bluuebunny/crossref_metadata_2025 huggingface dataset:
A Welfare Test for Sharing Health Data
Authors: Sen Anindya , Chen Helen , Grossman Maura R. , Tsao Shu‐Feng
Published: October 2024

Machine learning and artificial intelligence methods are being increasingly used in the analysis of patient level and other health data, resulting in new insights and significant societal benefits. However, researchers are often denied access to sensitive health data due to concerns on privacy and security breaches. A key reason for reluctance in data sharing by data custodians is the lack of a specific legislative or other methodological framework in balancing societal benefits against costs from potential privacy breaches. Consistent with traditional cost–benefit analysis and the use of Quality Adjusted Life Years (QALYs), this study proposes an economic test that would enable Research Ethics Boards (REBs) to assess the benefits versus risks of data sharing. Our test can also be used to assess whether REBs employ reasonable effort to protect individual privacy and avoid tort liability. Constructing an acceptable welfare test for health data sharing will also lead to a better understanding of the value of data.
Is Warm‐Up Preservation Modulated by Biological Maturation and Sex? Effects on Lower Limbs Performance
Authors: Cuenca‐Fernández Francisco , Ruiz‐Navarro Jesús J. , Arellano Raúl , Marko Đurović , Stojanović Nikola
Published: October 2024

Children and adults may react differently to warm‐up preservation due to different physical characteristics. This study aimed to: (i) assess the impact of different rewarm‐up routines in swimmers during a transition phase (20–25 min), including passive rest (SWU) or dynamic activities (RWU), on countermovement jump and swimming start performances, and (ii) explore potential RWU adaptations considering maturity offset (peak height velocity—PHV) and sex. Performance was analyzed using mixed effect ANCOVA, considering protocol, maturity offset (pre‐PHV, mid‐PHV, post‐PHV, and adv. post‐PHV), and sex. Results favored RWU over SWU with substantial magnitudes for jump height: pre‐PHV (min‐20, ES = 1.21; min‐25, ES = 1.65), mid‐PHV (min‐20, ES = 1.23; min‐25, ES = 1.14), post‐PHV (min‐20, ES = 1.37; min‐25, ES = 0.73), and adv. post‐PHV (min‐20, ES = 1.03; min‐25, ES = 0.65). Significant interactions at 25 min (p = 0.033, 0.047) showed that RWU outperformed SWU, especially in younger groups (pre‐PHV, mid‐PHV). RWU was superior to SWU for the reactive strength index at 20 min (p = 0.042) and 25 min (p = 0.047), with females having lower RSI than males at 20 min (p = 0.008, p = 0.015) and 25 min (p = 0.049) in later developmental stages. The flight distance (p = 0.009) and horizontal hip velocity (p = 0.014) revealed significant three‐way interactions, with the male adv. post‐PHV group responding better to RWU. Knee angular velocity was also higher after RWU, with male adv. post‐PHV group showing more pronounced improvements (p = 0.016). These results suggest that though RWU had higher influence in male adults, it is a valuable approach for varying ages athletes.
Shared decision‐making for patients with vaccine‐related concerns of blood transfusion: A single institution experience
Authors: Cho David J. , Klompas Allan M. , Gonzalez Jessica A. , Petsch Jamie L. , Burt Jen M. , Kor Daryl J. , Winters Jeffrey L. , van Buskirk Camille M. , Warner Matthew A.
Published: October 2024

Background

Some patients express concerns regarding receipt of allogeneic blood transfusions from donors potentially vaccinated against SARS‐CoV‐2 (COVID‐19). However, limited information exists about patients' expression of these concerns or how to address them during the blood transfusion consent process. In this study, we describe our experience of working collaboratively with patients with vaccine‐related transfusion concerns prior to elective surgery, summarizing treatment decisions and clinical outcomes.

Study Design and Methods

This observational descriptive study includes patients seen in our Bloodless Medicine and Surgery clinic between June 2022 and June 2024 for vaccine‐related transfusion concerns prior to elective surgery. A shared decision‐making framework was employed to foster conversation, share information, provide reassurance, reconcile conflict, and match preferences with available care options. Patient characteristics, treatment decisions, and surgical outcomes were reviewed and summarized.

Results

Thirty‐five patients were included, with median (1st, 3rd quartile) age of 61 (53, 69) years. Cardiac surgery was the most common type of surgery (29%). Twelve patients (34%) were anemic preoperatively, and all received preoperative treatment. After discussion with a Bloodless Medicine specialist, 24 (68.6%) decided to consent to the use of all blood products, 5 (14.3%) accepted only red blood cells, and 6 (17.1%) declined all blood products. Among 28 patients undergoing surgery, only 4 (14%) received allogeneic transfusion perioperatively.

Conclusion

Many patients concerned about the vaccination status of blood donors may ultimately consent to allogeneic blood products after shared decision‐making with a Bloodless Medicine specialist, highlighting the importance of patient empowerment and collaborative care.
Modeling the dependency structure between quality characteristics in multi-stage manufacturing processes with copula functions
Authors: Toktaş Pelin , Gebizlioğlu Ömer Lütfi
Published: October 2024

This study is about multi-stage manufacturing processes and their control by statistical process control modeling. There are two kinds of dependence structures in a multi-stage manufacturing process: one is the dependence between the stages of the process, and the other is the dependence between the concerned quality characteristics. This study employs state-space models to demonstrate the dependency structure between the process stages and uses the Kalman filter method to estimate the states of the processes. In this setup, copula modeling is proposed to determine the dependence structure between the quality characteristics of interest. A simulation study is conducted to assess the model's accuracy.  As a result, it was found that the model gives highly accurate predictions according to the mean absolute percentage error (MAPE) criteria (<10%).
Evidence on the accreditation of health professionals’ education in the WHO Africa region: a scoping review protocol
Authors: Nakidde Catherine , Marletta Debora , McGivern Gerry , O’Keeffe Catherine , Griffin Ann
Published: October 2024

Objective:

This scoping review aims to map and examine the extent and type of available evidence on health professionals’ education accreditation within Africa.

Introduction:

The demand for health professionals is unprecedentedly high globally. One response to this challenge has been expanding training through more liberal education policies, facilitating private sector participation in education service provision. Some evidence suggests that this is a double-edged sword, increasing quantity but compromising the quality of health professionals produced. Regulation can provide a framework to assure and continuously improve quality, with such regulation in place in 79% of World Health Organization African countries. However, it is unclear how much and what evidence has been generated on how accreditation happens, where it is concentrated, and the prevailing evidence gaps within this region; therefore, we propose to conduct a scoping review.

Inclusion criteria:

This review will include articles and dissertations focusing on the accreditation of health professionals’ education in Africa. All methodological approaches and designs will be included. Conference abstracts and protocols will be excluded.

Methods:

This review will be carried out according to the JBI scoping review methodology. We conducted an initial search of CINAHL and MEDLINE to identify relevant articles. This informed our selection of keywords, along with index terms, to create a comprehensive search strategy for CINAHL (EBSCOhost), MEDLINE (Ovid), Global Health (Ovid), ERIC (EBSCOhost), Web of Science Core Collection, Embase, and Scopus. Sources included will be limited to those published starting from 2000 onwards. Data will be presented using tables and charts, accompanied by a narrative summary.

Detail of this review project can be found in Open Science Framework:

https://doi.org/10.17605/OSF.IO/W5G7T
La obra común de la autoridad y de la libertad en la educación. Enseñanza de Lucien Laberthonnière y reflexiones críticas
Authors: Molteni Agostino , Solís-Nova David Alfonso
Published: October 2024

La evidencia histórica de los siglos pasados y actuales muestra los límites de una pretendida ciencia pedagógica y de sus métodos de aprendizaje concebidos a priori, es decir, entendidos como una teoría presupuesta. En este sentido, el método educativo propuesto por Lucien Laberthonnière (1860-1932) puede ser reconocido como un aporte notable y aún actual. Por ello, el objetivo de este estudio es, ante todo, presentar el pensamiento educativo de Laberthonnière. En segundo lugar, se quieren ofrecer algunas reflexiones críticas que prolonguen la lección del autor. Si para él la educación es una obra en común entre la autoridad del educador y la libertad del educando, ¿su fin es engendrar sujetos cívicos que estén habilitados para trabajar con el otro hombre, no contra él? En este sentido, se mostrará que su propuesta es la de una educación en la que el método de la relación compuesta entre la autoridad del educador y la libertad del educando sabe engendrar sujetos cívicos con miras a la producción de beneficios universales, es decir, civilizadores.
Playing with active matter
Authors: Barona Balda Angelo , Argun Aykut , Callegari Agnese , Volpe Giovanni
Published: October 2024

In the past 20 years, active matter has been a very successful research field, bridging the fundamental physics of nonequilibrium thermodynamics with applications in robotics, biology, and medicine. Active particles, contrary to Brownian particles, can harness energy to generate complex motions and emerging behaviors. Most active-matter experiments are performed with microscopic particles and require advanced microfabrication and microscopy techniques. Here, we propose some macroscopic experiments with active matter employing commercially available toy robots (the Hexbugs). We show how they can be easily modified to perform regular and chiral active Brownian motion and demonstrate through experiments fundamental signatures of active systems such as how energy and momentum are harvested from an active bath, how obstacles can sort active particles by chirality, and how active fluctuations induce attraction between planar objects (a Casimir-like effect). These demonstrations enable hands-on experimentation with active matter and showcase widely used analysis methods.
An instructional lab apparatus for quantum experiments with single nitrogen-vacancy centers in diamond
Authors: Yuan Zhiyang , Mukherjee Sounak , Thompson Jeff D. , de Leon Nathalie P. , Gardill Aedan , Kolkowitz Shimon
Published: October 2024

Hands-on experimental experience with quantum systems in the undergraduate physics curriculum provides students with a deeper understanding of quantum physics and equips them for the fast-growing quantum science industry. Here, we present an experimental apparatus for performing quantum experiments with single nitrogen-vacancy (NV) centers in diamond. This apparatus is capable of basic experiments such as single-qubit initialization, rotation, and measurement, as well as more advanced experiments investigating electron–nuclear spin interactions. We describe the basic physics of the NV center and give examples of potential experiments that can be performed with this apparatus. We also discuss the options and inherent trade-offs associated with the choice of diamond samples and hardware. The apparatus described here enables students to write their own experimental control and data analysis software from scratch, all within a single semester of a typical lab course, as well as to inspect the optical components and inner workings of the apparatus. We hope that this work can serve as a standalone resource for any institution that would like to integrate a quantum instructional lab into its undergraduate physics and engineering curriculum.
Acoustic encoding of vocally expressed confidence and doubt in Chinese bidialectics
Authors: Feng Shiyan , Jiang Xiaoming
Published: October 2024

Language communicators use acoustic-phonetic cues to convey a variety of social information in the spoken language, and the learning of a second language affects speech production in a social setting. It remains unclear how speaking different dialects could affect the acoustic metrics underlying the intended communicative meanings. Nine Chinese Bayannur-Mandarin bidialectics produced single-digit numbers in statements of both Standard Mandarin and the Bayannur dialect with different levels of intended confidence. Fifteen listeners judged the intention presence and confidence level. Prosodically unmarked and marked stimuli exhibited significant differences in perceived intention. A higher intended level was perceived as more confident. The acoustic analysis revealed the segmental (third and fourth formants, center of gravity), suprasegmental (mean fundamental frequency, fundamental frequency range, duration), and source features (harmonic to noise ratio, cepstral peak prominence) can distinguish between confident and doubtful expressions. Most features also distinguished between dialect and Mandarin productions. Interactions on fourth formant and mean fundamental frequency suggested that speakers made greater use of acoustic parameters to encode confidence and doubt in the Bayannur dialect than in Mandarin. In machine learning experiments, the above-chance-level overall classification rates for confidence and doubt and the in-group advantage supported the dialect theory.
Engineering supramolecular peptide nanofibers for in vivo platelet-hitchhiking beyond ligand-receptor recognition
Authors: Feng Yan , Liu Chenyang , Cui Weiping , Yang Liuqing , Wu Di , Zhang Hua , Wang Xueqing , Sun Yuqian , He Bing , Dai Wenbing , Zhang Qiang
Published: October 2024

Ex vivo or in vivo cell-hitchhiking has emerged as a potential means for efficient drug delivery and various disease therapies. However, many challenges remain, such as the complicated engineering process and dependence on ligand-receptor interaction. Here, we present a simple in vivo platelet-hitchhiking strategy based on self-assembling peptides without ligand modification. The engineered peptide nanofibers can hitchhike ultrafast (<5 s) and efficiently on both resting and activated platelets in a receptor-independent and species-independent manner. Mechanistic studies showed that unique secondary structure of nanofibers, which lead to surface exposure of hydrophobic and hydrogen bond–forming groups, might primarily contribute to the selective and efficient platelet-hitchhiking behavior. After intravenous injection, these peptide nanofibers hitchhiked in situ on circulating platelets and achieved almost 20-fold lung accumulation. Our study provides not only a different paradigm of in vivo platelet-hitchhiking beyond ligand-receptor recognition but also a potential strategy for lung-targeted drug delivery and pulmonary disease therapy.
The G
1
-S transition is promoted by Rb degradation via the E3 ligase UBR5
Authors: Zhang Shuyuan , Valenzuela Lucas Fuentes , Zatulovskiy Evgeny , Mangiante Lise , Curtis Christina , Skotheim Jan M.
Published: October 2024

Mammalian cells make the decision to divide at the G
1
-S transition in response to diverse signals impinging on the retinoblastoma protein Rb, a cell cycle inhibitor and tumor suppressor. Passage through the G
1
-S transition is initially driven by Rb inactivation via phosphorylation and by Rb’s decreasing concentration in G
1
. While many studies have identified the mechanisms of Rb phosphorylation, the mechanism underlying Rb’s decreasing concentration in G
1
was unknown. Here, we found that Rb’s concentration decrease in G
1
requires the E3 ubiquitin ligase UBR5.
UBR5
knockout cells have increased Rb concentration in early G
1
, exhibited a lower G
1
-S transition rate, and are more sensitive to inhibition of cyclin-dependent kinase 4/6 (Cdk4/6). This last observation suggests that UBR5 inhibition can strengthen the efficacy of Cdk4/6 inhibitor–based cancer therapies.
Transforming science labs into automated factories of discovery
Authors: Angelopoulos Angelos , Cahoon James F. , Alterovitz Ron
Published: October 2024

Laboratories in chemistry, biochemistry, and materials science are at the leading edge of technology, discovering molecules and materials to unlock capabilities in energy, catalysis, biotechnology, sustainability, electronics, and more. Yet, most modern laboratories resemble factories from generations past, with a large reliance on humans manually performing synthesis and characterization tasks. Robotics and automation can enable scientific experiments to be conducted faster, more safely, more accurately, and with greater reproducibility, allowing scientists to tackle large societal problems in domains such as health and energy on a shorter timescale. We define five levels of laboratory automation, from laboratory assistance to full automation. We also introduce robotics research challenges that arise when increasing levels of automation and when increasing the generality of tasks within the laboratory. Robots are poised to transform science labs into automated factories of discovery that accelerate scientific progress.
SARS-CoV-2 NSP6 reduces autophagosome size and affects viral replication via sigma-1 receptor
Authors: Zhang Cuiling , Jiang Qiwei , Liu Zirui , Li Nan , Hao Zhuo , Song Gaojie , Li Dapeng , Chen Minghua , Lin Lisen , Liu Yan , Li Xiao , Shang Chao , Li Yiquan
Published: October 2024

Autophagy is a cellular self-defense mechanism by which cells can kill invading pathogenic microorganisms and increase the presentation of components of pathogens as antigens. Contrarily, pathogens can utilize autophagy to enhance their own replication. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) NSP6 can interact with ATPase proton pump component to inhibit lysosomal acidification, which was implicated in the autophagy process. However, research on how SARS-CoV-2 NSP6 affected autophagy, and its impact on virus replication is still lacking. Coronavirus NSP6 has been reported to promote coronavirus replication by limiting autophagosome expansion. However, this finding has not been confirmed in coronavirus disease 2019 (COVID-19). We investigated the effect of NSP6 protein on autophagosomes in different mutant strains of SARS-CoV-2 and revealed that the size of autophagosomes was reduced by NSP6 of the wild-type and Delta variant of SARS-CoV-2. In addition, we found that SARS-CoV-2 NSP6 localized to the lysosome and had an inhibitory effect on the binding of autophagosomes to the lysosome, which blocked the autophagy flux; this may be related to endoplasmic reticulum (ER)-related pathways. We also found that sigma-1 receptor (SIGMAR1) knock out (KO) reversed NSP6-induced autophagosome abnormality and resisted SARS-CoV-2 infection, which responds to the fact that SIGMAR1 is likely to be used as a potential target for the treatment of SARS-CoV-2 infection. In summary, we have provided a preliminary explanation of the effects on autophagy of the SARS-CoV-2 NSP6 protein from the pre-autophagic and late stages, and also found that SIGMAR1 is likely to be used as a potential target for SARS-CoV-2 therapy to develop relevant drugs.

IMPORTANCE

We have provided a preliminary explanation of the effects on autophagy of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structure protein 6 from the pre-autophagic and late stages, and also found that sigma-1 receptor is likely to be used as a potential target for SARS-CoV-2 therapy to develop relevant drugs.
Conformational change as a mechanism for toxin activation in bacterial toxin-antitoxin systems
Authors: Sanchez-Torres Viviana , Hwang Hyeon-Ji , Wood Thomas K.
Published: October 2024

Toxin/antitoxin (TA) systems are present in nearly every prokaryotic genome and play the important physiological roles of phage inhibition by reducing metabolism (this includes persistence for the extreme case of complete cessation of metabolism), genetic element stabilization, and biofilm formation. TA systems have also been incorporated into other cell systems, such as CRISPR-Cas and phage quorum sensing. For the simplest and best-studied case, proteinaceous toxins and antitoxins (i.e., type II), toxin activity is masked by direct binding of the antitoxin. A long-standing, unresolved question in the TA field is how toxins are activated when bound to antitoxins at nanomolar affinity. The current paradigm envisions preferential degradation of the antitoxin by a protease, but this is highly unlikely in that a protease cannot discriminate between bound toxin and bound antitoxin because both are highly structured. Strikingly, recent results from several studies show one likely mechanism for toxin activation is conformational changes in the TA complex that result in the release or activation of the toxin as a result of a protein trigger, such as that from phages, and as a result of thermally-driven refolding dynamics.
Comparison of pathogenicity and host responses of emerging porcine reproductive and respiratory syndrome virus variants in piglets
Authors: Zhang Wenli , Wang Xinrong , Zhang He , Pan Yu , Ma Wenjie , Xu Yunfei , Tian Zhijun , Xia Changyou , Fu Lizhi , Wang Yue
Published: October 2024

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly variable virus with genetic diversity. This study comparatively examines the pathogenicity and immunological impact of two emergent PRRSV strains, SD53 and HuN4, in piglets. Our results indicate that SD53 strain induces milder clinical syndromes and less severe tissue damage than HuN4, despite similar replication rates. Hematological tests showed less perturbations in peripheral blood cell profiles after SD53 infection, suggesting a less systemic impact. The neutrophil-to-lymphocyte ratio was notably lower in SD53-infected piglets, suggesting a less intense inflammatory reaction. Moreover, SD53 infection led to lower levels of pro-inflammatory cytokines, further supporting a less pronounced inflammatory profile. Both strains induced the production of PRRSV-specific antibodies. However, transcriptomic analysis of lung and lymph node tissues from infected piglets disclosed a more moderate up-regulation of core genes, including
ISGs
, in the SD53 group. Further analysis indicated that SD53 primarily enhanced immune-related signaling, particularly in T cell response modules, while HuN4 caused a more robust pro-inflammatory reaction and a dampening of T cell functionality. Flow cytometry analyses confirmed these findings, showing higher CD4/CD8 ratios and increased CD4+ T cell percentages in SD53-infected piglets, implying a more robust T cell response. Collectively, these findings broaden our comprehension of PRRSV pathogenesis and may inform the development of future therapeutic or prophylactic strategies for controlling PRRSV infections more effectively.

IMPORTANCE

The high mutation rate of porcine reproductive and respiratory syndrome virus (PRRSV) poses significant challenges to its accurate diagnosis and the implementation of effective control measures. This research explores the pathogenic profiles of two emerging PRRSV stains: the NADC30-like strain SD53 and the highly pathogenic strain HuN4. Our investigation reveals that SD53 initiates distinct immunopathological responses
in vivo
compared with those provoked by HuN4. By conducting a transcriptome analysis of differential gene expression in the lungs and lymph nodes of infected piglets, we unveil the intricate molecular mechanisms underlying the contrasting pathogenicity of these two strains. The comprehensive insights yielded by this study are instrumental in advancing our understanding of the dominant NADC30-like PRRSV strain, which has become increasingly prevalent in China’s swine industry.
First dating of an early Chibanian (Middle Pleistocene) glacial overdeepening in the Alpine Foreland using the 4He/U-Th method
Authors: Tomonaga Yama , Buechi Marius W. , Deplazes Gaudenz , Kipfer Rolf
Published: October 2024

The 4He/U-Th dating method can be used to estimate the residence time of pore waters in low-permeable rocks and consolidated sediments, serving as a proxy for sediment deposition time. This residence time is inferred from the accumulation time of radiogenic 4He measured in the pore water being produced by the local decay of U and Th in the sediment matrix. We applied the 4He/U-Th method to date the pore waters of unconsolidated sediments from a glacial overdeepening in the Swiss Plateau (northern Alpine Foreland), where prior studies suggested sediments older than Marine Isotope Stage (MIS) 6 (191–130 ka). We show that compact and fine-grained (glaci)lacustrine sediments provide low-permeability conditions that allow 4He to accumulate in the pore water and be preserved in the pore space. The 4He/U-Th dating indicates that the sediments between 40 m and 140 m are 606 ± 122 ka. The dated infill was deposited in a glacial overdeepening eroded by a foreland glaciation larger than that of the Last Glacial Maximum (LGM). The results reveal extensive foreland glaciations and intense glacial overdeepening erosion during the early part of the Chibanian (i.e., Middle Pleistocene). This work highlights the potential of the 4He/U-Th method for dating sediments in similarly favorable hydrogeological settings.
The Cambrian of the Grand Canyon: Refinement of a Classic Stratigraphic Model
Authors: Dehler Carol , Sundberg Frederick , Karlstrom Karl , Crossey Laura , Schmitz Mark , Rowland Stephen , Hagadorn James
Published: October 2024

The Cambrian Tonto Group of the Grand Canyon was used by Edwin McKee in 1945 to make an insightful visual representation of how sedimentary facies record transgression across a craton—a common conceptual framework still used in geologic education. Although the tenets of McKee’s facies diagram persist, the integration of new stratigraphy, depositional models, paleontology, biostratigraphy, and other data is refining the underlying dynamics of this cratonic transgression. Instead of McKee’s interpretation of one major transgression with only minor regressions, there are at least five stratigraphic sequences, of which the lower three are separated by disconformities. These hiatal surfaces likely represent erosion of previously deposited Cambrian sediments that were laid down on the tropical, pre-vegetated landscape. Rather than being fully marine in origin, these sequences were formed by a mosaic of depositional environments including braided coastal plain, eolian, marginal marine, and various shallow marine environments. McKee, not having the insights of sequence stratigraphy and plate tectonics, concluded that the preservation of these sediments were due to predepositional topography and subsidence of the “geosyncline.” Our modern interpretation is that accommodation space was a result of eustasy and differential subsidence on the continental margin. Our modified depositional model provides a more effective teaching tool for fundamentals and nuances of modern stratigraphic thinking, using the Tonto Group as a still-influential type location for understanding transgressive successions.
VHLmissense mutation delineate aggressive clear cell renal cell carcinoma subtype with favorable immunotherapeutic response
Authors: Xu Ziyang , Liu Li , Jiang Wenbin , Qiu Youqi , Zhang Boyu , Cheng Jiangting , Luo Jiyan , Guo Jianming , Xu Jiejie
Published: October 2024

Background

von Hippel-Lindau (VHL) harbors the highest mutational frequency in clear cell renal cell carcinoma (ccRCC). AlthoughVHLmutational subtypes exert diverse impacts on the functionality of the VHL protein, the clinical significance ofVHLmutational heterogeneity remains largely obscure.

Methods

This study included a total of 1331 patients with ccRCC from localized data sets, including our localized Zhongshan Hospital (ZSHS) cohort (n=1270) and Zhongshan immune checkpoint blockade cohort (n=61), as well as 525 patients with ccRCC from two publicly available data sets with matched clinical annotation and multidimensional data. According to the putative biological effect, we subclassifiedVHLmutation intoVHLTruncandVHLMiss. The association ofVHLstatus with clinical outcomes, genomic, oncogenic and immunologic characteristics was further depicted.

Results

VHLMissccRCC was associated with reduced survival in the localized ZSHS and The Cancer Genome Atlas cohorts. Clinical benefit from immunotherapy was observed inVHLMisspatients in all immunotherapy cohorts.VHLMissccRCC exhibited hyper-activated cell cycle and nuclear factor kappa B (NF-κB) instead of canonical hypoxia inducible factor pathways, which might contribute to its proliferative morphology. Meanwhile,VHLMissccRCC featured an inflamed microenvironment with enriched tertiary lymphoid structures.

Conclusions

VHLMissmutations delineate an aggressive ccRCC subtype with distinct clinical outcomes, likely attributed to its specific oncogenic, morphologic and immunologic features.
Sustained drug-free remission in rheumatoid arthritis associated with diffuse large B-cell lymphoma following tandem CD20-CD19-directed non-cryopreserved CAR-T cell therapy using zamtocabtagene autoleucel
Authors: Szabo David , Balogh Alexandra , Gopcsa Laszlo , Giba-Kiss Laura , Lakatos Gergely , Paksi Melinda , Reti Marienn , Takacs Peter , Heteren Pearl van , Zadoyan Gregor , Holtkamp Silke , Overstijns Toon , Miltenyi Stefan , Remenyi Peter , Nagy György
Published: October 2024

We report the case of long-term persisting rheumatoid arthritis (RA), treated with CD20-CD19 CAR-T when it became associated with diffuse large B cell lymphoma (DLBCL), resulting in a sustained drug-free remission of the preceding RA, as well as of the subsequent DLBCL that formed the indication of the CAR-T therapy using zamtocabtagene autoleucel, with a 1-year follow-up. According to our best knowledge, this is the first published clinical case report of long-term persisting RA treated with CAR-T cell therapy.
Characterising the permanent deformation of subgrade soils under seasonal variation
Authors: Everton José H.C. , Erlingsson Sigurdur
Published: October 2024

Rutting, a prevalent failure mode in flexible pavements, largely stems from subgrade issues. Despite this, there is a lack of standard protocols to evaluate subgrade rutting or permanent deformation (PD). This study attempted to characterise PD in subgrades, focusing on a poorly graded sand and two silty sands. Moisture contents above and below optimum levels were considered to account for seasonal variations. The research involved adapting a test to assess the PD by determining typical stresses on the subgrade. Moreover, given these soils’ unsaturated state and medium- to fine-grained nature, suction is an important factor. Suction-controlled multi-stage repeated load triaxial tests were conducted, and the results were fitted by a PD model modified to account for suction. The characterisation was compared with the subgrade strain criterion used in pavement design solutions. Results indicated discrepancies between the PD characterisation and strain criteria predictions, with the silty sands performing better than the poorly graded sand, consistent with the shakedown theory.
Modern detector technologies of D-mesons identification for investigation of superdense nuclear matter
Authors: Zherebchevsky V. , Kondratiev V. , Maltsev N. , Petrov V.
Published: October 2024

In this work, new vertex detector for the precision registration of D mesons was proposed for MPD experiment at NICA collider. This conception includes three cylindrical inner layers of large area thin (40–50 [Formula: see text]m) silicon pixel sensors, bended around the collider beam pipe and located at a minimum distance from the interaction point of the beams. Also, detailed calculations of identification capability of this vertex detector, within the framework of the decays reconstruction of [Formula: see text] and D0 mesons formed in central Au-Au collisions at the NICA collider energies, have been done. Using these estimates of D mesons reconstruction efficiency, the yields of such mesons in MPD experiment were obtained.
The Impact of Learning, Fatigue, and Dependent Faults on Software Reliability
Authors: Samal Umashankar , Kumar Ajay
Published: October 2024

Software reliability is a critical factor in ensuring the quality and dependability of software systems. Historically, software errors were primarily attributed to coding mistakes. However, recent insights have revealed that human error is a dynamic phenomenon influenced by factors such as learning processes and fatigue. This paper presents an approach that incorporates tester fatigue into the debugging process, thereby improving the development of more realistic software reliability growth models (SRGMs). The proposed approach utilizes S-shaped learning curves and an exponential fatigue function to account for the dynamic nature of human error. Additionally, interdependencies between faults are considered in the analysis. The quality, predictive capabilities, and accuracy of the proposed models are rigorously evaluated using three well-established fit criteria: mean squared error (MSE), mean absolute error (MAE), and the coefficient of determination ([Formula: see text]), applied to two failure datasets. By integrating the fatigue factor into the proposed models, a more comprehensive representation of software reliability dynamics is provided. This research contributes to the advancement of software reliability analysis and enhances the assessment of software system dependability.
Optimal Proof-Testing Intervals with Functional Safety Constraint for E/E/PE Safety-Related Systems
Authors: Inoue Shinji , Fujiwara Takaji , Yamada Shigeru
Published: October 2024

Proof-testing for E/E/PE safety-related systems is known as a periodic inspection and maintenance activity to maintain their designed functional safety in operation. Generally, the proof-testing takes so much cost and time for checking the E/E/PE safety-related systems comprehensively. Therefore, effective proof-testing intervals should be considered based on the rationale for the hazardous risk and maintenance cost. As one of the approaches, there exist methods deriving economic proof-testing intervals minimizing simultaneous the proof-testing cost and the risk at hazardous event occurrence. However, the safety constraint should be needed to consider at the same time since the E/E/PE safety-related systems are required to maintain certain safety level in operation. This paper addresses a mathematical approach for obtaining optimal proof-testing intervals for such practical situations.
Mobile Phone Data Transforming Casework in Asylum Decision-making: Insights from the Danish Case
Authors: Nielsen Trine Rask , Gammeltoft-Hansen Thomas , Holten Møller Naja
Published: October 2024

The Danish Immigration Service estimates that approximately 20% of decisions in asylum cases are informed by data extracted from asylum seekers’ mobile phones, enabling more comprehensive constructions of data than passport or similar identification documents provide. Such data (e.g., from social media) feed into caseworker systems and inform decisions on whether to grant asylum to an applicant or not. During the asylum process both governmental authorities and non-governmental organizations (NGOs) have a formal role assisting individuals applying for asylum in understanding, intervening in, and participating in the socio-technical infrastructures through which data are produced and used, defined as data infrastructure literacy. In this article we ask: In the context of mobile phone data transforming asylum casework in Denmark, what characterizes data infrastructure literacy for different stakeholders in the asylum process, including those subjected to the asylum procedure? The research presented in this article is informed by qualitative data produced through semi-structured interviews (
N
= 10), summaries of asylum cases from both a public and a non-public dataset, and 160 hours of observational studies. Our findings suggest that data obtained from mobile phones have become an integral part of asylum decision-making. Furthermore, our findings suggest that data infrastructure literacy is conditioned by stakeholders’ understanding of mobile phone data as assembled and utilized in the following ways: (1) through distributed, collaborative, and data-driven efforts, (2) at every stage of the asylum procedure and beyond, (3) as back-up data for credibility assessment, (4) in unequal power dynamics of consent, and (5) by practices that continue to transform by use of new types of data. This is crucial for ensuring that individuals seeking asylum receive basic legal support during and after the implementation of new data infrastructures.
A Review on Blockchain Technology, Current Challenges, and AI-Driven Solutions
Authors: Abdelhamid Moetez , Sliman Layth , Ben Djemaa Raoudha , Perboli Guido
Published: October 2024

Blockchain provides several advantages, including decentralization, data integrity, traceability, and immutability. However, despite its advantages, blockchain suffers from significant limitations, including scalability, resource greediness, governance complexity, and some security related issues. These limitations prevent its adoption in mainstream applications. Artificial Intelligence (AI) can help addressing some of these limitations. This survey provides a detailed overview of the different blockchain AI-based optimization and improvement approaches, tools and methodologies proposed to meet the needs of existing systems and applications with their benefits and drawbacks. Afterward, the focus is on suggesting AI-based directions where to address some of the fundamental limitations of blockchain.
KNN-DBSCAN: a DBSCAN in high dimensions
Authors: Chen Youguang , Ruys William , Biros George
Published: October 2024

Clustering is a fundamental task in machine learning. One of the most successful and broadly used algorithms is DBSCAN, a density-based clustering algorithm. DBSCAN requires ϵ-nearest neighbor graphs of the input dataset, which are computed with range-search algorithms and spatial data structures like KD-trees. Despite many efforts to design scalable implementations for DBSCAN, existing work is limited to low-dimensional datasets, as constructing ϵ-nearest neighbor graphs can be expensive in high-dimensions. This article introduces a modified DBSCAN, using
k
-nearest neighbor (
k
NN) graphs to improve efficiency. We outline conditions for
k
NN-DBSCAN to match DBSCAN’s results and present a parallel implementation using OpenMP and MPI for shared and distributed memory systems. Testing on datasets up to 32 dimensions, we achieve remarkable scalability. Our implementation clusters one billion 3D points in under one second on 28K cores at TACC’s Frontera system. In a larger run, we cluster 65 billion points in 20 dimensions in under 40 seconds using 114,688 cores. Our method is up to 37× faster than state-of-the-art parallel DBSCAN on a 20-dimensional dataset with 4 million points. Code is available at
https://github.com/ut-padas/knndbscan
.
Sex Differences in Electrophysiology and Calcium Handling in Atrial Health and Fibrillation
Authors: Smith Charlotte E.R. , Ni Haibo , Grandi Eleonora
Published: October 2024

The importance of biological sex on disease etiology and outcomes has long been underinvestigated. While recent focus on characterizing sex differences in cardiac pathophysiology has led to improved inclusion of both sexes in scientific studies and clinical trials, much is still unknown about underlying differences in normal cardiac physiology. This is particularly true for the atria, where the most common arrhythmia, atrial fibrillation (AF), occurs. AF is associated with adverse structural, electrophysiological, and calcium handling remodeling that leads to patient morbidity and mortality. Differences in the onset, prevalence, presentation, and prognosis of AF are known to differ between males and females, yet the sex-specific baseline phenotypes from which AF arises are not well characterized. This review examines what is currently known about sex differences in atrial physiology, the alterations that occur in AF, potential mechanisms underlying sex divergence, and the need for sex-targeted therapeutic strategies.
Study of Electromagnetic Radiation From High‐Speed Train Voice and Data Antennae on the Health of Pacemaker Wearers
Authors: Tian Rui , Wu Hao , Lu Mai
Published: October 2024

In China, high‐speed trains have become a major means of transportation for the masses. When the passengers wearing pacemakers travel on high‐speed trains, electromagnetic environment in the carriage where the GSM‐R voice and data antennae are located should be concerned. In this work, a real‐size carriage monopole antennae simulating voice and data antennae as high‐frequency radiation sources and wearing pacemaker passenger’ models were established to study the electromagnetic exposure of the passenger at different conditions. The results showed that when the passenger faced the voice antenna, he suffered much greater electromagnetic radiation than when his back in turned from it. The electric field strength, average SAR, and temperature rise of the heart when facing the antenna were 27.3 V/m, 0.0102 W/kg, and 0.0016°C, respectively. Meanwhile, the temperature rise of the pacemaker was 0.001°C. We also obtained the values of electromagnetic dose for the whole body. All data were below the limits of the ICNIRP guidelines. These results indicate that the electromagnetic fields generated by the GSM‐R voice and data antennae do not harm the health of passengers wearing pacemaker.
Trace and Heavy Metals in Locally and Imported Spices Sold on Markets in Accra Metropolis, Ghana
Authors: Osei-Safo Isaac , Miezah Kodwo , Sackey Lyndon Nii Adjiri , Adusei-Gyamfi Junias , Abdul Ayamba Malik
Published: October 2024

Spices enhance food’s colour, aroma and palatability. The main objective of this study was to assess the levels of heavy metals in the most common spices used in Ghanaian and worldwide cuisines. Ninety samples were obtained directly from local marketplaces in the Accra Metropolis (Madina, Kaneshie and Makola). After microwave digestion, the samples’ levels of arsenic, iron, lead, cadmium and zinc were measured using an inductively coupled plasma‐mass spectrometer (ICP‐MS). Iron, zinc, arsenic, cadmium and lead levels in specified natural spices varied from 0.022 mg/kg to 5.814 mg/kg, 0.056 mg/kg to 0.895 mg/kg, not detected to 14.012 mg/kg, 0.02 mg/kg to 0.45 mg/kg and not detected to 3.583 mg/kg, respectively. The toxic metals arsenic and lead in turmeric powder, whole rosemary and garlic, as well as lead in ginger, were slightly above the Codex, but below the FAO/WHO permissible level. All spices in this study had THQ and HI values of less than one, indicating that consumers will experience no potential health hazards from consuming specific metals through spices. However, continual scrutiny should be maintained over time due to bioaccumulation in humans.
Genetic Variations in AMPK, FOXO3A, and POMC Increase the Risk of Extreme Obesity
Authors: Santana Cinthia Vila Nova , Magno Luiz Alexandre Viana , Ramos Adauto Versiani , Rios Maria Angélica , Sandrim Valéria Cristina , De Marco Luiz Armando , Miranda Débora Marques de , Romano-Silva Marco Aurélio
Published: October 2024

Objective: Genetic variability significantly impacts metabolism, weight gain, and feeding behaviors, predisposing individuals to obesity. This study explored how variations in key genes related to obesity—FOXO3A (forkhead box O3), AMPK (protein kinase AMP‐activated), and POMC (proopiomelanocortin)—are associated with extreme obesity (EOB).

Methods: We conducted a case–control study with 251 EOB patients and 212 healthy controls with a body mass index (BMI) of less than 25 kg/m2. We genotyped 10 single nucleotide variants (SNVs) using TaqMan‐based assays.

Results: Four SNVs—rs1536057 in FOXO3A, rs103685 in AMPK, rs934778, and rs6545975 in POMC—were associated with an increased risk of EOB. The strongest association was observed with rs934778 (POMC), which had a maximum odds ratio (OR) of 5.26 (95% CI: 2.86–9.09). While these genetic variations are closely linked to EOB, they do not affect serum glucose, triglycerides, HDL, LDL, BMI, or waist circumference.

Conclusions: These findings indicate that factors beyond traditional metabolic pathways, potentially related to feeding behavior or hormonal regulation, may also link these genetic variations to obesity. Further research in a larger sample is essential to validate these findings and explore their potential to guide clinical interventions and public health strategies.
Microarray Analysis of Visceral Adipose Tissue in Obese Women Reveals Common Crossroads Among Inflammation, Metabolism, Addictive Behaviors, and Cancer
Authors: Martínez-Romero Rolando , González-Chávez Susana Aideé , Urías-Rubí Victor Roberto , Gómez-Moreno Víctor Manuel , Blanco-Cantero Manlio Favio , Bernal-Velázquez Héctor Mario , Luévano-González Arturo , Pacheco-Tena César
Published: October 2024

Background: Visceral adipose tissue (VAT) abnormalities are directly associated with obesity‐associated disorders. The underlying mechanisms that confer increased pathological risk to VAT in obesity have not been fully described.

Methods: A case‐control study was conducted that included 10 women with obesity (36.80 ± 7.39 years, BMI ≥ 30 kg/m2) and 10 women of normal weight (32.70 ± 9.45 years, BMI < 24.9 kg/m2). RNA was extracted from greater omentum biopsies, and, using a DNA microarray, differential transcriptomic expression of VAT in women with obesity was evaluated taking as a reference that of women with normal weight. The differentially expressed genes (DEGs) were classified into functional biological processes and signaling pathways; moreover, the protein–protein interaction (PPI) networks were integrated for a deeper analysis of the pathways and genes involved in the central obesity‐associated disorders. The expression of TNF‐α, MAPK, and AKT proteins was also quantified in VAT.

Results: The VAT of women with obesity had 3808 DEGs, mainly associated with the cellular process of inflammation and carbohydrates and lipid metabolism. Overexpressed genes were associated with inflammatory, metabolic, hormonal, neuroendocrine, carcinogenic, and infectious pathways. Cellular processes related to addictive behaviors were notable. MAPK and PI3K‐AKT pathways were overexpressed, and Mapk1 and Akt3 genes were common crossing points among obesity‐associated disorders’ pathways. The increased expression of MAPK, AKT, and TNF proteins was confirmed in the VAT of women with obesity.

Conclusion: VAT confers a complex and blended pathogenic transcriptomic profile in obese patients, where abnormal processes are mainly controlled by activating intracellular signaling pathways that exhibit a high degree of redundancy. Identifying shared cross points between those pathways could allow specific targeting treatments to exert a widespread effect over multiple pathogenic processes.