were analyzed. Subsequently, based on the strain and deflection induced by train loads, the sum of sinusoids method was proposed to construct fitting and shape function (FSF) for predicting the main girder deformation under the influence of train loads. Ultimately, the deformation considering overall loads was obtained by adding the deformation under the nontrain and train loads, and the predicted deformation result was verified using the measured data. When compared to other state‐of‐the‐art machine learning algorithms, namely, artificial neural network (ANN), support vector machine (SVM), and decision tree (DT), the improved GPR demonstrates the highest accuracy in predicting the deformation of the main girder under nontrain loads with R2 of 0.9478. In addition, the proposed sum of sinusoids FSF method accurately predicted the deformation of the main girder caused by train loads, with R2 of 0.934. The deformation of the main girder under the influence of overall loads can lay a foundation for the early warning and evaluation of the suspension bridges.
Supplementary Data 1 from Functional Impact of Genomic Complexity on the Transcriptome of Multiple Myeloma
Authors: Ziccheddu Bachisio , Da Vià Matteo C. , Lionetti Marta , Maeda Akihiro , Morlupi Silvia , Dugo Matteo , Todoerti Katia , Oliva Stefania , D'Agostino Mattia , Corradini Paolo , Landgren Ola , Iorio Francesco , Pettine Loredana , Pompa Alessandra , Manzoni Martina , Baldini Luca , Neri Antonino , Maura Francesco , Bolli Niccolò
Published: November 2024

Tables, figures, methods and references
Supplementary Figure 3 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms In Vitro and in a First-In-Human Phase I Clinical Trial
Authors: Schwenzer Hagen , De Zan Erica , Elshani Mustafa , van Stiphout Ruud , Kudsy Mary , Morris Josephine , Ferrari Valentina , Um In Hwa , Chettle James , Kazmi Farasat , Campo Leticia , Easton Alistair , Nijman Sebastian , Serpi Michaela , Symeonides Stefan , Plummer Ruth , Harrison David J. , Bond Gareth , Blagden Sarah P.
Published: November 2024

Figure S3 related to figure 4: HINT1 expression across selected cancer types. A) Examples histochemical staining of HINT1 in various types of cancer cells. B) Quantification of HINT1 expression in various types of cancer. The proportion of HINT1 positivity scored by the Allred score, which is combination of proportion of positive cells and the predominant intensity of the protein expression.
Figure 3 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms In Vitro and in a First-In-Human Phase I Clinical Trial
Authors: Schwenzer Hagen , De Zan Erica , Elshani Mustafa , van Stiphout Ruud , Kudsy Mary , Morris Josephine , Ferrari Valentina , Um In Hwa , Chettle James , Kazmi Farasat , Campo Leticia , Easton Alistair , Nijman Sebastian , Serpi Michaela , Symeonides Stefan , Plummer Ruth , Harrison David J. , Bond Gareth , Blagden Sarah P.
Published: November 2024

Validation of top hits from genome-wide haploid screen. A, HINT1 was deleted in HAP1 cells using CRISPR/Cas9 technology, as shown by Western blot analysis of HINT1 KO cells using specific antibodies to HINT1. WT and KO cells were treated with either NUC-7738 or 3′-dA. IC50 values were determined and the fold change between KO and WT cells was calculated. B, Single-cell–derived clonal knockouts for HINT1 (KO1 and KO5) and 2 WT isogenic cell lines. Western blot analysis of HINT1 KO cells using specific antibodies to HINT1 is shown. Following treatment with NUC-7738 or 3′-dA, IC50 values were determined and the fold change between KO and WT cells were calculated. C, Correlation between IC50 of NUC-7738 or 3′-dA and mRNA abundance in different NCI-60 cells is given for ADA, ADK, and HINT1. mRNA expression levels are given as z-score calculated across all NCI-60 cell lines. mRNA expression levels were obtained from CellMinerTM v2.4.2. D, Western blot validation of siRNA-mediated HINT1 knockdown in renal cancer cell lines. WT and knockdown cells were treated with either NUC-7738 or 3′-dA. Graph shows the fold change in percentage of viable cells normalized to control (n = 3) after treatment with NUC-7738.
Supplementary Table 4 from Tumor Cell IDO Enhances Immune Suppression and Decreases Survival Independent of Tryptophan Metabolism in Glioblastoma
Authors: Zhai Lijie , Bell April , Ladomersky Erik , Lauing Kristen L. , Bollu Lakshmi , Nguyen Brenda , Genet Matthew , Kim Miri , Chen Peiwen , Mi Xinlei , Wu Jennifer D. , Schipma Matthew J. , Wray Brian , Griffiths John , Unwin Richard D. , Clark Simon J. , Acharya Rajesh , Bao Riyue , Horbinski Craig , Lukas Rimas V. , Schiltz Gary E. , Wainwright Derek A.
Published: November 2024

Supplementary Table 4. Mass spectrometry parameters for detecting CFH and FHL-1 in plasma.
Supplementary Figure 2 from Tumor Cell IDO Enhances Immune Suppression and Decreases Survival Independent of Tryptophan Metabolism in Glioblastoma
Authors: Zhai Lijie , Bell April , Ladomersky Erik , Lauing Kristen L. , Bollu Lakshmi , Nguyen Brenda , Genet Matthew , Kim Miri , Chen Peiwen , Mi Xinlei , Wu Jennifer D. , Schipma Matthew J. , Wray Brian , Griffiths John , Unwin Richard D. , Clark Simon J. , Acharya Rajesh , Bao Riyue , Horbinski Craig , Lukas Rimas V. , Schiltz Gary E. , Wainwright Derek A.
Published: November 2024

Supplemental Figure 2. Histological evaluation of tumor progression and confirmation of IDO-mGFP expression in brain tumors.
Supplementary fig 1 from Ovarian Cancer–Specific BRCA-like Copy-Number Aberration Classifiers Detect Mutations Associated with Homologous Recombination Deficiency in the AGO-TR1 Trial
Authors: Schouten Philip C. , Richters Lisa , Vis Daniel J. , Kommoss Stefan , van Dijk Ewald , Ernst Corinna , Kluin Roelof J.C. , Marmé Frederik , Lips Esther H. , Schmidt Sandra , Scheerman Esther , Prieske Katharina , van Deurzen Carolien H.M. , Burges Alexander , Ewing-Graham Patricia C. , Dietrich Dimo , Jager Agnes , de Gregorio Nikolaus , Hauke Jan , du Bois Andreas , Nederlof Petra M. , Wessels Lodewyk F. , Hahnen Eric , Harter Philipp , Linn Sabine C. , Schmutzler Rita K.
Published: November 2024

Supplemental Figure 1. CONSORT-like flow diagram of the AGO-TR1 trial. The sample for BRCA-like classification has been selected with the aim to enrich for germline (g) and somatic (s) mutation status.
Figure S6 from Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Li Binghao , Li Guoqi , Yan Xiaobo , Zhu Dan , Lin Patrick P. , Wang Zenan , Qu Hao , He Xuexin , Fu Yanbiao , Zhu Xiuliang , Lin Peng , Zhang Jiangnan , Li Xiaoya , Dai Hui , Chen Huabiao , Poznansky Mark C. , Lin Nong , Ye Zhaoming
Published: November 2024

Figure S6
Data from First-In-Human Phase I Study of a Next-Generation, Oral, TGFβ Receptor 1 Inhibitor, LY3200882, in Patients with Advanced Cancer
Authors: Yap Timothy A. , Vieito Maria , Baldini Capucine , Sepúlveda-Sánchez Juan Manuel , Kondo Shunsuke , Simonelli Matteo , Cosman Rasha , van der Westhuizen Andre , Atkinson Victoria , Carpentier Antoine F. , Löhr Mario , Redman Rebecca , Mason Warren , Cervantes Andres , Le Rhun Emilie , Ochsenreither Sebastian , Warren Louise , Zhao Yumin , Callies Sophie , Estrem Shawn T. , Man Michael , Gandhi Leena , Avsar Emin , Melisi Davide
Published: November 2024

AbstractPurpose:
A novel, selective, next-generation transforming growth factor beta (TGFβ) receptor type-1 small molecule inhibitor, LY3200882, demonstrated promising preclinical data. This first-in-human trial evaluated safety, tolerability, recommended phase II dose (RP2D), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of LY3200882 as monotherapy or with other anticancer agents in patients with advanced cancer.
Patients and Methods:
This phase I multicenter study of oral LY3200882 (NCT02937272) comprised dose escalation, monotherapy expansion in grade 4 glioma, and combination therapy in solid tumors (LY3200882 and PD-L1 inhibitor LY3300054), pancreatic cancer (LY3200882, gemcitabine, and nab-paclitaxel), and head and neck squamous cell cancer (LY3200882, cisplatin, and radiation).
Results:
Overall, 139 patients with advanced cancer were treated. The majority (93.5%) of patients experienced ≥1 treatment-emergent adverse events (TEAE), with 39.6% LY3200882-related. Grade 3 LY3200882-related toxicities were only observed in combination therapy arms. One patient in the pancreatic cancer arm experienced cardiovascular toxicity. The LY3200882 monotherapy RP2Ds were established in two schedules: 50 mg twice a day 2-weeks-on/2-weeks-off and 35 mg twice a day 3-weeks-on/1-week-off. Four patients with grade 4 glioma had durable Revised Assessment in Neuro Oncology (RANO) partial responses (PR) with LY3200882 monotherapy (n = 3) or LY3200882-LY3300054 combination therapy (n = 1). In treatment-naïve patients with advanced pancreatic cancer, 6 of 12 patients achieved Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 PR and 3 of 12 patients demonstrated stable disease, for an overall 75% disease-control rate with the combination of LY3200882, gemcitabine, and nab-paclitaxel.
Conclusions:
LY3200882 as monotherapy and combination therapy was safe and well tolerated with preliminary antitumor activity observed in pancreatic cancer. Further studies to evaluate the efficacy of LY3200882 with gemcitabine and nab-paclitaxel in advanced pancreatic cancer are warranted.
Treatment of Chronic-Relapsing Pitted Keratolysis with Glycopyrronium Bromide Cream: Case Report
Authors: Veraldi Stefano , Schianchi Rossana , Aromolo Italo Francesco , Nazzaro Gianluca
Published: November 2024

Introduction: Pitted keratolysis (PK) is a superficial bacterial infection located almost exclusively on the soles. The most important predisposing factor is hyperhidrosis. PK is characterized by small, isolated or confluent, crateriform, noninflammatory pits. Maceration and malodor are the two most important signs and symptoms. The therapy of PK is very often unsatisfactory. Case Presentation: Two patients with chronic-relapsing PK were successfully treated with a cream containing 1% glycopyrronium bromide, a new topical anticholinergic with anti-hyperhidrosis action. Conclusions: Although our experience is currently based on only 2 patients, glycopyrronium bromide cream can be taken into consideration for prevention of chronic-relapsing PK.
Coronary Artery Disease and Microvascular Ischemia in Patients with Cardiac Amyloidosis
Authors: Itzhaki Ben Zadok Osnat , Vaxman Iuliana , Hoss Sara , Talmor-Barkan Yeela , Steinmetz Tali , Raanani Pia , Kornowski Ran , Hamdan Ashraf
Published: November 2024

Introduction: The prevalence of pre-existing obstructive coronary artery disease (CAD) and the occurrence of anginal chest pain as a presenting symptom in patients with light chain (AL) and transthyretin (ATTR) cardiac amyloidosis (CA) are undetermined.
Methods: A single-center analysis of clinical, laboratory, imaging and angiographic characteristics of CA cohort.
Results: Included were 98 CA patients (43 AL, 47 wtATTR, 8 mutant ATTR). Eighteen patients (18%) had pre-existing obstructive CAD at the time of CA diagnosis. These patients were older and had worse left ventricular ejection fraction, yet revealed similar cardiac biomarkers’ levels. The 3-year survival rate was comparable between patients with versus without pre-existing CAD (p=0.974). Anginal chest pain was a presenting symptom of newly-diagnosed CA in 24% (n=19) of patients with no pre-existing CAD, 53% (n=10) of which had AL-CA. Two patients had an acute myocardial infarction. The prevalence of diabetes mellitus, dyslipidemia, hypertension and smoking was similar among CA patients presenting with versus without chest pain. Of the newly-diagnosed CA patients with no pre-existing CAD who underwent symptoms evaluation (n=37), 99mTc-Sestamibi myocardial perfusion scintigraphy demonstrated stress-induced perfusion defects in 45% (9/20) and normal study in 45% (9/20) of patients. Coronary evaluation revealed non-obstructive coronary artery lesions or normal coronaries in 75% of patients (18/24).
Conclusion: CA patients may initially present with anginal chest pain and myocardial perfusion defects which may reflect coronary microvascular ischemia. CA should be considered in the differential diagnosis of patients presenting with chest pain, non-obstructive CAD and elevated cardiac biomarkers.
The MAASWERP Study: An International, Comparative Case Study on Measuring Biomechanics of the Aged Murine Aorta
Authors: Neutel Cédric H.G. , van der Laan Koen W.F. , Wesley Callan D. , Krüger Dustin N. , Pencheva Margarita G. , Schalkwijk Casper G. , De Meyer Guido R.Y. , Martinet Wim , Delhaas Tammo , Reesink Koen D. , Giudici Alessandro , Guns Pieter-Jan , Spronck Bart
Published: November 2024

Introduction: Arterial stiffening is a hallmark of vascular ageing, and unravelling its underlying mechanisms has become a central theme in the field of cardiovascular disease. While various techniques and experimental setups are accessible for investigating biomechanics of blood vessels both in vivo and ex vivo, comparing findings across diverse methodologies is challenging. Methods: Arterial stiffness in the aorta of adult (5 months) and aged (24 months) wild-type C57Bl/6J mice was measured in vivo, after which ex vivo biomechanical evaluation was performed using the Rodent Oscillatory Tension Setup to study Arterial Compliance (ROTSAC; University of Antwerp, Belgium) and the DynamX setup (Maastricht University, The Netherlands). Stiffness of aortic tissue was measured in both absence and presence of activated smooth muscle cells (i.e., contraction). Measurements in both setups were conducted in parallel with matched protocols and identical buffers and chemicals. Results: Overall, both methods revealed age-related increased aortic stiffness, although parameters of aortic mechanics showed different numerical values, suggesting that results are not directly interchangeable between methods. Surprisingly, smooth muscle cell contraction had opposing effects between the setups. Indeed, smooth muscle cell contraction increased arterial stiffness in the ROTSAC but decreased stiffness in the DynamX. These opposing effects could be attributed to how the two setups differentially load the collagen fibres in the arterial wall, ex vivo. Conclusion: Overall, this study provided critical insights into how different experimental setups can influence the interpretation of aortic biomechanics, emphasizing the need for careful consideration and contextualization of results based on the methodology used.
Psychological Mediators of the Association between Obesity and Symptoms of Depression, Anxiety, and Stress
Authors: Henriques Joana , Afreixo Vera , Unterrainer Human , Senra Hugo
Published: November 2024

Introduction: There is still paucity of knowledge about which factors can mediate the link between obesity and mental health problems. This study aimed to investigate psychological mediators of the association between different weight profiles (healthy, overweight, and obesity) and symptoms of depression, anxiety, and stress. Methods: A sample of 407 adults (≥18 years old) with different weight profiles recruited from general population was assessed for symptoms of depression, anxiety, and stress, and dimensions of emotion regulation and body investment/body image. Robust regression and robust mediation analyses were employed to investigate predictors and mediators of mental health outcomes in relation to different weight profiles. Results: Body investment difficulties in relation to body image and body care, and emotion regulation difficulties related to a tendency towards negative secondary responses to negative emotions, and/or denial of distress, significantly mediated the association between obesity and symptoms of depression. The association between obesity and symptoms of anxiety and stress was significantly mediated by body investment difficulties related to body image concerns. Conclusions: The current study brings evidence on specific dimensions of emotion regulation and body image that play a key role for the co-occurrence of mental health problems in individuals with obesity.
Análise longitudinal das escolhas ocupacionais dos jovens após o nível médio
Authors: Mariano Francisca Zilania , Arraes Ronaldo Albuquerque
Published: November 2024

Este estudo busca contribuir com a literatura ao identificar os condicionantes das escolhas ocupacionais pelos jovens, após conclusão do ensino médio, até então, não abordado por outros autores. Além disso, diferentemente da maioria dos estudos sobre alocação de tempo entre estudo e trabalho, a análise é conduzida em nível longitudinal, após cruzamento de quatro bases de dados distintas. Os resultados permitiram concluir que: i) os jovens advindos de escolas públicas regulares e pertencentes a famílias beneficiárias do Programa Bolsa Família apresentam maiores probabilidades de não ingressarem no ensino superior ou no mercado de trabalho formal; ii) os alunos que concluíramem escolas profissionalizantes apresentam características observáveis e não observáveis que favorecem o ingresso no ensino superior e/ou no mercado de trabalho.
Ex-vivo evaluation of a percutaneous thread technique to palmar/plantar annular desmotomy in horses
Authors: Silva Nathalia Felício da , Souza Anderson Fernando de , Zoppa André Luis do Valle De
Published: November 2024

Palmar/plantar annular desmotomy (PAD) is a surgical procedure to mitigate pain, lameness, and other clinical manifestations of annular ligament syndrome. This study aimed to describe a minimally invasive technique for PAD and evaluate potential damage to adjacent structures in 15 cadaveric limbs from sound horses (forelimb = 6 and hindlimb = 9). A 6 USP polyglycolic acid thread was positioned around the palmar/plantar annular ligament (PAL) on both sides of the limbs through two incisions (proximal and distal to PAL) through the digital sheath and subcutaneous tissue. Kelly forceps, Gerlach or Obwegeser needles were used to thread placement. A back-and-forth motion allowed the thread to cut the ligament until it exited through the proximal skin incision, and the time was registered. The degree of PAL section and tissue injuries were evaluated. The section of the ligament was complete in all limbs. However, 30% (10/30) of the procedures produced iatrogenic injuries on adjacent structures regardless of the instrument used (p > 0.1). There was a higher frequency of lesions in the neurovascular bundle (NVB) on the medial side regardless of the limb (p = 0.068). The odds of injury in the NVB were correlated to side (lateral or medial (p = 0.042) and limb (hind or forelimb) (p = 0.065) by logistic regression. The Gerlach needle had a shorter execution time than the Kelly forceps (p = 0.003). The percutaneous approach to PAD in specimens was practical, quick, and easy to perform. However, this posed a potential chance of iatrogenic trauma to the surrounding tissue. Although they are all reasonable options, the Obwegeser needle was more efficient for applying the thread than the others.
Mineralocorticoid Receptor Antagonists in Heart Failure: An Update
Authors: Ferreira João Pedro , Pitt Bertram , Zannad Faiez
Published: November 2024

Spironolactone, a steroidal mineralocorticoid receptor antagonist (MRA), has been used to treat patients with heart failure (HF) for more than half a century. Spironolactone improved outcomes in patients with severely symptomatic HF with reduced ejection fraction, and later, eplerenone expanded the benefits to patients with mildly symptomatic HF with reduced ejection fraction and myocardial infarction complicated by HF. Spironolactone reduced HF events in some patients with HF with preserved ejection fraction, but the results were not generalizable to all patients with HF with preserved ejection fraction. More recently, the nonsteroidal MRA finerenone improved the HF outcomes of patients with HF with preserved ejection fraction, expanding the benefits previously seen among patients with diabetes and albuminuric chronic kidney disease. The use of MRAs has been limited due to excessive concern about hyperkalemia. Education about the limited true risk associated with hyperkalemia, and about how to predict, prevent, and manage hyperkalemia, may lead to wider acceptability and use of these agents. Several ongoing trials are testing steroidal and nonsteroidal MRAs in HF populations. In this review, we perform a critical appraisal of MRA use in HF populations and point toward future directions.
Morphology of the egg-case and larva of Paracymus aeneus (Germar) (Coleoptera: Hydrophilidae)
Authors: MINOSHIMA YÛSUKE N. , WATANABE KOHEI
Published: November 2024

The generic and species identity of previously described larva of Paracymus aeneus (Germar, 1824), the type species of the genus Paracymus Thomson, 1867, has been a subject of controversy owing to their morphological similarity to the genus Anacaena Thomson, 1859. In this study, we describe morphology of the egg-case and all three instar larvae of P. aeneus based on Japanese specimens obtained through rearing and provide the biological information on the species under rearing conditions. The morphology of the larvae corresponds with that of known Paracymus larvae rather than Anacaena. Consequently, larvae previously described as P. aeneus do not belong this species. Therefore, this is the first description of the immature stages of P. aeneus.
Insights into Cloud Albedo Biases from a Cloud-Controlling Factor Framework
Authors: Blanco Joaquín E. , Caballero Rodrigo , Sherwood Steven , Alexander Lisa
Published: November 2024

A long-standing and pervasive problem in climate modeling is the proper representation of cloud albedo over the Southern Ocean (SO). In this study, we investigate the causes of SO cloud albedo biases using phase 6 of the Coupled Model Intercomparison Project (CMIP6) simulations and a cloud-controlling factor approach on daily time scales. Cloud albedo, computed from upwelling and downwelling shortwave radiation at the surface and top of the atmosphere, is averaged into bins of vertical velocity, surface wind, and sea surface temperature. The performance of 15 models in both atmosphere-only and ocean-coupled configurations is evaluated against Clouds and the Earth’s Radiant Energy System (CERES) satellite retrievals in combination with ERA5 reanalysis for the 2000–14 period. We find that the SO cloud biases maximize in the 50°–65° oceanic band and that models tend to underestimate SO cloud reflectivity for cold conditions and weak surface winds. In turn, descent (ascent) conditions are consistently underestimated (overestimated) across models for both hemispheres in the same latitude band. With a very similar approach, we evaluate how models represent the observed cloud albedo hemispheric asymmetry over oceans, which also maximizes in the 50°–65° band. The sign of the asymmetry is consistently predicted by all models, many of which also predict a similar magnitude to observations. However, this is also a consequence of compensating global biases as individually most models tend to either overpredict or underpredict cloud albedo in both hemispheres. We propose that surface temperatures less than 4°C are important in explaining SO bias in cloud albedo and that they also partly explain the observed hemispheric asymmetry. Further, we hypothesize that the 4°C threshold sets a hemispheric asymmetry in cloud phase.
Book review: Ravi Dutt Bajpai, Civilization-States of China and India—Reshaping the World Order
Authors: Narayanan Raviprasad
Published: November 2024

Ravi Dutt Bajpai, Civilization-States of China and India—Reshaping the World Order. Bloomsbury, 2024 pp. 268, ISBN: HB 978-93-56401-98-3, eBook: 978-93-56402-00-3.
Discriminant Validity of Interval Response Formats: Investigating the Dimensional Structure of Interval Widths
Authors: Kloft Matthias , Heck Daniel W.
Published: November 2024

In psychological research, respondents are usually asked to answer questions with a single response value. A useful alternative are interval response formats like the dual-range slider (DRS) where respondents provide an interval with a lower and an upper bound for each item. Interval responses may be used to measure psychological constructs such as variability in the domain of personality (e.g., self-ratings), uncertainty in estimation tasks (e.g., forecasting), and ambiguity in judgments (e.g., concerning the pragmatic use of verbal quantifiers). However, it is unclear whether respondents are sensitive to the requirements of a particular task and whether interval widths actually measure the constructs of interest. To test the discriminant validity of interval widths, we conducted a study in which respondents answered 92 items belonging to seven different tasks from the domains of personality, estimation, and judgment. We investigated the dimensional structure of interval widths by fitting exploratory and confirmatory factor models while using an appropriate multivariate logit function to transform the bounded interval responses. The estimated factorial structure closely followed the theoretically assumed structure of the tasks, which varied in their degree of similarity. We did not find a strong overarching general factor, which speaks against a response style influencing interval widths across all tasks and domains. Overall, this indicates that respondents are sensitive to the requirements of different tasks and domains when using interval response formats.
Incentives to Comply with the Minimum Wage in the United States and the United Kingdom
Authors: Stansbury Anna
Published: November 2024

There is substantial evidence of minimum wage non-compliance in the United States and the United Kingdom. In this article, the author compiles new, comprehensive data on the costs that minimum wage violators incur when non-compliance is detected. In both countries, the costs violators face are often little more than the money they saved by underpaying. To have an incentive to comply under existing penalty regimes, typical US firms would thus have to expect a 47% to 83% probability of detection by the Department of Labor (DOL), or a 25% probability of a successful Fair Labor Standards Act (FLSA) suit. In the United Kingdom, typical firms would have to expect a 44% to 56% probability of detection. Actual probabilities of detection are substantially lower than this for many firms and would likely remain so even with realistic increases in enforcement capacity. Improved enforcement alone is thus insufficient: Expected penalties must also substantially increase to ensure that most firms have an incentive to comply.
Multisource sensors navigation methodology applied to ADAS testing platform vehicle
Authors: Cheng Zhuo , Xu Lin , Sun Liyang , Xu Chuyong
Published: November 2024

This study addresses sensor signal loss in Advanced Driver Assistance Systems (ADAS) testing when switching between open and tunnel test sites. Current methods require pausing and switching sensor devices, disrupting the testing process. This study proposes a multisource sensor integrated navigation algorithm based on the Interacting Multiple Model (IMM) framework, using GNSS/INS error state Kalman filter (ESKF) positioning in open areas and UWB/INS ESKF positioning in GNSS failure scenarios, like tunnels. An Interacting Multiple Model based on Adaptive Transition Probability Matrix (ATPM-IMM) algorithm is introduced, enabling adaptive Markov jump probability for target tracking. The method ensures positioning accuracy using low-cost UWB and IMU and achieves seamless sensor source switching. Compared with traditional GNSS/INS and UWB/INS methods, the proposed approach improves accuracy by 31.17% and 41.23%, respectively, providing a reference for future multisource sensor fusion positioning research.