bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of wild-type vaccine doses on BA.5 hybrid immunity, disease severity, and XBB reinfection risk
Authors: Chen Daxiang , Zhang Weihong , Xiao Bin , Xu Banglao , Yang Xiaoyun , Deng Shidong , Li Guichang , Yang Gang , Cao Jinpeng , Mei Xinyue , Luo Qi , Huang Peiyu , Sun Xi , su Jie , Zhong Nanshan , Zhao Zhuxiang , Wang Zhongfang
Published: November 2024

Vaccination against the wild-type (WT) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus did not produce detectable levels of neutralizing antibodies (NAbs) against the BA.5 strain before it emerged. However, coronavirus disease-2019 (COVID-19) severity varied highly between unvaccinated, partially vaccinated, and fully vaccinated individuals, for unknown reasons. We assessed the severity of BA.5 infection and the risk of XBB strain reinfection and measured serum levels of NAbs against WT, BA.5, and XBB.1.9.1 SARS-CoV-2 strains at varying time points in 1,373 individuals who received zero, one, two, or three WT vaccine doses. We found that two to three WT doses significantly increased WT and BA.5 NAb levels and reduced the incidence of COVID-19-associated pneumonia upon BA.5 strain infection compared to zero to one dose. Regarding XBB reinfection, those who received two to three doses and were infected with the BA.5 variant exhibited a significantly lower reinfection risk compared to those who received zero to one dose. RNA analysis revealed that the differentially expressed genes between the two to three dose and unvaccinated groups were enriched in B cell activation, cytokine-cytokine receptor interaction, complement, and monocyte activation functions—indicating that vaccination increased the antibody response and reduced inflammation. Our results suggest that multiple antigen exposures to either matched or unmatched SARS-COV-2 variants, through vaccination or infection, may be necessary to achieve significant immune imprinting.

IMPORTANCE

The administration of coronavirus disease-2019 (COVID-19) vaccines that do not perfectly match the viral strains that individuals become infected with has been found to impact the resultant illness severity—although the precise mechanism underlying this phenomenon remains unclear. We assessed viral clearance, as well as serum levels of inflammatory cytokines and neutralizing antibodies (NAbs) against wild-type, BA.5, and XBB.1.9.1 variants of the severe acute respiratory syndrome coronavirus 2 among individuals who received varying doses of such strain-mismatched vaccines. Notably, vaccination with ≥2 doses of strain-mismatched COVID-19 vaccines appeared to stimulate the production of specific NAbs during infection with new variants, as well as attenuate the inflammatory response and enhance viral clearance. Such vaccination regimens can also reduce the risk of reinfection. These findings may be important for guiding the development of future COVID-19 vaccination strategies that target both matched and mismatched viral variants.
Age-specific dynamics of neutralizing antibodies, cytokines, and chemokines in response to La Crosse virus infection in mice
Authors: Alatrash Reem , Vaidya Varun , Herrera Bobby Brooke
Published: November 2024

La Crosse virus (LACV) is a primary cause of pediatric arboviral encephalitis in the United States, particularly affecting children aged 16 years or younger. This age-related susceptibility extends to murine models, where weanling mice (3 weeks old) succumb to LACV infection, while adults (≥6 weeks old) demonstrate resistance. Despite its clinical relevance, the host immune response to LACV is not fully understood. In this study, we investigated the roles of neutralizing antibodies (nAbs), cytokines, and chemokines in weanling and adult mice following infection with 5 × 10
5
plaque-forming units (PFU) of LACV. Weanling mice demonstrated early disease onset with elevated peripheral viremia, but passive transfer of adult serum, confirmed to have nAbs, to naïve weanlings prior to infection completely rescued them from death. Moreover, adult mice had increased Th1 cytokines, Th9/Th17/Th22/Treg cytokines, and many chemokines. In contrast, weanlings had higher Th2 cytokines, correlating with symptoms onset. Flow cytometry and intracellular cytokine staining further demonstrated that weanling mice produced higher levels of IL-4 by CD4
+
and CD8
+
T cells compared to adults, regardless of infection status. Conversely, LACV-infected adult mice had increased IFN-γ production by CD8
+
T cells compared to uninfected controls. Finally, the adoptive transfer of splenocytes from immune adult mice to naïve weanlings delayed neurological symptoms and improved survival. In conclusion, this study links nAbs and cytokine and chemokine responses to protective immunity in adult mice, contrasting with the pathogenesis seen in weanlings. These findings underscore the importance of further research into innate and adaptive immune mechanisms during LACV infection.

IMPORTANCE

La Crosse virus (LACV) is a primary cause of pediatric encephalitis in the United States, with an impact on children aged 16 years or younger. This age-related susceptibility is recapitulated in mouse models, where young mice succumb to LACV-induced disease, while adults demonstrate resistance. Our understanding of host responses to LACV remains underexplored. This study sheds light on the dynamics of neutralizing antibodies (nAbs), cytokines, and chemokines following LACV infection in both adult and weanling mice. Our study reveals age-specific variations in viremia, neutralizing antibody titers, survivability, and levels of cytokines and chemokines. Adult mice exhibit significantly elevated levels of Th1 cytokines, contrasting with elevated levels of Th2 cytokines observed in weanling mice, often coinciding with the onset of symptoms. These data reveal age-specific dynamics in cytokines and chemokines associated with protective versus pathogenic immunity, emphasizing the need for further studies on innate and adaptive immunity.
Metagenomic analysis reveals higher
Coriobacteriia
abundance in mare’s milk consumers
Authors: Mukhanbetzhanov Nurislam , Jarmukhanov Zharkyn , Kozhakhmetov Samat , Kushugulova Almagul
Published: November 2024

Our study reveals increased gut
Coriobacteriia
among mare’s milk consumers; metagenomic analysis showed a higher prevalence of genera belonging to class
Coriobacteriia
in consumers vs non-consumers. This suggests interactions between traditional dairy practices and gut microbiome composition, indicating potential for microbiota modulation through dietary interventions.
Cost-effectiveness of psychological and psychosocial interventions for adults, children and young people who have self-harmed
Authors: Mavranezouli Ifigeneia , Pelone Ferruccio , Connolly Rachel , Mughal Faraz , Witt Katrina G , Hawton Keith , Lascelles Karen , Wildgoose Amanda , Childs Angela , Pilling Stephen , Kapur Navneet
Published: November 2024

Background

Self-harm is a major health issue resulting in high societal costs. Few psychological and psychosocial interventions have shown effectiveness in reducing repeat self-harm.

Objective

To assess the cost-effectiveness of psychological and psychosocial interventions that have shown evidence of effectiveness in adults and CYP (children and young people) who have self-harmed.

Methods

Using effectiveness data from Cochrane reviews, we developed two decision-analytical models to compare costs and quality-adjusted life years (QALYs) of cognitive behavioural therapy (CBT)-informed psychological therapy added to treatment as usual (TAU) versus TAU alone for adults who have self-harmed, and of dialectical behavioural therapy for adolescents (DBT-A) versus enhanced TAU for CYP who have self-harmed, respectively, from a National Health Service and personal social services perspective in England. Other model input parameters were obtained from published sources, supplemented by expert opinion.

Findings

The incremental cost-effectiveness ratio (ICER) of CBT-informed psychological therapy added to TAU versus TAU alone for adults who have self-harmed was £9088/QALY. The ICER of DBT-A versus enhanced TAU for CYP who have self-harmed was £268 601/QALY. Results were overall robust to the alternative scenarios tested.

Conclusions and clinical implications

CBT-informed psychological therapy appears to be cost-effective for adults who have self-harmed, which contributes to evidence for its implementation in services. Currently, DBT-A does not seem to be cost-effective for CYP who have self-harmed. The economic analyses were informed by clinical evidence of moderate-to-low (CBT) and low (DBT-A) quality. Further clinical and economic evidence for DBT-A and other psychological and psychosocial interventions for people who have self-harmed is required.
Efficacy of a computer vision-based system for exercise management in patients with knee osteoarthritis: a study protocol for a randomised controlled pilot trial
Authors: Xu Yang , Chen Xi , Wang Li , You Mingke , Deng Qian , Liu Di , Lin Ye , Liu Weizhi , Li Peng-Cheng , Li Jian
Published: November 2024

Introduction

This study aims to evaluate the efficacy of a computer vision system in guiding exercise management for patients with knee osteoarthritis (OA) by comparing functional improvement between a tele-rehabilitation versus an outpatient intervention program.

Methods and analysis

This is a prospective, single-blind, randomised controlled trial of 60 patients with knee OA who will be randomly assigned to exercise therapy (n=30) or control (n=30) . Both groups will receive treatment two times per week for 12 weeks. The primary outcome of the study will be assessed using the University of Western Ontario and McMaster University Osteoarthritis Index (WOMAC). The Knee Injury and Osteoarthritis Outcome Score will be assessed, as well as the visual analogue scale, quality of life score and physical fitness score. All observations will be collected at baseline and at weeks 4, 8 and 12 during the intervention period, as well as at weeks 4, 8, 12 and 24 during the follow-up visits after the end of the intervention.

Ethics and dissemination

This evaluator-blinded, prospective, randomised controlled study was approved by the Biomedical Ethics Review Committee of West China Hospital of Sichuan University.

Trial registration number

ChiCTR2300070319.
Patient-reported harm following cancellation of planned surgery at a Danish university hospital: a cross-sectional study
Authors: Viftrup Anette , Laustsen Sussie , Pahle Maria Levin , Dreyer Pia , Nikolajsen Lone
Published: November 2024

Objectives

To estimate the prevalence and severity of patient-reported physical and non-physical harm following surgery cancellation.

Design

Cross-sectional study.

Setting

A large Danish university hospital.

Participants

Patients (≥18 years) from various surgical specialities, such as orthopaedic, spinal, abdominal, gynaecological, thoracic, vascular and urological surgery whose surgery was cancelled <2 weeks prior to the scheduled date due to hospital-related causes.

Outcome

Patient-reported physical and non-physical harm, defined as physical worsening, emotional strain and other consequences, measured using a patient-reported survey.

Results

We identified 785 patients whose surgery was cancelled from 1 December 2021 to 1 June 2022, of whom 436 (55.5%) responded to the electronic survey. Physical worsening was reported by 42% and emotional strain by 48% of patients. One-third of patients reported an inability to continue daily activities, and 28% reported a need for an increased dose of analgesics. Emotional strain included various negative feelings such as being disappointed (59%) and lonely (31%). Furthermore, 44% of the respondents feared deterioration of their disease and 9% experienced anxiety of dying. The relative risk of emotional strain was higher in females than in males (54% vs 41%, adjusted relative risk (RR)=1.32 (1.08; 1.63)). A waiting period >30 days compared with ≤30 days was associated with a higher risk of physical worsening (25.3% vs 48.9%, adjusted RR=1.93 (1.42; 2.63)).

Conclusions

Harm, measured as physical worsening and emotional strain, is reported with severity by nearly half of respondents following cancellation.
Scoping review of enablers and challenges of implementing pharmacogenomics testing in the primary care settings
Authors: Mai Chun-Wai , Sridhar Sathvik B , Karattuthodi Mohammed Salim , Ganesan Perishithaa M , Shareef Javedh , Lee E Lyn , Armani Keivan
Published: November 2024

Introduction

Pharmacogenomic testing (PGx) plays a crucial role in improving patient medication safety, yet ethical concerns and limitations impede its clinical implementation in the primary care settings.

Aims

To systematically review the current state of PGx in the primary care settings and determine the enablers and challenges of its implementation.

Design

A scoping review was carried out by adhering to Arksey and O’Malley’s 6-stage methodological framework and the 2020 Joanna Briggs Institute and Levacet al.

Data sources

Cochrane Library, EMBASE, Global Health, MEDLINE and PubMed were searched up to 17 July 2023.

Eligibility criteria

All peer-reviewed studies in English, reporting the enablers and the challenges of implementing PGx in the primary care settings were included.

Date extraction and synthesis

Two independent reviewers extracted the data. Information was synthesised based on the reported enablers and the challenges of implementing PGx testing in the primary care settings. Information was then presented to stakeholders for their inputs.

Results

78 studies discussing the implementation of PGx testing are included, of which 57% were published between 2019 and 2023. 68% of the studies discussed PGx testing in the primary care setting as a disease-specific themes. Healthcare professionals were the major stakeholders, with primary care physicians (55%) being the most represented. Enablers encompassed various advantages such as diagnostic and therapeutic benefits, cost reduction and the empowerment of healthcare professionals. Challenges included the absence of sufficient scientific evidence, insufficient training for healthcare professionals, ethical and legal aspects of PGx data, low patient awareness and acceptance and the high costs linked to PGx testing.

Conclusion

PGx testing integration in primary care requires increased consumer awareness, comprehensive healthcare provider training on legal and ethical aspects and global feasibility studies to better understand its implementation challenges. Managing high costs entails streamlining processes, advocating for reimbursement policies and investing in research on innovation and affordability research to improve life expectancy.
Early Hearing Detection and Intervention programmes for neonates, infants and children in non-Asian low-income and middle-income countries: a systematic review
Authors: Rajanbabu Keerthana , Joshi B Deepashree , Ramkumar Vidya , Kuper Hannah , Vaidyanath Ramya
Published: November 2024

Introduction

Early Hearing Detection and Intervention (EHDI) programmes were established to reduce the impact of hearing loss on children. High-income countries (HICs) have resources and knowledge to execute these programmes. However, financial and other resource constraints limit the availability of these programmes to low-income and middle-income countries (LMICs). Yet, LMICs have explored strategies to implement EHDI programmes in their context; the outcomes are still largely unknown.

The aim of this study is to identify the various models of the EHDI program implemented in non-Asian LMICs.

Aim

Method

Studies published between 2010 and 2023 reporting EHDI programmes in non-Asian LMICs for children were considered. The primary databases searched were PubMed, Scopus, Web of Science, EBSCOHost, EBSCO-CINAHL and ProQuest dissertations. The search results are summarised using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses chart. Quality appraisal and risk-of-bias assessment were assessed. Using the retrieved data, a narrative synthesis of the identified methods and forest plots for the prevalence estimate was created.

Results

Fifty-six studies from 16 LMICs were included. They were grouped into 29 hearing screening programmes for neonates and infants and 26 programmes for older children. Predominantly hospital-based screening was employed for neonates and infants and school-based screening for older children. Two-stage otoacoustic emissions screening was employed for neonates and infants, while single-stage pure tone audiometry with otoscopy screening was used for older children. Predominantly, audiologists performed screening and diagnostics for neonates/infants while community health workers performed screening for the older children. Screening aspects were reported predominantly and not diagnostic evaluation/intervention outcomes. Overall, the economics of EHDI was reported only anecdotally in a few studies.

Conclusion

The screening strategies were not uniform among non-Asian LMICs. The protocols used were similar to HICs, yet few developed protocols adapting the Joint Committee of Infant Hearing. However, long-term outcomes such as rate of identification, suitable intervention and their outcomes are not known. EHDI programmes with successful outcomes of early intervention must be studied and reported with economic evaluations.
Attitudes towards the regulation and provision of abortion among healthcare professionals in Britain: cross-sectional survey data from the SACHA Study
Authors: Wellings Kaye , Scott Rachel H , Sheldon Sally , McCarthy Ona , Palmer Melissa J , Shawe Jill , Meiksin Rebecca , Lewandowska Maria , Cameron Sharon T , Reiter Jennifer , French Rebecca S
Published: November 2024

Objectives

To gather views of healthcare professionals on the regulation and provision of abortion in Britain.

Methods

Cross-sectional, stratified cluster sample survey of healthcare professionals working in a range of healthcare services including abortion services. Measures included knowledge of and attitudes towards the regulation and provision of abortion.

Results

A total of 771 healthcare professionals responded. More than nine in ten supported abortion being a woman’s choice and a clear majority favoured abortion being treated as a health rather than a legal issue. Some 6.2% saw abortion at any gestational age as contrary to personal beliefs and a similarly small minority (6.7%) opposed abortion after 12 weeks’ gestation. One in five of all healthcare professionals and a third of those aged under 30 years were unaware that the law in Britain requires two doctors to authorise an abortion. Free-text comments revealed opposition to the need for this legal requirement. Support for an extended role for nurses in abortion care was high; 65.3% agreed that nurses should be able to prescribe abortion medication. Little more than a third of all healthcare professionals (37.0%) agreed that abortion should be standard practice in their service; the proportion was highest among those in sexual and reproductive health services (58.4%) and lowest among those in general practice (18.7%).

Conclusions

Healthcare professionals in Britain were generally supportive of abortion being treated in the same way as other health issues and would be likely to support any moves to decriminalise abortion.
Intratumoral and peritumoral radiomics of MRIs predicts pathologic complete response to neoadjuvant chemoimmunotherapy in patients with head and neck squamous cell carcinoma
Authors: Lin Peiliang , Xie Wenqian , Li Yong , Zhang Chenjia , Wu Huiqian , Wan Huan , Gao Ming , Liang Faya , Han Ping , Chen Renhui , Cheng Gui , Liu Xuekui , Fan Song , Huang Xiaoming
Published: November 2024

Background

For patients with locally advanced head and neck squamous cell carcinoma (HNSCC), combined programmed death receptor-1 inhibitor and chemotherapy improved response rate to neoadjuvant therapy. However, treatment response varies among patients. There is no tool to predict pathologic complete response (pCR) with high accuracy for now. To develop a tool based on radiomics features of MRI to predict pCR to neoadjuvant chemoimmunotherapy (NACI) may provide valuable assistance in treatment regimen determination for HNSCC.

Methods

From January 2021 to April 2024, a total of 172 patients with HNSCC from three medical center, who received NACI followed by surgery, were included and allocated into a training set (n=84), an internal validation set (n=37) and an external validation set (n=51). Radiomics features were extracted from intratumoral and different peritumoral areas, and radiomics signature (Rad-score) for each area was constructed. A radiomics-clinical nomogram was developed based on Rad-scores and clinicopathological characteristics, tested in the validation sets, and compared with clinical nomogram and combined positive score (CPS) in predicting pCR.

Results

The radiomics-clinical nomogram, incorporating peritumoral Rad-score, intratumoral Rad-score and CPS, achieved the highest accuracy with areas under the receiver operating characteristic curve of 0.904 (95% CI, 0.835 to 0.972) in the training cohort, 0.860 (95% CI, 0.722 to 0.998) in the internal validation cohort, and 0.849 (95% CI, 0.739 to 0.959) in the external validation cohort, respectively, which outperformed the clinical nomogram and CPS in predict pCR to NACI for HNSCC.

Conclusion

A nomogram developed based on intratumoral and peritumoral MRI radiomics features outperformed CPS, a widely employed biomarker, in predict pCR to NACI for HNSCC, which would provide incremental value in treatment regimen determination.
Role ofCD47gene expression in colorectal cancer: a comprehensive molecular profiling study
Authors: Arai Hiroyuki , Gandhi Nishant , Battaglin Francesca , Wang Jingyuan , Algaze Sandra , Jayachandran Priya , Soni Shivani , Zhang Wu , Yang Yan , Millstein Joshua , Lo Jae Ho , Sohal Davendra , Goldberg Richard , Hall Michael J , Scott Aaron James , Hwang Jimmy J , Lou Emil , Weinberg Benjamin A , Marshall John , Goel Sanjay , Xiu Joanne , Korn W Michael , Lenz Heinz-Josef
Published: November 2024

Background

In patients with colorectal cancer (CRC), the therapeutic effects of conventional immune checkpoint inhibitors targeting the adaptive immune system are largely limited to those with microsatellite instability-high tumors. Meanwhile, new immunotherapies targeting the innate immune system are attracting increasing attention. CD47 is a representative innate immune checkpoint involved in the evasion of tumor cell phagocytosis by macrophages. This large-scale study comprehensively examined the molecular significance ofCD47gene expression in CRC.

Methods

We analyzed the next-generation sequencing data of DNA and RNA from 14,287 CRC cases included in the data set of a commercial Clinical Laboratory Improvement Amendments-certified laboratory (Caris Life Sciences). The cases were divided into two groups based on the median value ofCD47gene expression levels. The molecular and immune profiles between the groups were compared, and the relationship betweenCD47expression and survival outcomes was further examined.

Results

InCD47-high tumors, the proportion of consensus molecular subtypes 1 and 4 was significantly higher than inCD47-low tumors. The expression levels of damage-associated molecular pattern-related genes showed a positive correlation withCD47expression levels. Major oncogenic pathways, such as mitogen-activated protein kinase, phosphoinositide 3-kinase, angiogenesis, and transforming growth factor beta, were significantly activated inCD47-high tumors. Additionally, the expression levels of a panel of adaptive immune checkpoint genes and estimates of immune cells constituting the tumor microenvironment (TME) were significantly higher inCD47-high tumors.

Conclusions

CD47expression in CRC was associated with the activation of several oncogenic pathways and an immune-engaged TME. Our findings may provide valuable information for considering new therapeutic strategies targeting innate immune checkpoints in CRC.
WWOX tuning of oleic acid signaling orchestrates immunosuppressive macrophage polarization and sensitizes hepatocellular carcinoma to immunotherapy
Authors: Liu Shaoqing , Yang Shiguang , Xu Min , Zhou Qiang , Weng Jialei , Hu Zhiqiu , Xu Minghao , Xu Wenxin , Yi Yong , Shi Yi , Dong Qiongzhu , Hung Mien-Chie , Ren Ning , Zhou Chenhao
Published: November 2024

Background

Immune checkpoint inhibitors (ICIs) are therapeutically effective for hepatocellular carcinoma (HCC) but are individually selective. This study examined the role of specific common fragile sites (CFSs) related gene in HCC immunotherapy.

Methods

We analyzed HCC tissues using next-generation sequencing and flow cytometry via time-of-flight technology. A humanized orthotopic HCC mouse model, an in vitro co-culture system, untargeted metabolomics and a DNA pulldown assay were used to examine the function and mechanism of WWOX in the tumor immune response.

Results

WWOX was the most upregulated CFS-related gene in HCC patients responsive to ICIs. WWOX deficiency renders HCC resistant to PD-1 treatment in humanized orthotopic HCC mouse model. Macrophage infiltration is increased and CD8 T-cell subset infiltration is decreased in WWOX-deficient HCC patients. HCC-derived oleic acid (OA) promotes macrophage conversion to an immunosuppressive phenotype. Mechanistically, WWOX deficiency promoted OA synthesis primarily via competitive binding of NME2 with KAT1, which promoted acetylation of NME2 at site 31 and inhibited NME2 binding to the SCD5 promoter region. Pharmacological blockade of SCD5 enhanced the antitumor effects of anti-PD-1 therapy.

Conclusions

WWOX is a key factor for immune escape in HCC patients, which suggests its use as a biomarker for stratified treatment with ICIs in clinical HCC patients.
Heterozygous de novo variants inHSPD1cause hypomyelinating leukodystrophy through impaired HSP60 oligomerisation
Authors: Eskin-Schwartz Marina , Seraidy Shaikah , Paz Eyal , Molhem Maism , Ranza Emmanuelle , Antonarakis Stylianos E , Blanc Xavier , Herman Kristin , Benko William S , Libzon Stephanie , Ben Sira Liat , Fattal-Valevski Aviva , Dolgin Vadim , Birk Ohad S , Kessel Amit , Bross Peter , Weiss Celeste , Azem Abdussalam , Zerem Ayelet
Published: November 2024

Introduction

Hypomyelinating leukodystrophies are a group of genetic disorders, characterised by severe permanent myelin deficiency. Their clinical features include developmental delay with or without neuroregression, nystagmus, central hypotonia, progressing to spasticity and ataxia.HSPD1encodes the HSP60 chaperonin protein, mediating ATP-dependent folding of imported proteins in the mitochondrial matrix. Pathogenic variants inHSPD1have been related to a number of neurological phenotypes, including the dominantly inherited pure hereditary spastic paraplegia (MIM 605280) and the recessively inherited hypomyelinating leukodystrophy 4 (MIM 612233). Subsequently, an additional phenotype of hypomyelinating leukodystrophy has been reported due to de novo heterozygousHSPD1variants.

In the current work, we expand the clinical and genetic spectrum of this hypomyelinating disorder by describing a cohort of three patients, being heterozygous forHSPD1variants involving residue Ala536 of HSP60 (the novel p.Ala536Pro variant and the previously reported p.Ala536Val).

Methods

Clinical and radiological evaluation; whole exome sequencing, in vitro reconstitution assay and patient fibroblast cell lysate analysis.

Results

Clinical manifestation was of early-onset nystagmus, tremor and hypotonia evolving into spasticity and ataxia and childhood-onset neuroregression in one case. Brain MRI studies revealed diffuse hypomyelination.

The 3D protein structure showed these variants to lie in spatial proximity to the previously reported Leu47Val variant, associated with a similar clinical phenotype. In vitro reconstitution assay and patient fibroblast cell lysate analysis demonstrated that these mutants display aberrant chaperonin protein complex assembly.

Discussion

We provide evidence that impaired oligomerisation of the chaperonin complex might underlie this HSPD1-related phenotype, possibly through exerting a dominant negative effect.
Varicella zoster vasculopathy causing recurrent ischaemic strokes in an immunocompetent patient
Authors: Barreau Ariana , Lu Jeffrey , Weis Blake , Mikhail Fadi
Published: November 2024

A 66-year-old woman reported 10 days of generalised weakness, falls and memory ‘glitches’. She had developed left-sided ophthalmic herpes zoster 3 months before but was otherwise well. MR scan of brain showed acute left-sided ischaemic strokes and CT cerebral angiogram identified marked stenoses of the left anterior and middle cerebral arteries. We suspected varicella-zoster virus vasculopathy, confirmed by cerebrospinal fluid analysis. Initially she had further ischaemic strokes despite intravenous acyclovir, prednisone, aspirin and clopidogrel. However, after prolonged acyclovir and prednisone, there were no new infarcts though imaging of left anterior and middle cerebral artery vessel walls showed persistent inflammation. Varicella zoster vasculopathy can cause recurrent ischaemic strokes, even in immunocompetent people with no cardiovascular risk factors, and despite long-term antiviral therapy.
Field performance of asphalt mixture modified with reactive isocyanate-based modifier
Authors: Tran Nam H. , Moraes Raquel , Taylor Adam , Timm David
Published: November 2024

The reactive isocyanate-based modifier chemically reacts with asphalt components. This chemical reaction helps overcome the issues of increased viscosity and phase separation encountered with conventional modified binders. The reactive isocyanate-based modifier can be used by itself or with other modifiers and additives to modify binders to meet the highest performance grades currently specified by state highway agencies. This project aimed to demonstrate the constructability of an asphalt mixture modified with the reactive isocyanate-based modifier in the field and compare its performance with that of a control mixture. The project involved milling an approximately 5.0 cm (2 in.) thick surface layer of two 30.5 m (100 ft) sections with similar foundation support. One section was resurfaced with a reactive isocyanate-modified mixture and the other with a conventional styrene-butadiene-styrene-modified mix. The mixtures have shown no significant difference in field performance and laboratory performance test results. This study has provided insights into the field applicability of reactive isocyanate-based modifiers in asphalt mixtures, facilitating the ongoing efforts to develop durable road surfaces.
New constraints on the timing and nature of metamorphism in the eastern Meguma terrane, Nova Scotia, Canada
Authors: van Rooyen Deanne , Archibald Donnelly B. , White Chris E. , Everest Rachel L. , Ross Colin G. , Smit Matthijs A.
Published: November 2024

The Meguma terrane in Nova Scotia consists mainly of Cambrian to Ordovician metasedimentary rocks intruded by abundant peraluminous granite, granodiorite, and minor diorite–tonalite–plutons between ca. 380 and 360 Ma. The metasedimentary rocks were variably metamorphosed to greenschist- to amphibolite-facies during the Early Devonian. In the eastern Meguma terrane, the regional M1 chlorite- and biotite-zone assemblages are overprinted by two types of high-temperature low-pressure M2 metamorphism. In contact aureoles around plutons the regional M1 assemblages are overprinted by cordierite- and andalusite-bearing M2 contact metamorphic assemblages, and away from plutons chlorite-bearing, (or biotite-bearing) regional M1 assemblages are overprinted by staurolite-, garnet-, and (or) cordierite-bearing M2 regional assemblages that represent metamorphism driven by a regional elevated thermal gradient. The interpreted metamorphic conditions in the eastern Meguma terrane range from ca. 480–550 °C and pressures below 2.5 kbar up to 550–650 °C with pressures between 4 and 5 kbar. Based on a new garnet Lu–Hf age, regional metamorphism was ongoing at ca. 372 Ma, hence broadly coeval with pluton emplacement. Metamorphism and pluton emplacement took place in a largely transpressional tectonic setting during the collision of the Meguma terrane with Avalonia. After pluton emplacement, peak metamorphic assemblages were variably overprinted with retrograde chlorite and sericite M3 assemblages while deformation continued. Regional structures were transposed into a composite transposition foliation as a result of continued motion along the terrane-bounding Minas Fault Zone and associated ductile shear zones.
Generation of phonon quantum states and quantum correlations among single photon emitters in hexagonal boron nitride
Authors: Molinares Hugo , Pinilla Fernanda , Muñoz Enrique , Muñoz Francisco , Eremeev Vitalie
Published: November 2024

Hexagonal boron nitride exhibits two types of defects with great potential for quantum information technologies: single-photon emitters (SPEs) and one-dimensional grain boundaries hosting topologically-protected phonons, termed as topologically-protected phonon lines (TPL). Here, by means of a simple effective model and density functional theory calculations, we show that it is possible to use these phonons for the transmission of information. Particularly, a single SPE can be used to induce single-, two- and qubit-phonon states in the one-dimensional channel, and (ii) two distant SPEs can be coupled by the TPL that acts as a waveguide, thus exhibiting strong quantum correlations. We highlight the possibilities offered by this material-built-in nano-architecture as a phononic device for quantum information technologies.
A Geometric Numerical Integration with Simple Cell Mapping for Global Analysis of Nonlinear Dynamical Systems
Authors: Huang Fei-Long , Chen Li-Qun , Jiang Wen-An
Published: November 2024

In order to improve the efficiency in computing the global properties of nonlinear systems, some effective methods have been proposed for the global analysis of these systems. However, there are only few investigations focusing on the numerical algorithms of the system response trajectories. This paper presents a higher-efficiency geometric numerical integration method with simple cell mapping for solving the basins of attraction of nonlinear systems. This numerical algorithm is based on the rule of Lie derivative, using it to calculate the trajectories of the nonlinear systems. Then, the global structure is studied by the numerical algorithm associated with a simple cell mapping method. Compared with the traditional Runge–Kutta methods of orders 4 and 5, it is demonstrated that the proposed Lie derivative iterative algorithm has significant advantages in efficiency.
The Cretaceous World
Authors: Hart Malcolm B. , Batenburg Sietske J. , Huber Brian T. , Price Gregory D. , Thibault Nicolas , Wagreich Michael , Walaszczyk Irek P.
Published: November 2024

The Cretaceous System was first established by Jean Baptiste Julien d'Omalius d'Halloy based on his geological mapping of France and the adjacent areas of the Low Countries and Northern Italy. His map, which was published in 1822, has a legend with a rock unit identified as ‘
Terrain Crétacé
’, and that was the birth of the Cretaceous System that we still use today. Unlike many of the other geological systems, there was no definitive publication. The Cretaceous, as currently defined, occupies the interval of time from 145 to 66 Ma, making it one of the longest in the Phanerozoic. The Cretaceous includes both icehouse and greenhouse (even hothouse) conditions, and much of the time is characterized by exceptionally high sea levels.
Seismic stratigraphic units, palaeogeography and their effect on hydrocarbon distribution in the upper Neogene of the Pannonian Basin
Authors: Árgyelán Gizella Bagoly , Zadravecz Csilla , Nyiri Dániel , Magyar Imre
Published: November 2024

The upper Neogene lacustrine sedimentary succession of the Pannonian Basin in Hungary was divided into 40 sequences (clinothems) by seismic stratigraphic methods. The geographic position of the clinothems reflects the gradual infilling of the basin. Different patterns of progradation, aggradation and retrogradation can be observed within the same clinothem sets along the northern shelf of Lake Pannon, demonstrating that lake level was controlled by local factors, such as tectonics and sediment supply, not solely by climate. The distribution of discovered hydrocarbon resources within the clinothems by time, by depositional environment and by geographical regions was investigated for the first time through a systematic reservoir-level analysis. The reservoir sands are increasingly younger from the northwest towards the southeast, following the progradation of the shelf. Within each region, the oldest reservoir layers appear in the deep basin, whereas the second or third reservoir peaks are associated with deltaic environments. There appear to have been no general time intervals with basin-wide reservoir peaks when sands in anomalously large quantity or with specifically good reservoir quality were deposited. The petroleum accumulation was influenced by local factors in each sub-basin, such as inherited structure, syn- and post-sedimentary deformation, sediment source and maturity, and topographic confinement.
Full-body impressions: a category of trace fossils unique to exceptionally preserved bedding planes and indicators of true substrates
Authors: Benner Jacob S. , Knecht Richard J.
Published: November 2024

Certain biogenic sedimentary structures can be considered to be reliable indicators of true substrates. Full-body impressions, or FBIs, are trace fossils that are shallow, highly detailed impressions of the ventral axial anatomy of low body mass animals
made while living
. Their mode of preservation makes FBIs distinct from undertracks, body moulds or passive tool marks. FBIs are made at the air– or water–substrate interface during sedimentary stasis. Associated trace fossils, like those that exhibit excavations with preserved waste mounds and very near-surface burrow roofs, located on the same bedding plane, can support the interpretation of true substrate preservation. Integration of the biogenic and sedimentological data from both Carboniferous and Pleistocene sites with well-preserved bedding-plane trace fossil assemblages has confirmed the conditions under which true substrates are preserved. These include periods (as brief as days to weeks) of sedimentary stasis, followed by gentle deposition without erosion, and without the need to invoke biofilms or biomats as consolidants. The potential for these taphonomic conditions exists in both alluvial and lacustrine environments, as well as intertidal-estuarine valleys, as described by other published examples of FBI preservation. Future FBI discoveries will prove useful in identifying true substrates across a range of time periods and environments.
CroCoDai
: A Stablecoin for Cross-Chain Commerce
Authors: Reijsbergen Daniël , Hajek Bretislav , Dinh Tien Tuan Anh , Keppo Jussi , Korth Henry F. , Datta Anwitaman
Published: November 2024

Decentralized Finance (DeFi), in which digital assets are exchanged without trusted intermediaries, has grown rapidly in value in recent years.
Stablecoins
, which are pegged to a non-volatile asset such as the US dollar, are a prominent feature of DeFi as they mitigate the risk associated with price fluctuations. However, existing stablecoin systems are tied to individual blockchain platforms, and trusted parties or complex protocols are needed to exchange stablecoin tokens between blockchains. Our goal is to design a practical stablecoin system for cross-chain commerce, and to do so we must overcome two main challenges. The first is to support a large and growing number of blockchains efficiently. The second is for the stablecoin to be resilient to blockchain platform failures and to price fluctuations that affect its collateral. We present
CroCoDai
to address these challenges. We demonstrate
CroCoDai
's efficiency by comparing the performance of a prototype implementation to related baselines, and its resilience through an empirical analysis of historical token price data.
TEC-CNN: Toward Efficient Compressing of Convolutional Neural Nets with Low-rank Tensor Decomposition
Authors: Wang Yifan , Feng Liang , Cai Fenglin , Li Lusi , Wu Rui , Li Jie
Published: November 2024

Most state-of-the-art convolutional neural networks (CNNs) are characterized by excessive parameterization, leading to a high computational burden. Tensor decomposition has emerged as a model reduction technique for compressing deep neural networks. Previous approaches have predominantly relied on either Tucker decomposition or Canonical Polyadic (CP) decomposition for CNNs. However, CP decomposition exhibits exceptional compression capabilities in comparison to Tucker decomposition, which results in a more pronounced accuracy loss. This article introduces an efficient model compression method, termed TEC-CNN, designed to achieve significant compression while preserving accuracy levels comparable to those of the original models. In TEC-CNN, convolutional layers are identified to obtain convolutional kernels by analyzing given models under the principles of low-rank tensor decomposition, and then, calculating the ranks of convolutional kernels. Furthermore, an efficient decomposition schema for the convolutional kernel is proposed with approximate kernel tensor for reducing parameters. Additionally, a novel format of a convolutional sequence is presented and constructed with a reduced number of parameters to replace the original convolutional layers. Finally, the effectiveness of TEC-CNN is assessed across a range of computer vision tasks. For instance, in CIFAR-100 classification, ResNet18 is compressed to 4.1 MB, while Unext, when applied to image segmentation using the International Skin Imaging Collaboration (ISIC) dataset, is reduced to 3.419 MB. When employed for fire object detection with Yolov7, TEC-CNN achieves a model size reduction of 71.6 MB. Comprehensive experimental results underscore that our approach achieves significant model compression while preserving model performance.
Non-Linear Software Documentation with Interactive Code Examples
Authors: Nassif Mathieu , Robillard Martin P.
Published: November 2024

Documentation enables sharing knowledge between the developers of a technology and its users. Creating quality documents, however, is challenging: Documents must satisfy the needs of a large audience without being overwhelming for individuals. We address this challenge with a new document format named Casdoc. Casdoc documents are interactive resources centered around code examples for programmers. Explanations of the code elements are presented as annotations that the readers reveal based on their needs. We evaluated Casdoc in a field study with over 300 participants who used 126 documents as part of a software design course. During the study, the majority of participants adopted Casdoc instead of a baseline format and used interactive annotations to reveal additional information about the code example. Although participants collectively viewed the majority of the documents’ content, they individually revealed a minority of the annotations they saw. We gathered insights into five aspects of Casdoc that can be applied to other formats and highlighted five lessons learned to improve navigability in online documents.
Identifying Performance Issues in Cloud Service Systems Based on Relational-Temporal Features
Authors: Gu Wenwei , Liu Jinyang , Chen Zhuangbin , Zhang Jianping , Su Yuxin , Gu Jiazhen , Feng Cong , Yang Zengyin , Yang Yongqiang , Lyu Michael R.
Published: November 2024

Cloud systems, typically comprised of various components (e.g., microservices), are susceptible to performance issues, which may cause service-level agreement violations and financial losses. Identifying performance issues is thus of paramount importance for cloud vendors. In current practice, crucial metrics, i.e., Key Performance Indicators (KPIs), are monitored periodically to provide insight into the operational status of components. Identifying performance issues is often formulated as an anomaly detection problem, which is tackled by analyzing each metric independently. However, this approach overlooks the complex dependencies existing among cloud components. Some graph neural network-based methods take both temporal and relational information into account; however, the correlation violations in the metrics that serve as indicators of underlying performance issues are difficult for them to identify. Furthermore, a large volume of components in a cloud system results in a vast array of noisy metrics. This complexity renders it impractical for engineers to fully comprehend the correlations, making it challenging to identify performance issues accurately. To address these limitations, we propose Identifying Performance Issues based on Relational-Temporal Features (ISOLATE), a learning-based approach that leverages both the relational and temporal features of metrics to identify performance issues. In particular, it adopts a graph neural network with attention to characterizing the relations among metrics and extracts long-term and multi-scale temporal patterns using a GRU and a convolution network, respectively. The learned graph attention weights can be further used to localize the correlation-violated metrics. Moreover, to relieve the impact of noisy data, ISOLATE utilizes a Positive Unlabeled (PU) Learning strategy that tags pseudo-labels based on a small portion of confirmed negative examples. Extensive evaluation on both public and industrial datasets shows that ISOLATE outperforms all baseline models with 0.945 F1 score and 0.920 Hit rate@3. The ablation study also proves the effectiveness of the relational-temporal features and the PU-Learning strategy. Furthermore, we share the success stories of leveraging ISOLATE to identify performance issues in Huawei Cloud, which demonstrates its superiority in practice.
SAMControl: Controlling Pose and Object for Image Editing with Soft Attention Mask
Authors: Zhang Yue , Wang Chao , Fang Feifei , Zhuge Yunzhi , Fan Hehe , Chang Xiaojun , Deng Cheng , Yang Yi
Published: November 2024

To achieve content-consistent results in text-conditioned image editing, existing methods typically employ a
reconstruction branch
to capture the source image details via diffusion inversion and a
generation branch
to synthesize the target image based on the given textual prompt and the masked source image details. However, accurately segmenting source details is challenging with the current fixed-threshold mask strategy. Additionally, the inadequacies in the inversion process can lead to insufficient retention of source details. In this paper, we propose a method called SAMControl (
S
oft
A
ttention
M
ask) to adaptively control the pose and object details for image editing. SAMControl dynamically learns flexible attention masks for different images at various diffusion steps. Furthermore, in the reconstruction branch, we utilize a direct inversion technique to ensure the fidelity of source details within SAM. Extensive qualitative and quantitative results demonstrate the effectiveness of the proposed method.