bluuebunny/crossref_metadata_2025 huggingface dataset:
Study demands and resources affect academic well‐being and life satisfaction of undergraduate medical students in the Netherlands
Authors: Scheepers Renée A. , Hilverda Femke , Vollmann Manja
Published: June 2024

Introduction

Medical students report poor academic well‐being in a context of high study demands. Study Demands–Resources theories have outlined mediating processes involving high study demands and low resources to mitigate academic well‐being, which is subsequently associated with diminished overall well‐being (i.e. life satisfaction). Furthermore, academic well‐being and life satisfaction are also affected by interactions between study demands and resources (referred to as moderating processes). However, these mediating and moderating processes clarifying medical students' well‐being still need to be investigated. Therefore, this study investigated the mediating role of academic well‐being in the associations of study demands and resources with life satisfaction and the moderating role of study demands and resources in relation to academic well‐being and life satisfaction among undergraduate medical students.

Methods

In this cross‐sectional survey study, 372 undergraduates from Dutch medical schools participated. The survey included the Study Demands–Resources Scale (workload, growth opportunities and peer support) as well as questionnaires on academic well‐being (Utrecht Burnout Scale for students and Utrecht Work Engagement Scale‐Student Form) and overall well‐being (single item on life satisfaction). Based on Study Demands–Resources theories, (moderated) mediation analyses were performed.

Results

Mediating processes were found as growth opportunities were indirectly associated with higher life satisfaction through lower academic burnout and higher academic engagement. Furthermore, workload was indirectly associated with lower life satisfaction through higher academic burnout. This association was moderated as it became weaker with more perceived peer support.

Discussion

A high workload and limited growth opportunities are associated with suboptimal academic well‐being and life satisfaction. Perceiving support from peer students slightly buffers the unfavourable effect of workload on academic burnout and subsequently life satisfaction. To promote academic well‐being and life satisfaction in medical students, universities can consider to reduce the workload, to create a supportive learning environment and to offer development opportunities.
Identification and distribution of some medico‐veterinary important pathogens in muscid flies in two geographical regions of Türkiye
Authors: Ercan Nuri , Yildirim Alparslan , Duzlu Onder , Ercan Fahriye , Yetismis Gamze , Pekmezci Gokmen Zafer , Inci Abdullah
Published: June 2024

Some dipteran flies play an important role in the transmission of pathogens such as viruses, bacteria, fungi, protozoan and metazoan parasites in humans and other animals. Despite this importance, knowledge of the prevalence and molecular characteristics of some pathogens in flies is limited, and no data are available for Türkiye. In this study, we investigated the possible vector role of muscid fly species for the transmission of Enterocytozoon bieneusi Desportes (Chytridiopsida: Enterocytozoonidae), Encephalitozoon spp., Coxiella burnetii Derrick (Legionellales: Coxiellaceae) and Thelazia spp. using polymerase chain reaction (PCR) and sequence analysis. The flies were trapped in different animal‐related places and surroundings from two different geographical regions of Türkiye including Central Anatolia and Middle Black Sea. According to the morphological keys, 850 (85%), 141 (14.1%) and 6 (0.6%) of the total of 1000 fly specimens identified as Musca domestica Linnaeus (Diptera: Muscidae), Stomoxys calcitrans Linnaeus (Diptera: Muscidae) and Musca autumnalis De Geer (Diptera: Muscidae), respectively. The other species including Haematobia irritans Linnaeus (Diptera: Muscidae), Muscina stabulans Fallén (Diptera: Muscidae) and Hydrotaea ignava Harris (Diptera: Muscidae) were each represented by a single specimen. Screening of the pathogens identified E. bieneusi only in M. domestica with a prevalence of 2.4%. Sequence analyses identified three known genotypes, Type IV, BEB6 and BEB8, and one novel genotype named AEUEb of E. bieneusi in M. domestica. Coxiella burnetii was detected in M. domestica and S. calcitrans with prevalences of 2.9% and 2.8%, respectively. The one specimen of H. ignava was also positive for C. burnetii. Encephalitozoon spp. and Thelazia spp. were not found in the examined specimens. Our results contribute to the current knowledge on the vector potential of muscid flies and their possible role in the transmission dynamics of certain pathogens, especially in regions where diseases are prevalent and affect public and animal health.
Genome‐wide analysis of salicylic acid and jasmonic acid signalling marker gene families in wheat
Authors: Heckmann A. , Perochon A. , Doohan F. M.
Published: June 2024

Jasmonic acid (JA) and salicylic acid (SA) phytohormone pathways are important regulators of stress tolerance. Knowledge regarding the diversity, phylogeny and functionality of wheat genes involved in JA and SA response is limited.

Using Arabidopsis, rice and wheat genomic and wheat disease transcriptomic data, we deduced the size, phylogenetic diversity and pathogen‐responsiveness of seven hormone‐responsive gene families, and thus selected 14 candidates as potential hormone responsive gene markers. Gene‐specific expression studies assessed the impact of exogenous JA and SA on their transcriptional activation in leaves of two distinct wheat cultivars. RNAseq data were interrogated to assess their disease responsiveness and tissue‐specific expression.

This study elucidated the number, phylogeny and pathogen‐responsiveness of wheat genes from seven families, including 12 TaAOS, 6 TaJAMyb, 256 TaWRKY group III, 85 TaPR1, 205 TaPR2, 76 TaPR3 and 124 TaPR5. This included the first description of the wheat AOS, JAMyb, PR2, PR3 and PR5 gene families. Gene expression studies delineated TaAOS1‐5B and TaJAMyb‐4A as JA‐responsive in leaves, but not significantly responsive to SA treatment, while TaWRKY45‐B was a SA‐ but not a JA‐responsive marker. Other candidate genes were either unresponsive or non‐specific to SA or JA.

Our findings highlight that all seven gene families are greatly expanded in wheat as compared to other plants (up to 7.6‐fold expansion), and demonstrate disparity in the response to biotic stress between some homoeologous and paralogous sequences within these families. The SA‐ and JA‐responsive marker genes identified herein will prove useful tools to monitor these signalling pathways in wheat.
Examining social vulnerability to multi‐hazards in North‐Western Himalayas, India
Authors: Sharma Lucky , Rana Narendra Kumar , Dube Shiva Kant
Published: June 2024

The enhancing risk from human action and multi‐hazard interaction has substantially complicated the hazard–society relationship. The underlying vulnerabilities are crucial in predicting the probable impact to be caused by multi‐hazards. Thus, the evaluation of social vulnerability is decisive in inferring the driving factor and preparing for mitigation strategies. The Himalayan landscape is prone to multiple hazards as well as possesses a multitude of vulnerabilities owing to changing human landscape. Thus, an attempt has been made to inquire into the underlying socioeconomic factors enhancing the susceptibility of the region to multi‐hazards. The social vulnerability index (SVIent) has been introduced, consisting of 13 indicators and 33 variables. The variables have been standardized using the maximum and minimum normalization method and the relative importance for each indicator has been determined using Shannon entropy methods to compute SVIent. The findings revealed that female population, population above 60 years old, net irrigated area, migrant population, dilapidated house, nonworkers, bank, and nonworkers seeking jobs were found to be relatively significant contributors to the vulnerability. The western part of the study area was classified as the highly vulnerable category (SVI > 0.40628), attributed to high dependence, and higher share of unemployed workers and high poverty. The SVIent was shown to have positive correlation between unemployment, socioeconomic status, migration, dependency, and household structure significant at two‐tailed test. The study's impact can be found in influencing the decision of policymakers and stakeholders in framing the mitigation strategies and policy documents.
Investigating the effects of spatial scales on social vulnerability index: A hybrid uncertainty and sensitivity analysis approach combined with remote sensing land cover data
Authors: He Bowen , Guan Qun
Published: June 2024

Investigating the effects of spatial scales on the uncertainty and sensitivity analysis of the social vulnerability index (SoVI) model output is critical, especially for spatial scales finer than the census block group or census block. This study applied the intelligent dasymetric mapping approach to spatially disaggregate the census tract scale SoVI model into a 300‐m grids resolution SoVI map in Davidson County, Nashville. Then, uncertainty analysis and variance‐based global sensitivity analysis were conducted on two scales of SoVI models: (a) census tract scale; (b) 300‐m grids scale. Uncertainty analysis results indicate that the SoVI model has better confidence in identifying places with a higher socially vulnerable status, no matter the spatial scales in which the SoVI is constructed. However, the spatial scale of SoVI does affect the sensitivity analysis results. The sensitivity analysis suggests that for census tract scale SoVI, the indicator transformation and weighting scheme are the two major uncertainty contributors in the SoVI index modeling stages. While for finer spatial scales like the 300‐m grid's resolution, the weighting scheme becomes the uttermost dominant uncertainty contributor, absorbing uncertainty contributions from indicator transformation.
For a United Russia? The White Movement’s Rejection of National Self‐Determination, 1918–20
Authors: Rowe Oliver
Published: June 2024

For obvious reasons, the White Movement rarely features in works concerning national self‐determination in the aftermath of the First World War. Beyond the looming shadows of Woodrow Wilson and V. I. Lenin, the “governments” of White generals that swore allegiance to A. V. Kolchak made no secret of their desire for a Russia “one and indivisible.” Those responsible for drafting Omsk’s edicts were suspicious of self‐determination’s apparent Germano‐Bolshevik origins. Analyzing the so‐called Russian state’s resistance to both the term and concept of national self‐determination—and its relatively novel association with secession—highlights the self‐defeating nature of Kolchak’s policies on the matter. Moreover, and most significantly for wider discussions on national self‐determination during the period, the White Movement’s rejection of federalism in any form, coupled with the stalling progress of White armies, the conclusion of the Paris Peace Conference, and the consolidation of Soviet Russia made statehood for Russia’s neighbor nations more realistic, logical, and justifiable. The political failures of the White Movement contributed to the feasibility of small states in the eyes of both the Allies and the national peoples themselves, and this warrants attention.
Integration of C3H15‐mediated transcriptional and post‐transcriptional regulation confers plant thermotolerance in Arabidopsis
Authors: Chai Guohua , Liu Huanhuan , Zhang Yang , Wang Congpeng , Xu Hua , He Guo , Meng Jie , Tang Xianfeng , Wang Dian , Zhou Gongke
Published: June 2024

Heat stress is an environmental factor that significantly threatens crop production worldwide. Nevertheless, the molecular mechanisms governing plant responses to heat stress are not fully understood. Plant zinc finger CCCH proteins have roles in stress responses as well as growth and development through protein–RNA, protein–DNA, and protein–protein interactions. Here, we reveal an integrated multi‐level regulation of plant thermotolerance that is mediated by the CCCH protein C3H15 in Arabidopsis. Heat stress rapidly suppressed C3H15 transcription, which attenuated C3H15‐inhibited expression of its target gene HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2), a central regulator of heat stress response (HSR), thereby activating HEAT SHOCK COGNATE 70 (HSC70.3) expression. The RING‐type E3 ligase MED25‐BINDING RING‐H2 PROTEIN 2 (MBR2) was identified as an interacting partner of C3H15. The mbr2 mutant was susceptible to heat stress compared to wild‐type plants, whereas plants overexpressing MBR2 showed increased heat tolerance. MBR2‐dependent ubiquitination mediated the degradation of phosphorylated C3H15 protein in the cytoplasm, which was enhanced by heat stress. Consistently, heat sensitivities of C3H15 overexpression lines increased in MBR2 loss‐of‐function and decreased in MBR2 overexpression backgrounds. Heat stress‐induced accumulation of HSC70.3 promoted MBR2‐mediated degradation of C3H15 protein, implying that an auto‐regulatory loop involving C3H15, HSFA2, and HSC70.3 regulates HSR. Heat stress also led to the accumulation of C3H15 in stress granules (SGs), a kind of cytoplasmic RNA granule. This study advances our understanding of the mechanisms plants use to respond to heat stress, which will facilitate technologies to improve thermotolerance in crops.
A novel three‐layer module BoMYB1R1‐BoMYB4b/BoMIEL1‐BoDFR1 regulates anthocyanin accumulation in kale
Authors: Liu Yang , Jin Hangbiao , Zhang Yuting , Feng Xin , Dai Yujia , Zhu Pengfang
Published: June 2024

Anthocyanin is an important pigment responsible for plant coloration and beneficial to human health. Kale (Brassica oleracea var. acephala), a primary cool‐season flowers and vegetables, is an ideal material to study anthocyanin biosynthesis and regulation mechanisms due to its anthocyanin‐rich leaves. However, the underlying molecular mechanism of anthocyanin accumulation in kale remains poorly understood. Previously, we demonstrated that BoDFR1 is a key gene controlling anthocyanin biosynthesis in kale. Here, we discovered a 369‐bp InDel variation in the BoDFR1 promoter between the two kale inbred lines with different pink coloration, which resulted in reduced transcriptional activity of the BoDFR1 gene in the light‐pink line. With the 369‐bp insertion as a bait, an R2R3‐MYB repressor BoMYB4b was identified using the yeast one‐hybrid screening. Knockdown of the BoMYB4b gene led to increased BoDFR1 expression and anthocyanin accumulation. An E3 ubiquitin ligase, BoMIEL1, was found to mediate the degradation of BoMYB4b, thereby promoting anthocyanin biosynthesis. Furthermore, the expression level of BoMYB4b was significantly reduced by light signals, which was attributed to the direct repression of the light‐signaling factor BoMYB1R1 on the BoMYB4b promoter. Our study revealed that a novel regulatory module comprising BoMYB1R1, BoMIEL1, BoMYB4b, and BoDFR1 finely regulates anthocyanin accumulation in kale. The findings aim to establish a scientific foundation for genetic improvement of leaf color traits in kale, meanwhile, providing a reference for plant coloration studies.
Presentation, diagnosis, and outcomes of cats undergoing surgical treatment of ectopic ureters
Authors: Cortez Gabriela L. , Thomson Christopher B. , Scharf Valery F. , Berent Allyson , Buote Nicole J. , Carson Brittney A. , Cassandra Margaret , Mayhew Philipp D. , Singh Ameet
Published: June 2024

Objective

To describe the signalment, treatment, complications, and outcomes of cats treated surgically for ectopic ureters.

Study design

Retrospective, multi‐institutional study.

Animals

Twelve client‐owned cats.

Methods

Medical records of cats diagnosed with unilateral or bilateral ectopic ureters were reviewed and analyzed. Data reported included signalment, clinical signs, diagnostics, open celiotomy, or cystoscopic surgical interventions, and outcomes.

Results

Seven of the 12 cats in the study population were female or female spayed and the median age at time of presentation was 4 years, with an interquartile range (IQR) of 6 months–14 years. Presurgical diagnostic imaging diagnosed ectopic ureters by abdominal ultrasound (8/10), contrast enhanced computed tomography (3/3), fluoroscopic urography (3/4), or cystoscopy (6/7). Eight of 12 cats had extramural ectopic ureters and six cats were affected bilaterally. Eight affected cats underwent ureteroneocystostomy, one cat underwent neoureterostomy, two cats underwent cystoscopic laser ablation, and one cat underwent nephroureterostomy. Immediate postoperative complications occurred in three cats; one cat required additional surgical intervention. Short‐term complications occurred in three cats, and long‐term complications in two cats. All cats that underwent surgical or cystoscopic intervention had improvement of their urinary incontinence scores, with complete resolution in 11 cats.

Conclusion

Surgical correction of ectopic ureters in cats is associated with good long‐term outcomes. Ectopic ureters in cats are commonly extramural and bilateral. Postoperative outcomes were acceptable and there were few postoperative complications, with varying forms of surgical correction.

Clinical significance

Ectopic ureters in cats are rare but urinary incontinence can be corrected or improved successfully with surgery.
Numerical Investigation of Flow Evolution in Centrifugal Compressors During Surge
Authors: Zhang Meijie , Wu Wangxia , Zhou Chao
Published: June 2024

Surge can lead to violent flow fluctuations in the compression system and damage to the blade structures. In this article, a fully three-dimensional numerical model of the centrifugal compressor surge is developed, and the accurate transient flow evolutions in different components during the surge are studied in detail. The results show that in the surge initiation, the pressure distortion caused by the asymmetric geometry of the volute at the diffuser outlet transfers along blade passages to the impeller inlet, which induces two types of stall cells with different rotating speeds and sizes developing independently in two isolated circumferential positions at the impeller inlet. With the surge development, the two types of stall cells come into contact and are mixed, which causes the asymmetric local reverse flow near the casing of the impeller leading edge. Subsequently, the reverse flow extends to the full annuls at the impeller inlet, and the compressor pressure ratio falls abruptly. At the same time, several expansion waves arise in the impeller and travel downstream along the volute and the outlet pipe. As reflected by the nozzle, these expansion waves travel back upstream into the impeller. The findings of this research have great implications for the asymmetric flow control methods, which develop novel asymmetric geometries to counteract the influence of the volute and extend the compressor stable operation range.
From Frozen Ponds to Organized Competitions: The Growth of Skating and Ice Hockey in Korea, 1886–1938
Authors: Park Kyoungho , Lee Karam
Published: June 2024

The encounter of American Protestant evangelicalism and Japanese imperialism formed in Korean society in the late 19th and early 20th centuries became a steppingstone for the acceptance of modern winter sports in Korea. In particular, skates introduced by American Protestant missionaries and the Young Men’s Christian Association formed an imaginary space to counter Japanese imperialism in Korea during Japanese colonial era. Ice hockey introduced along with skating is a representative product that evolved in this process. The history of the introduction of American ice hockey to Korea also had a dual imperial influence between the United States and Japan, and in another direction, there was a voluntary acceptance process by Koreans who recognized ice hockey as a modern product.
Lattice-guided assembly of optoelectronically active π-conjugated peptides on 1D van der Waals single crystals
Authors: Yao Ze-Fan , Cordova Dmitri Leo Mesoza , Milligan Griffin M. , Lopez Diana , Allison Steven Jay , Kuang Yuyao , Ardoña Herdeline Ann M. , Arguilla Maxx Q.
Published: June 2024

The deployment of organic molecules in high-performance devices strongly relies on the formation of well-ordered domains, which is often complicated by the dynamic and sensitive nature of supramolecular interactions. Here, we engineered the assembly of water-processable, optoelectronic π-conjugated peptides into well-defined organic-inorganic heterointerfaced assemblies by leveraging the long-range anisotropic ordering of 1D van der Waals (vdW) crystals composed of subnanometer-thick transition metal sulfide chains (MS
3
; M = Nb, Ta) as assembly templates. We found that the monomers can readily form 1D supramolecular assemblies onto the underlying crystal surface, owing to the structural correspondence between the π-π interactions of the quaterthiophene (4T)–based peptide units (DDD-4T) and sulfur atom ordering along the NbS
3
(100) surface. The heterointerfaced assemblies exhibited substantially red-shifted photoluminescence and enhanced visible-range photocurrent generation compared to solution-assembled films. Our results underscore the role of lattice matching in forming ordered supramolecular assemblies, offering an emergent approach to assembling organic building blocks endowed with improved physical properties.
Biohybrid microrobots locally and actively deliver drug-loaded nanoparticles to inhibit the progression of lung metastasis
Authors: Zhang Fangyu , Guo Zhongyuan , Li Zhengxing , Luan Hao , Yu Yiyan , Zhu Audrey T. , Ding Shichao , Gao Weiwei , Fang Ronnie H. , Zhang Liangfang , Wang Joseph
Published: June 2024

Lung metastasis poses a formidable challenge in the realm of cancer treatment, with conventional chemotherapy often falling short due to limited targeting and low accumulation in the lungs. Here, we show a microrobot approach using motile algae for localized delivery of drug-loaded nanoparticles to address lung metastasis challenges. The biohybrid microrobot [denoted “algae-NP(DOX)-robot”] combines green microalgae with red blood cell membrane–coated nanoparticles containing doxorubicin, a representative chemotherapeutic drug. Microalgae provide autonomous propulsion in the lungs, leveraging controlled drug release and enhanced drug dispersion to exert antimetastatic effects. Upon intratracheal administration, algae-NP(DOX)-robots efficiently transport their drug payload deep into the lungs while maintaining continuous motility. This strategy leads to rapid drug distribution, improved tissue accumulation, and prolonged retention compared to passive drug-loaded nanoparticles and free drug controls. In a melanoma lung metastasis model, algae-NP(DOX)-robots exhibit substantial improvement in therapeutic efficacy, reducing metastatic burden and extending survival compared to control groups.
A portable inflatable soft wearable robot to assist the shoulder during industrial work
Authors: Zhou Yu Meng , Hohimer Cameron J. , Young Harrison T. , McCann Connor M. , Pont-Esteban David , Civici Umut S. , Jin Yichu , Murphy Patrick , Wagner Diana , Cole Tazzy , Phipps Nathan , Cho Haedo , Bertacchi Franchesco , Pignataro Isabella , Proietti Tommaso , Walsh Conor J.
Published: June 2024

Repetitive overhead tasks during factory work can cause shoulder injuries resulting in impaired health and productivity loss. Soft wearable upper extremity robots have the potential to be effective injury prevention tools with minimal restrictions using soft materials and active controls. We present the design and evaluation of a portable inflatable shoulder wearable robot for assisting industrial workers during shoulder-elevated tasks. The robot is worn like a shirt with integrated textile pneumatic actuators, inertial measurement units, and a portable actuation unit. It can provide up to 6.6 newton-meters of torque to support the shoulder and cycle assistance on and off at six times per minute. From human participant evaluations during simulated industrial tasks, the robot reduced agonist muscle activities (anterior, middle, and posterior deltoids and biceps brachii) by up to 40% with slight changes in joint angles of less than 7% range of motion while not increasing antagonistic muscle activity (latissimus dorsi) in current sample size. Comparison of controller parameters further highlighted that higher assistance magnitude and earlier assistance timing resulted in statistically significant muscle activity reductions. During a task circuit with dynamic transitions among the tasks, the kinematics-based controller of the robot showed robustness to misinflations (96% true negative rate and 91% true positive rate), indicating minimal disturbances to the user when assistance was not required. A preliminary evaluation of a pressure modulation profile also highlighted a trade-off between user perception and hardware demands. Finally, five automotive factory workers used the robot in a pilot manufacturing area and provided feedback.
Anti–PD-1 cancer immunotherapy induces central nervous system immune-related adverse events by microglia activation
Authors: Vinnakota Janaki Manoja , Adams Rachael C. , Athanassopoulos Dimitrios , Schmidt Dominik , Biavasco Francesca , Zähringer Alexander , Erny Daniel , Schwabenland Marius , Langenbach Marlene , Wenger Valentin , Salié Henrike , Cook James , Mossad Omar , Andrieux Geoffroy , Dersch Rick , Rauer Sebastian , Duquesne Sandra , Monaco Gianni , Wolf Phillipp , Blank Thomas , Häne Philipp , Greter Melanie , Becher Burkhard , Henneke Philipp , Pfeifer Dietmar , Blazar Bruce R. , Duyster Justus , Boerries Melanie , Köhler Natalie , Chhatbar Chintan M. , Bengsch Bertram , Prinz Marco , Zeiser Robert
Published: June 2024

Cancer treatment with anti–PD-1 immunotherapy can cause central nervous system immune-related adverse events (CNS-irAEs). The role of microglia in anti–PD-1 immunotherapy–induced CNS-irAEs is unclear. We found that anti–PD-1 treatment of mice caused morphological signs of activation and major histocompatibility complex (MHC) class II up-regulation on microglia. Functionally, anti–PD-1 treatment induced neurocognitive deficits in mice, independent of T cells, B cells, and natural killer cells. Instead, we found that microglia mediated these CNS-irAEs. Single-cell RNA sequencing revealed major transcriptional changes in microglia upon anti–PD-1 treatment. The anti–PD-1 effects were mediated by anti–PD-1 antibodies interacting directly with microglia and were not secondary to peripheral T cell activation. Using a proteomics approach, we identified spleen tyrosine kinase (Syk) as a potential target in activated microglia upon anti–PD-1 treatment. Syk inhibition reduced microglia activation and improved neurocognitive function without impairing anti-melanoma effects. Moreover, we analyzed CNS tissue from a patient cohort that had received anti–PD-1 treatment. Imaging mass cytometry revealed that anti–PD-1 treatment of patients was associated with increased surface marker expression indicative of microglia activation. In summary, we identified a disease-promoting role for microglia in CNS-irAEs driven by Syk and provide an inhibitor-based approach to interfere with this complication after anti–PD-1 immunotherapy.
In vitro
activity of taurolidine against clinical
Candida auris
isolates: relevance to catheter-related bloodstream infections
Authors: Reidenberg Bruce E. , Jenkins Stephen G. , Crandon Jared L. , Hurlburt Elizabeth , Tan Xing , Rhomberg Paul R. , Arends S. J. Ryan , Pfaffle Antony
Published: June 2024

Candida auris
is an evolving and concerning global threat. Of particular concern are bloodstream infections related to central venous catheters. We evaluated the activity of taurolidine, a broad-spectrum antimicrobial in catheter lock solutions, against 106
C
.
auris
isolates. Taurolidine was highly active with a MIC
50
/MIC
90
of 512/512 mg/L, over 20-fold lower than lock solution concentrations of ≥13,500 mg/L. Our data demonstrate a theoretical basis for taurolidine-based lock solutions for prevention of
C. auris
catheter-associated infections.
PA-824 inhibits porcine epidemic diarrhea virus infection
in vivo
and
in vitro
by inhibiting p53 activation
Authors: Li Liang , Li Hongyue , Qiu Yanping , Li Jie , Zhou Yi , Lv Muze , Xiang Hongwei , Bo Zongyi , Shen Haixiao , Sun Pei
Published: June 2024

Porcine epidemic diarrhea virus (PEDV) is a type A coronavirus that causes severe watery diarrhea in piglets, resulting in severe economic losses worldwide. Therefore, new approaches to control PEDV infection are essential for a robust and sustainable pig industry. We screened 314 small-molecule drug libraries provided by Selleck and found that four drugs had obviously inhibitory effects on PEDV in Vero cells. PA-824, which had the highest SI index and the most reliable clinical safety, was selected for
in vivo
experiments. Animal attack tests showed that PA-824 effectively alleviated the clinical signs, intestinal pathological changes, and inflammatory responses in lactating piglets after PEDV infection. To further investigate the antiviral mechanism of PA-824, we measured the inhibitory effect of PA-824 on PEDV proliferation in a dose-dependent manner. By exploring the effect of PA-824 on the PEDV life cycle, we found that PA-824 acted directly on viral particles and hindered the adsorption, internalization, and replication phases of the virus, followed by molecular docking analysis to predict the interaction between PA-824 and PEDV non-structural proteins. Finally, we found that PA-824 could inhibit the apoptotic signaling pathway by suppressing PEDV-induced p53 activation. These results suggest that PA-824 could be protective against PEDV infection in piglets and could be developed as a drug or a feed additive to prevent and control PEDV diseases.

IMPORTANCE

PEDV is a highly contagious enteric coronavirus that widely spread worldwide, causing serious economic losses. There is no drug or vaccine to effectively control PEDV. In this study, we found that PA-824, a compound of mycobacteria causing pulmonary diseases, inhibited PEDV proliferation in both
in vitro
and
in vivo
. We also found that PA-824 directly acted on viral particles and hindered the adsorption, internalization, and replication stages of the virus. In addition, we found that PA-824 could inhibit the apoptotic signaling pathway by inhibiting PEDV-induced p53 activation. In conclusion, it is expected to be developed as a drug or a feed additive to prevent and control PEDV diseases.
Assessing the risks for stillbirth in São Paulo, Brazil: protocol for a multidisciplinary case–control study – FetRisks
Authors: Buralli Rafael Junqueira , da Silva Zilda Pereira , Alencar Gizelton Pereira , Figueiredo Gerusa Maria , Hoshida Mara Sandra , Luna Expedito J. A. , Pastro Luciana Duzolina Manfré , Santos Osmara Alves dos , Marques Lays Janaina Prazeres , Zerbinati Rodrigo Melim , Galisteo Junior Andrés Jimenez , Andrade Junior Heitor de , Machado Clarisse M , Meireles Luciana Regina , Schultz Regina , Rodrigues Laura Cunha , Francisco Rossana Pulcineli Vieira , Novaes Hillegonda Maria Dutilh , Almeida Marcia Furquim de , Gouveia Nelson
Published: June 2024

Stillbirth is a fundamental component of childhood mortality, but its causes are still insufficiently understood. This study aims to explore stillbirth risk factors by using a multidisciplinary approach to stimulate public policies and protocols to prevent stillbirth, improve maternal care and support bereaved families.

Methods and analysis

In this case–control study with stillbirths and live births in 14 public hospitals in São Paulo, mothers are interviewed at hospitals after delivery, and hospital records and prenatal care registries are reviewed. Maternal and umbilical cord blood samples and placentas are collected to analyse angiogenesis and infection biomarkers, and the placenta’s anatomopathological exam. Air pollutant exposure is estimated through the participant’s residence and work addresses. Traditional and non-invasive autopsies by image-guided histopathology are conducted in a subset of stillbirths. Subsample mothers of cases are interviewed at home 2 months after delivery on how they were dealing with grief. Information contained in the official prenatal care registries of cases and controls is being compiled. Hospital managers are interviewed about the care offered to stillbirth mothers. Data analysis will identify the main risk factors for stillbirth, investigate their interrelations, and evaluate health services care and support for bereaved families. We hope this project will contribute to the understanding of stillbirth’s risk factors and related health services in Brazil, providing new knowledge about this central public health problem, contributing to the improvement of public policies and prenatal and puerperal care, helping to prevent stillbirths and improve the healthcare and support for bereaved families.

Ethics and dissemination

This study protocol was approved by the Ethics Committee of the Municipal Health Secretary (process no 16509319.0.3012.5551) and of the Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (process no 16509319.0.0000.0068). Results will be communicated to the study participants, policy-makers and the scientific community.
TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer’s disease
Authors: Vuoksimaa Eero , Saari Toni T , Aaltonen Aino , Aaltonen Sari , Herukka Sanna-Kaisa , Iso-Markku Paula , Kokkola Tarja , Kyttälä Aija , Kärkkäinen Sari , Liedes Hilkka , Ollikainen Miina , Palviainen Teemu , Ruotsalainen Ilona , Toivola Auli , Urjansson Mia , Vasankari Tommi , Vähä-Ypyä Henri , Forsberg Markus M , Hiltunen Mikko , Jalanko Anu , Kälviäinen Reetta , Kuopio Teijo , Lähteenmäki Jaakko , Nyberg Pia , Männikkö Minna , Serpi Raisa , Siltanen Sanna , Palotie Aarno , Kaprio Jaakko , Runz Heiko , Julkunen Valtteri
Published: June 2024

Introduction

A better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria.

Methods and analysis

A multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN.

Ethics and dissemination

This recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.
Is home-based, virtually delivered, group exercise feasible and acceptable for older patients with hepatocellular carcinoma? A non-randomised feasibility study (TELEX-Liver Cancer)
Authors: Hallsworth Kate , McCain Misti V , Fallen-Bailey Roisin , Brown Morven C , Orange Samuel T , Reeves Helen L
Published: June 2024

Objectives

The study aimed to assess the feasibility, acceptability and safety of delivering a home-based telehealth exercise intervention to older patients with hepatocellular carcinoma (HCC).

Design

Non-randomised feasibility study.

Setting

Patients were recruited from UK outpatient liver cancer clinics.

Participants

Patients were aged ≥60 years with HCC, with post-treatment imaging reporting a complete response, partial response or stable disease.

Intervention and data collection

Patients were invited to attend synchronous online exercise sessions, twice weekly for 10 weeks. Physical function and patient-reported outcomes were assessed pre-intervention and post-intervention. Qualitative data were collected via semistructured interviews after intervention completion.

Primary outcome measures

Recruitment, retention, exercise adherence and safety.

Results

40 patients were invited to participate and 19 (mean age 74 years) provided consent (recruitment rate 48%). Patients completed 76% of planned exercise sessions and 79% returned to the clinic for follow-up. Hand grip strength (95% CI 1.0 to 5.6), Liver Frailty Index (95% CI −0.46 to –0.23) and time taken to perform five sit-to-stands (95% CI −3.2 to –1.2) improved from pre-intervention to post-intervention. Patients reported that concerns they had relating to their cancer had improved following the intervention (95% CI 0.30 to 5.85). No adverse events occurred during exercise sessions.

Qualitative data highlighted the importance of an instructor in real time to ensure that the sessions were achievable, tailored and well balanced, which helped to foster motivation and commitment within the group. Patients reported enjoying the exercise intervention, including the benefits of peer support and highlighted perceived benefits to both their physical and mental health. Patients felt that the online sessions overcame some of the barriers to exercise participation and preferred attending virtual sessions over face-to-face classes.

Conclusions

It is feasible, acceptable and safe to deliver supervised group exercise via videoconferencing to patients with HCC in their own homes. These findings will inform the design of a future, adequately powered randomised controlled trial to evaluate the efficacy of the intervention.

Trial registration number

ISRCTN14411809.
Rheological bridge zones: the initiation of strain localization
Authors: Feng He , Gerbi Christopher C. , Johnson Scott E. , Cruz-Uribe Alicia M. , Yates Martin G.
Published: June 2024

Strain localization occurs across the crust in both brittle and viscous regimes, but the exact causes remain debated. Natural rock observations suggest that changes in phase properties (such as physical properties, phase distribution, and grain geometry) are more influential in weakening than variations in stress and temperature. Investigating the early stages of strain accumulation in various pressure–temperature conditions leads to a better understanding of these causes. Our study focuses on three weakly deformed rocks showing zones of localization on a millimeter or smaller scale, which we term “bridge zones”. These localized zones appear to mechanically connect weak domains and typically exhibit finer grain sizes within a narrow band. Importantly, these zones occur in less deformed rocks from the margins of shear zones. They result from both in situ grain size reduction and chemical processes leading to phase mixing or element mobility on a limited spatial scale. Numerical modeling aligns high-stress areas with these zones, supporting their impact on reducing rock strength. We propose a conceptual model linking far-field loading to microscale changes in developing these zones. Characterization of bridge zones aids in elucidating the microstructural processes driving deformation localization, which is fundamental for plate tectonics, metamorphism, seismicity, and other lithospheric processes. This research reveals microscale mechanisms driving weak domain development, improving our knowledge of rheological changes and laying the groundwork for predictive models regarding strength evolution in the lithosphere.
Spectral properties and photophysical processes of triphenylamine-porphyrin-pyrimidine triads
Authors: Liu Xinrui , Gong Kun , Liu Shiling , Liu Dongzhi , Li Wei , Zhou Xueqin
Published: June 2024

Porphyrins have attracted considerable attention as an important family of photosensitizers used for dye-sensitized solar cells (DSSCs). In this work, a novel triphenylamine-porphyrin-pyrimidine triad with a triple bond linkage was synthesized and characterized. The sensitizer presents broad absorption in solution and on TiO2 films across the UV-Vis region benefiting from the extended conjugation. The acetenyl [Formula: see text]-conjugated bridge stimulates the photoinduced electron transfer (PET) process and brings a charge-separated state lifetime of around 4 μs. DSSC devices based on the sensitizer achieve a power conversion efficiency (PCE) of 3.77% thanks to the prolonged charge-separated state lifetime and suppressed charge recombination. The understanding of the structural, optical, and electrochemical properties of triphenylamine-porphyrin-pyrimidine triads provides new insights into the rational design of porphyrin sensitizers for various applications.
MET-MAPF: A Metamorphic Testing Approach for Multi-Agent Path Finding Algorithms
Authors: Zhang Xiao-Yi , Liu Yang , Arcaini Paolo , Jiang Mingyue , Zheng Zheng
Published: June 2024

The Multi-Agent Path Finding (MAPF) problem, i.e., the scheduling of multiple agents to reach their destinations, has been widely investigated. Testing MAPF systems is challenging, due to the complexity and variety of scenarios and the agents’ distribution and interaction. Moreover, MAPF testing suffers from the oracle problem, i.e., it is not always clear whether a test shows a failure or not. Indeed, only considering whether the agents reach their destinations without collision is not sufficient. Other properties related to the ‘quality’ of the generated paths should be assessed, e.g., an agent should not follow an unnecessarily long path. To tackle this issue, this article proposes MET-MAPF, a Metamorphic Testing approach for MAPF systems. We identified 10 Metamorphic Relations (MRs) that a MAPF system should guarantee, designed over the environment in which agents operate, the behaviour of the single agents and the interactions among agents. Starting from the different MRs, MET-MAPF automatically generates test cases addressing them, so possibly exposing different types of failures. Experimental results show that MET-MAPF can indeed find MR violations not exposed by approaches that only consider the completion of the mission as test oracle. Moreover, experiments show that different MRs expose different types of violations.
Energy and QoE Optimization for Mobile Video Streaming with Adaptive Brightness Scaling
Authors: Liu Daibo , Qian Chao , Rong Huigui , Zhou Siwang , Xiang Chaocan , Jiang Hongbo
Published: June 2024

Brightness scaling (BS) is an emerging and promising technique with outstanding energy efficiency on mobile video streaming. However, existing BS-based approaches totally neglect the inherent interaction effect between BS factor, video bitrate and environment context. Their combined impact on user’s visual perception in mobile scenario, leading to inharmonious between energy consumption and user’s quality of experience (QoE). In this paper, we propose
PEO
, a novel user-
P
erception-based video
E
xperience
O
ptimization for energy-constrained mobile video streaming, by jointly considering the inherent connection between a device’s state of motion, video quality and the resulting user-perceived quality. Specifically, by capturing the motion of the on-the-run device, PEO first infers the optimal bitrate and BS factor, therefore avoiding bitrate-inefficiency for energy saving while guaranteeing the user-perceived QoE. On that basis, we formulate the device motion-aware and user perception-aware video streaming as an optimization problem where we present an optimal algorithm to maximize the object function and adapt to user preference, and thus propose an online bitrate selection algorithm. Our evaluation (based on trace analysis and user study) shows that, compared with state-of-the-art techniques, PEO can raise the perceived quality by 23.8%-41.3% and save up to 25.2% energy consumption.
Multi-Grained Point Cloud Geometry Compression via Dual-Model Prediction with Extended Octree
Authors: Qin Tai , Li Ge , Gao Wei , Liu Shan
Published: June 2024

The state-of-the-art geometry-based point cloud compression (G-PCC) (Octree) is the fine-grained approach, which uses the octree to partition point clouds into voxels and predicts them based on neighbor occupancy in narrower spaces. However, G-PCC (Octree) is less effective at compressing dense point clouds than multi-grained approaches (such as G-PCC (Trisoup)), which exploit the continuous point distribution in nodes partitioned by the pruned octree over larger spaces. Therefore, we propose a lossy multi-grained compression with extended octree and dual-model prediction. The extended octree, where each partitioned node contains intra-block and extra-block points, is applied to address poor prediction (such as overfitting) at the node edges of the octree partition. For the points of each multi-grained node, dual-model prediction fits surfaces and projects residuals onto the surfaces, reducing projection residuals for efficient 2D compression and fitting complexity. In addition, a hybrid DWT-DCT transform for 2D projection residuals mitigates the resolution degradation of DWT and the blocking effect of DCT during high compression. Experimental results demonstrate the superior performance of our method over advanced G-PCC (Octree), achieving BD-Rate gains of 55.9% and 45.3% for point-to-point (
D1
) and point-to-plane (
D2
) distortions, respectively. Our approach also outperforms G-PCC (Octree) and G-PCC (Trisoup) in subjective evaluation.
Synthesis and Verification of Mission Plans for Multiple Autonomous Agents under Complex Road Conditions
Authors: Gu Rong , Baranov Eduard , Ameri Afshin , Seceleanu Cristina , Enoiu Eduard Paul , Cürüklü Baran , Legay Axel , Lundqvist Kristina
Published: June 2024

Mission planning for multi-agent autonomous systems aims to generate feasible and optimal mission plans that satisfy given requirements. In this article, we propose a tool-supported mission-planning methodology that combines (i) a path-planning algorithm for synthesizing path plans that are safe in environments with complex road conditions, and (ii) a task-scheduling method for synthesizing task plans that schedule the tasks in the right and fastest order, taking into account the planned paths. The task-scheduling method is based on model checking, which provides means of automatically generating task execution orders that satisfy the requirements and ensure the correctness and efficiency of the plans by construction. We implement our approach in a tool named MALTA, which offers a user-friendly GUI for configuring mission requirements, a module for path planning, an integration with the model checker UPPAAL, and functions for automatic generation of formal models, and parsing of the execution traces of models. Experiments with the tool demonstrate its applicability and performance in various configurations of an industrial case study of an autonomous quarry. We also show the adaptability of our tool by employing it in a special case of an industrial case study.