bluuebunny/crossref_metadata_2025 huggingface dataset:
Zum Potenzial der digitalen Erfassung zur Analyse der Schreibmotorik
Authors: Marquardt Christian
Published: March 2024

Zusammenfassung: Hintergrund: Die seit langem diskutierten gravierenden Schreibprobleme von Kindern in der Schule scheinen sich in neuerer Zeit sogar zu verschärfen. Die Kinder schreiben zu langsam, verwenden einen erhöhten Schreibdruck, haben eine schlechte Schreibhaltung und ermüden rasch. Bei einer bundesweiten Umfrage des Schreibmotorik Instituts zusammen mit dem deutschen Lehrerverband (2019) an mehr als 2.000 Grundschulen und weiterführenden Schulen in Deutschland (Wiederholung 2022 bei 841 Befragten) gaben die befragten Lehrer an, dass 32% (2022: 30%) der Mädchen und sogar 51% (2022: 51%) der Jungen Probleme mit der Entwicklung einer lesbaren und flüssigen Handschrift haben. Fast zwei Drittel könnten nicht länger als 30 Minuten beschwerdefrei schreiben. Als Ursache wurde vor allem ein Mangel an motorischen Kompetenzen genannt. Diskussion: In der Regel reichen Schriftproben auf Papier oder die direkte Beobachtung der Schreibbewegung nicht aus, um Probleme der Schreibmotorik korrekt zu erfassen. Die Beurteilung von Schreibbewegungen, auch bei langsameren Schreibbewegungen, ist stark eingeschränkt, weil das Auge schnelleren Wechselbewegungen nicht folgen kann. Bis heute stehen für die Diagnostik von Schreibproblemen keine allgemein akzeptierten Beobachtungskriterien zur Verfügung. Zur objektiven Analyse von Schreibbewegungen stehen aber technische Registrierungssysteme zur Verfügung, die konsequenter eingesetzt werden sollten.
Sex differences in adipose insulin resistance are linked to obesity, lipolysis and insulin receptor substrate 1
Authors: Arner Peter , Viguerie Nathalie , Massier Lucas , Rydén Mikael , Astrup Arne , Blaak Ellen , Langin Dominique , Andersson Daniel Peter
Published: March 2024

Background/Objective

Insulin resistance is more prominent in men than women. If this involves adipose tissue is unknown and was presently examined.

Subjects/Methods

AdipoIR (in vivo adipose insulin resistance index) was measured in 2344 women and 787 men. In 259 of the women and 54 of the men, insulin induced inhibition of lipolysis (acylglycerol breakdown) and stimulation of lipogenesis (glucose conversion to acylglycerols) were determined in subcutaneous adipocytes; in addition, basal (spontaneous) lipolysis was also determined in the fat cells. In 234 women and 115 men, RNAseq expression of canonical insulin signal genes were measured in subcutaneous adipose tissue. Messenger RNA transcripts of the most discriminant genes were quantified in 175 women and 109 men.

Results

Men had higher AdipoIR values than women but only when obesity (body mass index 30 kg/m2 or more) was present (p < 0.0001). The latter sex dimorphism was found among physically active and sedentary people, in those with and without cardiometabolic disease and in people using nicotine or not (p = 0.0003 or less). In obesity, adipocyte insulin sensitivity (half maximum effective hormone concentration) and maximal antilipolytic effect were tenfold and 10% lower, respectively, in men than women (p = 0.005 or less). Basal rate of lipolysis was two times higher in men than women (p > 0.0001). Sensitivity and maximum effect of insulin on lipogenesis were similar in both sexes (p = 0.26 and p = 0.18, respectively). When corrected for multiple comparison only RNAseq expression of insulin receptor substrate 1 (IRS1) was lower in men than women (p < 0.0001). The mRNA transcript for IRS1 was 60% higher in women than men (p < 0.0001).

Conclusions

In obesity, adipose tissue insulin resistance is more pronounced in men than in women. The mechanism involves less efficient insulin-mediated inhibition of adipocyte lipolysis, increased basal rate of lipolysis and decreased adipose expression of a key element of insulin signaling, IRS1.
Differential in vivo roles of Mpl cytoplasmic tyrosine residues in murine hematopoiesis and myeloproliferative disease
Authors: Behrens Kira , Kauppi Maria , Viney Elizabeth M. , Kueh Andrew J. , Hyland Craig D. , Willson Tracy A. , Salleh Liam , de Graaf Carolyn A. , Babon Jeffrey J. , Herold Marco J. , Nicola Nicos A. , Alexander Warren S.
Published: March 2024

Thrombopoietin (Tpo), which binds to its specific receptor, the Mpl protein, is the major cytokine regulator of megakaryopoiesis and circulating platelet number. Tpo binding to Mpl triggers activation of Janus kinase 2 (Jak2) and phosphorylation of the receptor, as well as activation of several intracellular signalling cascades that mediate cellular responses. Three tyrosine (Y) residues in the C-terminal region of the Mpl intracellular domain have been implicated as sites of phosphorylation required for regulation of major Tpo-stimulated signalling pathways: Mpl-Y565, Mpl-Y599 and Mpl-Y604. Here, we have introduced mutations in the mouse germline and report a consistent physiological requirement for Mpl-Y599, mutation of which resulted in thrombocytopenia, deficient megakaryopoiesis, low hematopoietic stem cell (HSC) number and function, and attenuated responses to myelosuppression. We further show that in models of myeloproliferative neoplasms (MPN), where Mpl is required for pathogenesis, thrombocytosis was dependent on intact Mpl-Y599. In contrast, Mpl-Y565 was required for negative regulation of Tpo responses; mutation of this residue resulted in excess megakaryopoiesis at steady-state and in response to myelosuppression, and exacerbated thrombocytosis associated with MPN.
A review of real-world evidence on preemptive pharmacogenomic testing for preventing adverse drug reactions: a reality for future health care
Authors: Chenchula Santenna , Atal Shubham , Uppugunduri Chakradhara Rao S
Published: March 2024

Adverse drug reactions (ADRs) are a significant public health concern and a leading cause of hospitalization; they are estimated to be the fourth leading cause of death and increasing healthcare costs worldwide. Carrying a genetic variant could alter the efficacy and increase the risk of ADRs associated with a drug in a target population for commonly prescribed drugs. The use of pre-emptive pharmacogenetic/omic (PGx) testing can improve drug therapeutic efficacy, safety, and compliance by guiding the selection of drugs and/or dosages. In the present narrative review, we examined the current evidence of pre-emptive PGx testing-based treatment for the prevention of ADRs incidence and hospitalization or emergency department visits due to serious ADRs, thus improving patient safety. We then shared our perspective on the importance of preemptive PGx testing in clinical practice for the safe use of medicines and decreasing healthcare costs.
Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans
Authors: Fan Lin , Liu Junwei , Hu Wei , Chen Zexin , Lan Jie , Zhang Tongtong , Zhang Yang , Wu Xianpeng , Zhong Zhiwei , Zhang Danyang , Zhang Jinlong , Qin Rui , Chen Hui , Zong Yunfeng , Zhang Jianmin , Chen Bing , Jiang Jun , Cheng Jifang , Zhou Jingyi , Gao Zhiwei , Liu Zhenjie , Chai Ying , Fan Junqiang , Wu Pin , Chen Yinxuan , Zhu Yuefeng , Wang Kai , Yuan Ying , Huang Pintong , Zhang Ying , Feng Huiqin , Song Kaichen , Zeng Xun , Zhu Wei , Hu Xinyang , Yin Weiwei , Chen Wei , Wang Jian’an
Published: March 2024

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without FcγR-binding capability. Our analysis shows that anti-PD-1 mAb with FcγR-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without FcγR-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.
Early exposure to sugar sweetened beverages or fruit juice differentially influences adult adiposity
Authors: Benton David , Young Hayley A.
Published: March 2024

Objective

To examine associations between different types of sweet drinks consumed in early life and adult adiposity.

Design

The analysis involved the secondary analysis of the Avon Longitudinal Study of Parents and Children which followed children from birth to 24 years. Adiposity was measured using Dual-energy X-ray absorptiometry while food frequency questionnaires and diaries monitored diet. ‘Early exposure’ to sweet drinks was defined as giving a sugar-sweetened beverage or 100% fruit juice (FJ), before two years of age.

Results

Early exposure to cola was associated with higher fat mass, android fat mass and BMI at age 24 years; whereas early exposure to apple juice was associated with lower adult adiposity in females but not males. When age three, exposure to cola was associated with a greater intake of energy, carbohydrates, protein, fat, and less fruit and more fried foods. In contrast, early exposure to apple juice was associated with higher protein and lower fat intakes and consuming more fruits/vegetables and less fried foods. Parental education, adiposity and socio-economic status influenced whether SSB or FJ was given to a child.

Conclusions

Early drinking of sugar sweetened beverages was associated with a less healthy dietary pattern, and greater adult adiposity. Early drinking of apple juice was associated with a healthier dietary pattern, and lower fat mass in adult females. The choice of drink was associated with social deprivation. As the dietary causes of adult obesity begin in early childhood, increased attention should be given to diet in the first years of life.
Biobased and biodegradable films exhibiting circularly polarized room temperature phosphorescence
Authors: Cao Mengnan , Ren Yiran , Wu Yue , Shen Jingjie , Li Shujun , Yu Zhen-Qiang , Liu Shouxin , Li Jian , Rojas Orlando J. , Chen Zhijun
Published: March 2024

There is interest in developing sustainable materials displaying circularly polarized room-temperature phosphorescence, which have been scarcely reported. Here, we introduce biobased thin films exhibiting circularly polarized luminescence with simultaneous room-temperature phosphorescence. For this purpose, phosphorescence-active lignosulfonate biomolecules are co-assembled with cellulose nanocrystals in a chiral construct. The lignosulfonate is shown to capture the chirality generated by cellulose nanocrystals within the films, emitting circularly polarized phosphorescence with a 0.21 dissymmetry factor and 103 ms phosphorescence lifetime. By contrast with most organic phosphorescence materials, this chiral-phosphorescent system possesses phosphorescence stability, with no significant recession under extreme chemical environments. Meanwhile, the luminescent films resist water and humid environments but are fully biodegradable (16 days) in soil conditions. The introduced bio-based, environmentally-friendly circularly polarized phosphorescence system is expected to open many opportunities, as demonstrated here for information processing and anti-counterfeiting.
Advancing the scale of synthetic biology via cross-species transfer of cellular functions enabled by iModulon engraftment
Authors: Choe Donghui , Olson Connor A. , Szubin Richard , Yang Hannah , Sung Jaemin , Feist Adam M. , Palsson Bernhard O.
Published: March 2024

Machine learning applied to large compendia of transcriptomic data has enabled the decomposition of bacterial transcriptomes to identify independently modulated sets of genes, such iModulons represent specific cellular functions. The identification of iModulons enables accurate identification of genes necessary and sufficient for cross-species transfer of cellular functions. We demonstrate cross-species transfer of: 1) the biotransformation of vanillate to protocatechuate, 2) a malonate catabolic pathway, 3) a catabolic pathway for 2,3-butanediol, and 4) an antimicrobial resistance to ampicillin found in multiple Pseudomonas species to Escherichia coli. iModulon-based engineering is a transformative strategy as it includes all genes comprising the transferred cellular function, including genes without functional annotation. Adaptive laboratory evolution was deployed to optimize the cellular function transferred, revealing mutations in the host. Combining big data analytics and laboratory evolution thus enhances the level of understanding of systems biology, and synthetic biology for strain design and development.
Dislocation Majorana bound states in iron-based superconductors
Authors: Hu Lun-Hui , Zhang Rui-Xing
Published: March 2024

We show that lattice dislocations of topological iron-based superconductors such as FeTe1−xSex will intrinsically trap non-Abelian Majorana quasiparticles, in the absence of any external magnetic field. Our theory is motivated by the recent experimental observations of normal-state weak topology and surface magnetism that coexist with superconductivity in FeTe1−xSex, the combination of which naturally achieves an emergent second-order topological superconductivity in a two-dimensional subsystem spanned by screw or edge dislocations. This exemplifies a new embedded higher-order topological phase in class D, where Majorana zero modes appear around the “corners” of a low-dimensional embedded subsystem, instead of those of the full crystal. A nested domain wall theory is developed to understand the origin of these defect Majorana zero modes. When the surface magnetism is absent, we further find that s± pairing symmetry itself is capable of inducing a different type of class-DIII embedded higher-order topology with defect-bound Majorana Kramers pairs. We also provide detailed discussions on the real-world material candidates for our proposals, including FeTe1−xSex, LiFeAs, β-PdBi2, and heterostructures of bismuth, etc. Our work establishes lattice defects as a new venue to achieve high-temperature topological quantum information processing.
Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation
Authors: Karim Farina , Riou Catherine , Bernstein Mallory , Jule Zesuliwe , Lustig Gila , van Graan Strauss , Keeton Roanne S. , Upton Janine-Lee , Ganga Yashica , Khan Khadija , Reedoy Kajal , Mazibuko Matilda , Govender Katya , Thambu Kershnee , Ngcobo Nokuthula , Venter Elizabeth , Makhado Zanele , Hanekom Willem , von Gottberg Anne , Hoque Monjurul , Karim Quarraisha Abdool , Abdool Karim Salim S. , Manickchund Nithendra , Magula Nombulelo , Gosnell Bernadett I. , Lessells Richard J. , Moore Penny L. , Burgers Wendy A. , de Oliveira Tulio , Moosa Mahomed-Yunus S. , Sigal Alex
Published: March 2024

SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants.
Imprint of urbanization on snow precipitation over the continental USA
Authors: Salvi Kaustubh Anil , Kumar Mukesh
Published: March 2024

Urbanization can alter the local climate through modifications in land-atmosphere feedback. However, a continental scale evaluation of its influence on precipitation phase remains unknown. Here, we assess the difference in the likelihood of snow dominated events (SDEs) over 7,415 urban and surrounding non-urban (buffer) regions across the continental United States. Among 4,856 urban-buffer pairs that received at least five SDEs per year, 81% of urban regions are characterized by a smaller snow probability, 99% by a lower frequency of SDEs, and 57% by faster declining trends in SDEs compared to their buffer counterparts. Notably, urban (buffer) regions with lower snow probability are often characterized by higher net incoming and sensible energy fluxes as compared to buffer (urban) regions, thus highlighting the influence of land-energy feedback on precipitation phase. Results highlight a clear imprint of urbanization on precipitation phase and underscore the need to consider these influences while projecting hydro-meteorological risks.
Bubble-water/catalyst triphase interface microenvironment accelerates photocatalytic OER via optimizing semi-hydrophobic OH radical
Authors: Ren Guanhua , Zhou Min , Hu Peijun , Chen Jian-Fu , Wang Haifeng
Published: March 2024

Photocatalytic water splitting (PWS) as the holy grail reaction for solar-to-chemical energy conversion is challenged by sluggish oxygen evolution reaction (OER) at water/catalyst interface. Experimental evidence interestingly shows that temperature can significantly accelerate OER, but the atomic-level mechanism remains elusive in both experiment and theory. In contrast to the traditional Arrhenius-type temperature dependence, we quantitatively prove for the first time that the temperature-induced interface microenvironment variation, particularly the formation of bubble-water/TiO2(110) triphase interface, has a drastic influence on optimizing the OER kinetics. We demonstrate that liquid-vapor coexistence state creates a disordered and loose hydrogen-bond network while preserving the proton transfer channel, which greatly facilitates the formation of semi-hydrophobic •OH radical and O-O coupling, thereby accelerating OER. Furthermore, we propose that adding a hydrophobic substance onto TiO2(110) can manipulate the local microenvironment to enhance OER without additional thermal energy input. This result could open new possibilities for PWS catalyst design.
CRISPR-powered quantitative keyword search engine in DNA data storage
Authors: Zhang Jiongyu , Hou Chengyu , Liu Changchun
Published: March 2024

Despite the growing interest of archiving information in synthetic DNA to confront data explosion, quantitatively querying the data stored in DNA is still a challenge. Herein, we present Search Enabled by Enzymatic Keyword Recognition (SEEKER), which utilizes CRISPR-Cas12a to rapidly generate visible fluorescence when a DNA target corresponding to the keyword of interest is present. SEEKER achieves quantitative text searching since the growth rate of fluorescence intensity is proportional to keyword frequency. Compatible with SEEKER, we develop non-collision grouping coding, which reduces the size of dictionary and enables lossless compression without disrupting the original order of texts. Using four queries, we correctly identify keywords in 40 files with a background of ~8000 irrelevant terms. Parallel searching with SEEKER can be performed on a 3D-printed microfluidic chip. Overall, SEEKER provides a quantitative approach to conducting parallel searching over the complete content stored in DNA with simple implementation and rapid result generation.
Unconventional superconductivity near a nematic instability in a multi-orbital system
Authors: Islam Kazi Ranjibul , Chubukov Andrey
Published: March 2024

We analyze superconductivity in a multi-orbital fermionic system near the onset of a nematic order, using doped FeSe as an example. We associate nematicity with spontaneous polarization between dxz and dyz orbitals. We derive pairing interaction, mediated by soft nematic fluctuations, and show that it is attractive, and its strength depends on the position on the Fermi surface. As the consequence, right at the nematic quantum-critical point (QCP), superconducting gap opens up at Tc only at special points and extends into finite arcs at T < Tc. In between the arcs the Fermi surface remains intact. This leads to highly unconventional behavior of the specific heat, with no jump at Tc and seemingly finite offset at T = 0. We discuss gap structure and pairing symmetry away from a QCP and compare nematic and spin-fluctuation scenarios. We apply the results to FeSe1−xSx and FeSe1−xTex.
Test for BCS-BEC crossover in the cuprate superconductors
Authors: Chen Qijin , Wang Zhiqiang , Boyack Rufus , Levin K.
Published: March 2024

In this paper we address the question of whether high-temperature superconductors have anything in common with BCS-BEC crossover theory. Towards this goal, we present a proposal and related predictions which provide a concrete test for the applicability of this theoretical framework. These predictions characterize the behavior of the Ginzburg-Landau coherence length, $${\xi }_{0}^{{{{\rm{coh}}}}}$$

ξ

0

coh

, near the transition temperature Tc, and across the entire superconducting Tc dome in the phase diagram. That we are lacking a systematic characterization of $${\xi }_{0}^{{{{\rm{coh}}}}}$$

ξ

0

coh

in the entire class of cuprate superconductors is perhaps surprising, as it is one of the most fundamental properties of any superconductor. This paper is written to motivate further experiments and, thus, address this shortcoming. Here we show how measurements of $${\xi }_{0}^{{{{\rm{coh}}}}}$$

ξ

0

coh

contain direct indications for whether or not the cuprates are associated with BCS-BEC crossover and, if so, where within the crossover spectrum a particular superconductor lies.
Genome assemblies of 11 bamboo species highlight diversification induced by dynamic subgenome dominance
Authors: Ma Peng-Fei , Liu Yun-Long , Guo Cen , Jin Guihua , Guo Zhen-Hua , Mao Ling , Yang Yi-Zhou , Niu Liang-Zhong , Wang Yu-Jiao , Clark Lynn G. , Kellogg Elizabeth A. , Xu Zu-Chang , Ye Xia-Ying , Liu Jing-Xia , Zhou Meng-Yuan , Luo Yan , Yang Yang , Soltis Douglas E. , Bennetzen Jeffrey L. , Soltis Pamela S. , Li De-Zhu
Published: March 2024

Polyploidy (genome duplication) is a pivotal force in evolution. However, the interactions between parental genomes in a polyploid nucleus, frequently involving subgenome dominance, are poorly understood. Here we showcase analyses of a bamboo system (Poaceae: Bambusoideae) comprising a series of lineages from diploid (herbaceous) to tetraploid and hexaploid (woody), with 11 chromosome-level de novo genome assemblies and 476 transcriptome samples. We find that woody bamboo subgenomes exhibit stunning karyotype stability, with parallel subgenome dominance in the two tetraploid clades and a gradual shift of dominance in the hexaploid clade. Allopolyploidization and subgenome dominance have shaped the evolution of tree-like lignified culms, rapid growth and synchronous flowering characteristic of woody bamboos as large grasses. Our work provides insights into genome dominance in a remarkable polyploid system, including its dependence on genomic context and its ability to switch which subgenomes are dominant over evolutionary time.
Prevalence, outcomes and associated factors of SARS-CoV-2 infection in psoriasis patients of Southwest China: a cross-sectional survey
Authors: Zou Yang , Xu Jing , Chen Ai-Jun , Huang Kun , Zhu Shou-Min , Li Jian-Jun , He Jin , Li Jun-Zhi , Xiong Jian-Xia , Fan Yu-Kun , Liu Chuan , Pan Yun , Wang Ping
Published: March 2024

In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine’s effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.
Statistical detection of selfish mining in proof-of-work blockchain systems
Authors: Li Sheng-Nan , Campajola Carlo , Tessone Claudio J.
Published: March 2024

The core of many cryptocurrencies is the decentralised validation network operating on proof-of-work technology. In these systems, validation is done by so-called miners who can digitally sign blocks once they solve a computationally-hard problem. Conventional wisdom generally considers this protocol as secure and stable as miners are incentivised to follow the behaviour of the majority. However, whether some strategic mining behaviours occur in practice is still a major concern. In this paper we target this question by focusing on a security threat: a selfish mining attack in which malicious miners deviate from protocol by not immediately revealing their newly mined blocks. We propose a statistical test to analyse each miner’s behaviour in five popular cryptocurrencies: Bitcoin, Litecoin, Monacoin, Ethereum and Bitcoin Cash. Our method is based on the realisation that selfish mining behaviour will cause identifiable anomalies in the statistics of miner’s successive blocks discovery. Secondly, we apply heuristics-based address clustering to improve the detectability of this kind of behaviour. We find a marked presence of abnormal miners in Monacoin and Bitcoin Cash, and, to a lesser extent, in Ethereum. Finally, we extend our method to detect coordinated selfish mining attacks, finding mining cartels in Monacoin where miners might secretly share information about newly mined blocks in advance. Our analysis contributes to the research on security in cryptocurrency systems by providing the first empirical evidence that the aforementioned strategic mining behaviours do take place in practice.
A novel trauma induced urethral stricture in rat model
Authors: Wu Ziqiang , Tang Zhengyan , Zheng Zhihuan , Tan Shuo
Published: March 2024

Urethral stricture (US) is a longstanding disease, while there has not existed a suitable animal model to mimic the condition. We aimed to establish a trauma-induced US animal model to simulate this clinical scenario. A total of 30 rats were equally distributed into two groups, sham and US group. All rats were anesthetized with isoflurane and undergone cystostomy. In the US group, a 2 mm incision was made in the urethra and sutured to induce US. The sham group only make a skin incision on the ventral side of the anterior urethra. 4 weeks later, ultrasound and cystourethrography were performed to evaluate the degree of urethral stricture, pathological examinations were carried out to evaluate the degree of fibrosis. Urodynamic evaluation and mechanical tissue testing were performed to evaluate the bladder function and urethral tissue stiffness. The results showed that the urethral mucosa was disrupted and urethral lumen was stenosed in the US group. Additionally, the US group showed elevated bladder pressure, prolonged micturition intervals and increased tissue stiffness. In conclusion, the rat urethral stricture model induced by trauma provides a closer representation of the real clinical scenario. This model will significantly contribute to advancing research on the mechanisms underlying traumatic urethral stricture.
Impact of LKB1 status on radiation outcome in patients with stage III non-small-cell lung cancer
Authors: Sitthideatphaiboon Piyada , Nantavithya Chonnipa , Chantranuwat Poonchavist , Vinayanuwattikun Chanida , Sriuranpong Virote
Published: March 2024

Preclinical studies suggest that loss of LKB1 expression renders cancer cells less responsive to radiation partly through NRF2-mediated upregulation of antioxidant enzymes protecting against radiation-induced DNA damage. Here we investigated the association of an alteration in this pathway with radio-resistance in lung cancer patients. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) who were treated with chemoradiotherapy (CRT) and analyzed for LKB1 expression using semiquantitative immunohistochemistry. Clinical characteristics and expression of LKB1 were analyzed for association with radiotherapy outcomes. We analyzed 74 available tumor specimens from 178 patients. After a median follow-up of 40.7 months, 2-year cumulative incidence of locoregional recurrence (LRR) in patients who had LKB1Low expression was significantly higher than those with LKB1High expression (68.8% vs. 31.3%, P = 0.0001). LKB1Low expression was found significantly associated with a higher incidence of distant metastases (DM) (P = 0.0008), shorter disease-free survival (DFS) (P = 0.006), and worse overall survival (OS) (P = 0.02) compared to LKB1High expression. Moreover, patients with LKB1Low expression showed a significantly higher 2-year cumulative incidence of LRR (77.6% vs. 21%; P = 0.02), higher DM recurrence (P = 0.002), and shorter OS (P < 0.0001) compared with the EGFR-mutant group. For all patients with LKB1Low who had LRR, these recurrences occurred within the field of radiation, in contrast to those with LKB1High expression having both in-field, marginal, and out-of-field failures. LKB1 expression may serve as a potential biomarker for poor outcomes after receiving radiation in LA-NSCLC patients. Further studies to confirm the association and application are warranted.
Microfluidic production of amiodarone loaded nanoparticles and application in drug repositioning in ovarian cancer
Authors: Saorin Asia , Saorin Gloria , Duzagac Fahriye , Parisse Pietro , Cao Ni , Corona Giuseppe , Cavarzerani Enrico , Rizzolio Flavio
Published: March 2024

Amiodarone repositioning in cancer treatment is promising, however toxicity limits seem to arise, constraining its exploitability. Notably, amiodarone has been investigated for the treatment of ovarian cancer, a tumour known for metastasizing within the peritoneal cavity. This is associated with an increase of fatty acid oxidation, which strongly depends on CPT1A, a transport protein which has been found overexpressed in ovarian cancer. Amiodarone is an inhibitor of CPT1A but its role still has to be explored. Therefore, in the present study, amiodarone was tested on ovarian cancer cell lines with a focus on lipid alteration, confirming its activity. Moreover, considering that drug delivery systems could lower drug side effects, microfluidics was employed for the development of drug delivery systems of amiodarone obtaining simultaneously liposomes with a high payload and amiodarone particles. Prior to amiodarone loading, microfluidics production was optimized in term of temperature and flow rate ratio. Moreover, stability over time of particles was evaluated. In vitro tests confirmed the efficacy of the drug delivery systems.
Improving hand hygiene of young children with a digital intervention: a cluster-randomised controlled field trial
Authors: Graichen Joanna , Stingl Carlo , Pakarinen Anni , Rosio Riitta , Terho Kirsi , Günther Sebastian A. , Salanterä Sanna , Staake Thorsten
Published: March 2024

Contagious diseases that affect young children place a great burden on them and their families. Proper hand hygiene is an important measure to reduce the disease burden, however, its implementation in day care centres is challenging. This paper introduces a digital intervention to support independent and good handwashing among young children. The intervention leverages animated instructions triggered by water and soap use, together with a symbolic reward shown to children on a screen during and immediately after handwashing. We tested the intervention in a pre-registered, cluster-randomised controlled field trial in 4 day care centres in Finland and Germany with 162 children over 42 days. The intervention increased soaping time, used as a proxy for handwashing quality, by 5.30 s (+ 62%, p < 0.001). The effect occurs immediately at the onset of the intervention and is maintained throughout the intervention phase.
The study on the appearance of deformation defects in the yacht lamination process using an AI algorithm and expert knowledge
Authors: Szalewski Paweł , Niksa-Rynkiewicz Tacjana , Deja Mariusz
Published: March 2024

This article describes the application of the A-priori algorithm for defining the rule-based relationships between individual defects caused during the lamination process, affecting the deformation defect of the yacht shell. The data from 542 yachts were collected and evaluated. For the proper development of the algorithm, a technological process of the yacht lamination supported by expert decisions was described. The laminating technology is a complex process of a sequential application of individual laminates according to a special strategy. The A-priori algorithm allowed for obtaining the set of association rules defining the relationships between the defects resulting from the lamination process and influencing the deformation defect of the yacht shell, which is one of the most common errors in yacht production. The obtained aggregated rules were compared with the expert knowledge of the employees of the production, quality control, mould regeneration, and technology departments of the yacht yard. The use of the proposed A-priori algorithm allowed for the generation of relationship rules consistent with the general opinion of experts. Associative rules additionally took into account detailed causes of a specific error, which were not always noticed by employees of specific departments. The assessment of the lamination process using an artificial intelligence algorithm turned out to be more objective, which made it possible to gradually reduce the total number of errors occurring in the yacht shell lamination process, and thus shorten the time needed to repair errors and the total time of producing the yacht.
Exploring trajectories of functional decline and recovery among older adults: a data-driven approach
Authors: Khalili Ghazal , Zargoush Manaf , Huang Kai , Ghazalbash Somayeh
Published: March 2024

Independently performing activities of daily living (ADLs) is vital for maintaining one’s quality of life. Losing this ability can significantly impact an individual’s overall health status, including their mental health and social well-being. Aging is an important factor contributing to the loss of ADL abilities, and our study focuses on investigating the trajectories of functional decline and recovery in older adults. Employing trajectory analytics methodologies, this research delves into the intricate dynamics of ADL pathways, unveiling their complexity, diversity, and inherent characteristics. The study leverages a substantial dataset encompassing ADL assessments of nursing home residents with diverse disability profiles in the United States. The investigation begins by transforming these assessments into sequences of disability combinations, followed by applying various statistical measures, indicators, and visual analytics. Valuable insights are gained into the typical disability states, transitions, and patterns over time. The results also indicate that while predicting the progression of ADL disabilities presents manageable challenges, the duration of these states proves more complicated. Our findings hold significant potential for improving healthcare decision-making by enabling clinicians to anticipate possible patterns, develop targeted and effective interventions that support older patients in preserving their independence, and enhance overall care quality.
An efficient breast cancer classification model using bilateral filtering and fuzzy convolutional neural network
Authors: Hayum A. Abdul , Jaya J. , Sivakumar R. , Paulchamy B.
Published: March 2024

BC (Breast cancer) is the second most common reason for women to die from cancer. Recent workintroduced a model for BC classifications where input breast images were pre-processed using median filters for reducing noises. Weighed KMC (K-Means clustering) is used to segment the ROI (Region of Interest) after the input image has been cleaned of noise. Block-based CDF (Centre Distance Function) and CDTM (Diagonal Texture Matrix)-based texture and shape descriptors are utilized for feature extraction. The collected features are reduced in counts using KPCA (Kernel Principal Component Analysis). The appropriate feature selection is computed using ICSO (Improved Cuckoo Search Optimization). The MRNN ((Modified Recurrent Neural Network)) values are then improved through optimization before being utilized to divide British Columbia into benign and malignant types. However, ICSO has many disadvantages, such as slow search speed and low convergence accuracy and training an MRNN is a completely tough task. To avoid those problems in this work preprocessing is done by bilateral filtering to remove the noise from the input image. Bilateral filter using linear Gaussian for smoothing. Contrast stretching is applied to improve the image quality. ROI segmentation is calculated based on MFCM (modified fuzzy C means) clustering. CDTM-based, CDF-based color histogram and shape description methods are applied for feature extraction. It summarizes two important pieces of information about an object such as the colors present in the image, and the relative proportion of each color in the given image. After the features are extracted, KPCA is used to reduce the size. Feature selection was performed using MCSO (Mutational Chicken Flock Optimization). Finally, BC detection and classification were performed using FCNN (Fuzzy Convolutional Neural Network) and its parameters were optimized using MCSO. The proposed model is evaluated for accuracy, recall, f-measure and accuracy. This work’s experimental results achieve high values of accuracy when compared to other existing models.
A study on the influencing factors of corporate digital transformation: empirical evidence from Chinese listed companies
Authors: Zhao Xu , Chen Qi-an , Zhang Haitao , Chen Pengyu , Chen Shen
Published: March 2024

In an era where digital technology is reshaping business landscapes, understanding the factors that drive corporate digital transformation is essential. In this paper we explore these influencing factors, focusing on Chinese A-share listed companies from 2007 to 2021. Our approach involved a comprehensive analysis of multiple variables through regression techniques to determine their impact on digital transformation. The findings reveal the drive for reform in the digital transformation endeavours of enterprises. Notably, companies with higher gearing, overhead, and accounts receivable ratios exhibit a stronger inclination towards digital transformation. Conversely, enterprises in monopolistic industries and those at the inception stage of their life cycle show less propensity for such transformation. The findings of this research not only shed light on the strategic decisions behind digital transformation in response to financial and competitive challenges but also provide actionable insights for policymakers and business strategists. This study underscores the importance of contextualizing digital transformation efforts within the unique framework of industry characteristics and company development phases.
CD4+CD25+ regulatory T cells ex vivo generated from autologous naïve CD4+ T cells suppress EAE progression
Authors: Yang Ting-Ting , Liu Pen-Ju , Sun Qing-Yu , Wang Ze-Yi , Yuan Guo-Bin , Fan Ze-Xin , Ma Lin , Lu Jian-Feng , Yuan Bo-Yi , Zou Wen-Long , Zhao Li-Min , Li Qian , Liu Guang-Zhi
Published: March 2024

CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4+CD25highCD127low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 104 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS.
Effect of radiotherapy on head and neck cancer tissues in patients receiving radiotherapy: a bioinformatics analysis-based study
Authors: Guan Zhenjie , Liu Jie , Zheng Lian
Published: March 2024

Radiotherapy is pivotal in treating head and neck cancers including nasopharyngeal, tongue, hypopharyngeal, larynx, maxillary sinus, parotid gland, and oral cancers. It holds the potential for curative effects and finds application in conjunction with chemotherapy, either as a radical method to preserve organ function or as an adjuvant postoperative treatment. We used bioinformatics analysis to investigate the effects of radiotherapy on head and neck cancer tissues in patients who had received radiotherapy. In this study, the expression and mutation profiles of The Cancer Genome Atlas–Head-Neck Squamous Cell Carcinoma were downloaded from the UCSC-Xena database, categorizing patients into two groups—those receiving radiotherapy and those not receiving radiotherapy. Subsequently, differential expression analysis and gene set enrichment analysis (GSEA) were performed. Following this, single-sample GSEA (ssGSEA) scores related to glucose and lipid metabolism were compared between the two groups. Additionally, immune cell infiltration analysis and single-cell verification were performed. Finally, the mutation profiles of the two groups were compared. The analyses revealed that patients receiving radiotherapy exhibited prolonged survival, enhanced apoptosis in head and neck cancer tissue, and diminished keratinocyte proliferation and migration. A comparison of ssGSEA scores related to glucose and lipid metabolism between the two groups indicated a reduction in glycolysis, tricarboxylic acid cycle activity, and fat synthesis in tissues treated with radiotherapy, suggesting that radiotherapy can effectively inhibit tumour cell energy metabolism. Analyses of immune cell infiltration and single-cell verification suggested decreased infiltration of immune cells post-radiotherapy in head and neck cancer tissues. A comparison of mutation profiles revealed a higher frequency of TP53, TTN, and CDKN2A mutations in patients receiving radiotherapy for head and neck cancer. In conclusion, the bioinformatics analyses delved into the effect of radiotherapy on patients with head and neck carcinoma. This study provides a theoretical framework elucidating the molecular mechanisms underlying radiotherapy's efficacy in treating head and neck cancer and presents scientific recommendations for drug therapy following radiotherapy.
Prognostic factors of renal cell cancer in elderly patients: a population-based cohort study
Authors: Pajunen Heini , Veitonmäki Thea , Huhtala Heini , Nikkola Jussi , Pöyhönen Antti , Murtola Teemu
Published: March 2024

Mortality in renal cell cancer (RCC) is high in the elderly population. Comorbidities have a greater impact on overall prognosis of RCC among elderly patients than in younger patients. All new RCC cases were collected in people over 74 years of age between 1995 and 2018 from the Finnish cancer registry. The comorbidities were identified from the Care Registry for Healthcare. Charlson Comorbidity Index (CCI) was used to evaluate the risk of death based on comorbidities. The overall risk of death was analyzed using the Cox regression model. The risk for RCC death was analyzed using Fine and Gray regression analysis. Individual prognostic role of CCI components was evaluated by adding each component separately into the multivariable Fine and Gray regression model. Using the most prognostic comorbidities we constructed a nomogram to predict RCC mortality. Statistically significant prognostic factors of RCC death were tumor morphology (clear cell, papillary and chromophobe), sex, operative treatment, age, primary tumor extent and CCI. The strongest prognostic factors for overall mortality were tumor extent, tumor morphology and operative treatment. Among the components of CCI, the most important comorbidities predicting mortality were dementia, heart failure and kidney disease. The limitation of this study is that the comorbidities have only been recorded at inpatient and outpatient hospital contacts, which is why the prevalence of comorbidities is probably underestimated. In addition, physical performance status was not available from registry data, but it significantly affects the treatment decisions. RCC mortality is high in the elderly population. Among comorbidities, dementia and heart failure have the greatest impact on the prognosis. Curative treatment in selected elderly patients is efficient and should be considered in patients who can tolerate it and have only limited comorbidities.