bluuebunny/crossref_metadata_2025 huggingface dataset:
Synovial Sarcoma Chromatin Dynamics Reveal a Continuum in SS18:SSX Reprograming
Authors: Hofvander Jakob , Qiu Alvin , Lee Kiera , Bilenky Misha , Carles Annaïck , Cao Qi , Moksa Michelle , Steif Jonathan , Su Edmund , Sotiriou Afroditi , Goytain Angela , Hill Lesley A. , Singer Sam , Andrulis Irene L. , Wunder Jay S. , Mertens Fredrik , Banito Ana , Jones Kevin B. , Underhill T. Michael , Nielsen Torsten O. , Hirst Martin
Published: May 2024

Synovial sarcoma (SyS) is an aggressive soft-tissue malignancy characterized by a pathognomonic chromosomal translocation leading to the formation of the SS18::SSX fusion oncoprotein. SS18::SSX associates with mammalian BAF complexes suggesting deregulation of chromatin architecture as the oncogenic driver in this tumour type. To examine the epigenomic state of SyS we performed comprehensive multi-omics analysis on 52 primary pre-treatment human SyS tumours. Our analysis revealed a continuum of epigenomic states across the cohort at fusion target genes independent of rare somatic genetic lesions. We identify cell-of-origin signatures defined by enhancer states and reveal unexpected relationships between H2AK119Ub1 and active marks. The number of bivalent promoters, dually marked by the repressive H3K27me3 and activating H3K4me3 marks, has strong prognostic value and outperforms tumor grade in predicting patient outcome. Finally, we identify SyS defining epigenomic features including H3K4me3 expansion associated with striking promoter DNA hypomethylation in which SyS displays the lowest mean methylation level of any sarcoma subtype. We explore these distinctive features as potential vulnerabilities in SyS and identify H3K4me3 inhibition as a promising therapeutic strategy.
Identifying the practice patterns of optometrists in providing falls prevention management: A mixed-methods systematic review protocol
Authors: Lee Si Ye , Alam Khyber , Charng Jason , Niyazmand Hamed , Chen Jingyi , Hill Anne-Marie
Published: May 2024

Objective

The objective of this systematic review is to synthesise the best available evidence for optometrists’ practice patterns in providing falls prevention management.

Introduction

Falls remain the main cause of injury-related hospitalisation and mortality in Australia and worldwide, significantly affecting older adults. The increased risk of comorbidities, including visual impairment in this cohort is linked to a higher incidence of falls. Despite being primary eye care practitioners, community optometrists may not consistently integrate falls prevention strategies into their practice. Furthermore, the extent to which they adhere to evidence-based recommendations for falls management remains unclear.

Inclusion criteria

The review will include optometrists, in regions where optometry is a regulated profession, and report their understanding and practice patterns in delivering falls prevention management to older community-dwelling adults. Qualitative, quantitative, and mixed methods studies will be eligible for inclusion. It is envisioned that most studies will be qualitative. Studies published in English and those published from 1980 onwards will be eligible for inclusion since published evidence for falls prevention began to increase sharply around this time.

Methods

The review will follow the JBI guidelines for mixed methods systematic reviews and will be developed and reported in accordance with PRISMA-P guidelines. Databases that will be searched are Excerpta Medica Database (Embase), Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Complete, and OVID MEDLINE. Grey literature will be searched through Conference Proceedings Citation Index (Web of Science), Google Scholar, and ProQuest Dissertations databases. Two reviewers will independently conduct all screening and critical appraisal. The reviewers will screen all articles’ titles and abstracts retrieved from the searches to determine potential eligibility. All full-text articles considered relevant will then be assessed for final eligibility for inclusion. The final included articles will be assessed for methodological rigour using the JBI SUMARI critical appraisal tools, subsequently, all relevant data will be extracted. Discrepancies at any stage of the procedures will be resolved through discussion and consensus with a third senior researcher. A convergent integrated approach to synthesising and integrating the quantitative and qualitative data will be followed.

Review registration CRD42024539668
The clinical and molecular landscape of breast cancer in women of African and South Asian ancestry
Authors: Thorn GJ , Gadaleta E , Dayem Ullah AZM , James LGE , Abdollahyan M , Barrow-McGee R , Jones JL , Chelala C
Published: May 2024

Our study evaluates the molecular and clinical effects of genetic ancestry in African and South Asian women compared to European using a combined cohort of 7,253 breast cancer patients available from four data sources: the 100,000 Genomes Project (UK), The Cancer Genome Atlas (US), the Breast Cancer Now Biobank (UK) and Genes & Health (UK).

We find that non-European breast cancer patients present significantly earlier and die at a younger age. The African ancestry group has an increased prevalence of higher grade and hormone receptor negative disease. The South Asian group shows tendency towards lower stage at diagnosis and lower tumour mutational burden. We observe significant differences and similarities in the somatic mutational landscape. We identify differences in germline mutation rates in genes used in genetic testing and others implicated in breast cancer predisposition. Potential therapeutic targets are differentially mutated. We report a higher propensity for homologous recombination deficiency serving as a potential therapy response indicator.

Although precision oncology holds the promise of revolutionising healthcare, it could exacerbate the disparities it seeks to eradicate unless research biases are addressed. We harness multimodal data to improve our understanding of ancestry-associated differences in breast cancer and highlight opportunities to advance health equity.
Insights into Hypertension: Microbial Load, Salivary Cytokine Levels and Salivary Flow in Edentulous Patients With Complete Dentures: a Case-Control Study
Authors: Gonçalves Pizziolo Pillar , Clemente Lorena Mosconi , Ribeiro Aline Barbosa , Oliveira Viviane de Cássia , Macedo Ana Paula , Salgado Helio Cesar , Fazan Rubens , Watanabe Evandro , Lovato da Silva Cláudia Helena , Ribeiro Adriana Barbosa
Published: May 2024

BACKGROUND

Tooth loss has been established as a correlate with an increased risk of cardiovascular disease (CVD) and hypertension. However, the influence of complete denture usage on hypertension remains inadequately explored in scientific literature.

METHODS

This case-control study evaluated the microbial load of the biofilm of dentures and the palate, salivary levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17) and Salivary Flow (SF) of healthy (CG), controlled hypertensives (G1), underreported hypertensives (G2) and uncontrolled hypertensives (G3). The sample was characterized by sociodemographic data, clinical information, systolic (SBP), and Diastolic Blood Pressure (DBP). The microbial load ofCandidaspp.,Staphylococcusspp., enterobacteria, and mutans group streptococci was evaluated by quantifying colony-forming unit (CFU), SF of unstimulated saliva by mL per minute, and salivary cytokines by flow cytometry.

RESULTS

80 patients were evaluated (66±7.2 years). The time of edentulism was longer in G3 and positively associated with SBP. The CFU of mutans group streptococci on the denture was higher in G3 and showed a negative association with smoking habit, and this had a positive association with salivary cytokines (IL-4, IL-2, IL-17, IFN-γ), diabetes, and CVD. Patients in group G3, who only use upper dentures, had significantly higher SBP (p=0.024) and levels of IL-2 (p=0.024).

CONCLUSIONS

Time of edentulism may play a role in hypertension. Smoking habits modulated microbiota and interleukins, especially in diabetic and CVD patients. Furthermore, non-functional dentures had an association with hypertensive patients not controlled by medication, reflected in an increase in SBP and IL-2.
Association between enterotypes of the gut microbiota and features of stroke
Authors: Ogata Toshiyasu , Arima Hisatomi , Kawazoe Miki , Baba Yasuhiko
Published: May 2024

Background

An enterotype (e.g., generaBacteroidesandPrevotella) is a classification of patients’ gut microbes into three types, and these types differ in their features of cardiovascular disease. We hypothesized that patients have different enterotypes depending on their arteriosclerosis risk factors, stroke subtype, and severity of stroke.

Methods

Stool specimens were collected from 100 patients (age: 73.4 ± 11.3 years, 62 men, 38 women) with ischemic stroke after consent was obtained. Data on age, sex, risk of arteriosclerosis, stroke subtype, history of stroke, neurological severity at admission, and prognosis were obtained from the patients’ medical records. Phylogenetic analyses of the 16S rRNA gene (V3–V4 region) extracted from each stool sample were performed. Quantitative analyses of the presence of each bacterial genus in the intestines were performed using a next-generation sequencer. After the number of each genus of gut microbes was extracted, ≥ 30% of the patients with the genusBacteroideswere classified as type I, ≥ 15% with the genusPrevotellawere classified as type II, and the rest were classified as type III. We analyzed the association between the patients’ enterotypes and their characteristics (i.e., arteriosclerosis risk factors such as stroke subtype, and severity of stroke).

Results

Thirty-three patients had type I, 10 had type II, and 57 had type III, with no overlap. Patients with types I and II had a lower prevalence of dyslipidemia than those with type III (types I vs II vs III: 36% vs 20% vs 58%, P = 0.028), a lower National Institute of Health and Stroke Scale score at admission (1 vs 1 vs 4 [median], P = 0.025), and the modified Rankin Scale score at discharge tended to be lower (1 vs 1 vs 2 [median], P = 0.094).

Conclusions

The enterotype may affect the risk factors and severity of ischemic stroke.
Intermittent theta burst stimulation (iTBS)-induced changes of resting-state brain entropy (BEN)
Authors: Liu Pan-Shi , Song Dong-Hui , Deng Xin-Ping , Shang Yuan-Qi , Ge Qiu , Wang Ze , Zhang Hui
Published: May 2024

Intermittent theta burst stimulation (iTBS) is a novel protocol of repetitive transcranial magnetic stimulation (rTMS). While iTBS has shown better therapeutic effects for depression than conventional high-frequency rTMS (HF-rTMS), its underlying neuronal mechanism remains elusive. Brain entropy (BEN), a measure of irregularity of brain activity, has recently emerged as a novel marker of regional brain activity. Our previous studies have shown the sensitivity of BEN to depression and HF-rTMS, suggesting BEN as a sensitive tool for understanding the brain mechanism of iTBS. To assess this possibility, we calculated BEN using resting state fMRI data provided by an open dataset in OpenNeuro. Sixteen healthy participants underwent 600 pulses of iTBS applied over the left dorsolateral prefrontal cortex (L-DLPFC) at two intensities (90% and 120% of individual resting motor threshold (rMT)) on separate days. We assessed the pre-post stimulation BEN difference and its associations with neurotransmitter receptor and transporter binding maps. Our results showed that subthreshold iTBS (90% rMT) decreased striatal BEN, while suprathreshold iTBS (120% rMT) increased striatal BEN. We also found significant differences in the spatial correlation between BEN changes induced by different stimulation intensities and various neurotransmitters. These results suggest that differences in BEN caused by iTBS stimulation intensity may be related to the release of other neurotransmitters. The study underscores the significance of iTBS stimulation intensity and provides a basis for future clinical investigations to identify stimulation intensities with good therapeutic benefits.
Tissue growth associated transition of podoplanin-expressing stromal cells in the postnatal mouse femur
Authors: Notoh Hinako , Nara Rikuto , Suzuki Nobuaki , Suzuki Atsuo , Okamoto Shuichi , Tsukiji Nagaharu , Kanematsu Takeshi , Suzuki Naruko , Katsumi Akira , Kojima Tetsuhito , Suzuki-Inoue Katsue , Matsushita Tadashi , Tamura Shogo
Published: May 2024

Skeletal stem/progenitor cells are tissue-resident stem/progenitor cells involved in the formation of the skeletal tissue, bone marrow, and hematopoietic microenvironment. Podoplanin-expressing stromal cells (PDPN-SCs) are skeletal stem/progenitor cell-lineage stromal cells. In the adult mouse bone marrow, PDPN-SCs are present on the diaphyseal arterioles and promote megakaryo/erythropoiesis. However, the localized distribution of PDPN-SCs in neonatal and postnatal femurs remains unclear. In this study, we histologically examined the transition of PDPN-SCs during postnatal femoral growth. In the diaphyseal marrow, PDPN-SCs were present in the neonatal marrow space but disappeared with femoral growth. In the cortical bone, abundant PDPN-SCs existed in the primitive neonatal bone and transitioned to restricted localization in the periosteum and endosteum with tissue growth. In the metaphysis, PDPN-SCs resided in nascent trabecular bones. We also found a novel subset of PDPN-SCs that expressed osterix, suggesting that osterix-positive PDPN-SCs were involved in bone formation. Furthermore, in the diaphyseal arterioles, periarteriolar PDPN-SCs appeared sporadically between 1–2 weeks of age and populated to surround the arterioles. These histological observations can contribute to the understanding of how stromal cells, including PDPN-SCs, engage in postnatal bone and marrow formation.
WOLO: Wilson Only Looks Once – Estimating ant body mass from reference-free images using deep convolutional neural networks
Authors: Plum Fabian , Plum Lena , Bischoff Corvin , Labonte David
Published: May 2024

Size estimation is a hard computer vision problem with widespread applications in quality control in manufacturing and processing plants, livestock management, and research on animal behaviour. Image-based size estimation is typically facilitated by either well-controlled imaging conditions, the provision of global cues, or both. Reference-free size estimation remains challenging, because objects of vastly different sizes can appear identical if they are of similar shape. Here, we explore the feasibility of implementing automated and reference-free body size estimation to facilitate large-scale experimental work in a key model species in sociobiology: the leaf-cutter ants. Leaf-cutter ants are a suitable testbed for reference-free size estimation, because their workers differ vastly in both size and shape; in principle, it is therefore possible to infer body mass - a proxy for size - from relative body proportions alone. Inspired by earlier work by E.O. Wilson, who trained himself to discern ant worker size from visual cues alone, we deployed deep learning techniques to achieve the same feat automatically, quickly, at scale, and from reference-free images: Wilson Only Looks Once (WOLO). Using 150,000 hand-annotated and 100,000 computer-generated images, a set of deep convolutional neural networks were trained to estimate the body mass of ant workers from image cutouts. The best-performing WOLO networks achieved errors as low as 11% on unseen data, approximately matching or exceeding human performance, measured for a small group of both experts and non-experts, but were about 1000 times faster. Further refinement may thus enable accurate, high throughput, and non-intrusive body mass estimation in behavioural work, and so eventually contribute to a more nuanced and comprehensive understanding of the rules that underpin the complex division of labour that characterises polymorphic insect societies.
Mechanics of knee meniscus results from precise balance between material microstructure and synovial fluid viscosity
Authors: Afanador Camilo A.S. , Urcun Stéphane , Sbalzarini Ivo F. , Bordas Stéphane P.A. , Barrera Olga , Rajabi Mohammad Mahdi , Seil Romain , Obeidat Anas
Published: May 2024

The meniscus plays a crucial role in the biomechanics of the knee, serving as load transmitter, and reducing friction between joints. Understanding the biome-chanics of the meniscus is essential to effective treatments of knee injuries and degenerative conditions. In this study, we used two central meniscus samples extracted from a human knee and acquired high-resolutionµ-CT images. Using an implicit immersed boundary technique, we reconstructed two 3D computational models of the menisci. By eroding the channels of the original meniscus geometry, we created new microstructures with varying porosities (0.53to0.8) whilst preserving the connectivity of the porous structure. We investigate the fluid dynamics of the meniscus using a mesh-free numerical method, considering various inlet pressure conditions and analysing the fluid flow within the microstructures. The results of the original microstructure associated with a physiological dynamic viscosity of synovial fluid are in accordance with biophysical experiments on menisci. Furthermore, the eroded microstructure with a33%increase in porosity exhibited a remarkable120%increase in flow velocity. This emphasises the sensitivity of meniscus physiology to porous microstructure properties, showing that detailed computational models can explore physiological and pathological conditions, advancing further knee biomechanics research.
Efficient DNA base editing via an optimized DYW-like deaminase
Authors: Kweon Jiyeon , Park Soomin , Jeon Mi Yeon , Lim Kayeong , Jang Gayoung , Jang An-Hee , Lee Minyoung , Seok Cheong , Lee Chaeyeon , Park Subin , Ahn Jiseong , Jang JiYoon , Sung Young Hoon , Kim Daesik , Kim Yongsub
Published: May 2024

CRISPR-based cytosine base editors enable precise genome editing without inducing double-stranded DNA breaks, yet traditionally depend on a limited selection of deaminases from the APOBEC/AID or TadA families. Here, we introduce SsCBE, a novel CRISPR-based cytosine base editor utilizing SsdAtox, a DYW-like deaminase derived from the toxin ofPseudomonas syringae. Strategic engineering of SsdAtoxhas led to remarkable improvements in the base editing efficiency (by up to 8.4-fold) and specificity for SsCBE, while concurrently reducing cytotoxicity. Exhibiting exceptional versatility, SsCBE was delivered and efficiently applied using diverse delivery methods, including the engineered virus-like particles (eVLPs). Its application has enabled targeted cytosine base editing in mouse zygotes and pioneering edits in mitochondrial DNA. The advent of SsCBE marks a significant advancement in the CRISPR toolkit, providing a versatile tool for advanced research and therapeutic strategies.
Methodology for isolation of serum, cerebrospinal fluid, and hippocampal neuron proteins from rat and their analysis using mass spectrometry-based shotgun proteomics
Authors: Sharma Pratibha , Dhamija Rajinder K
Published: May 2024

Emerging interests in the field of research related to diseases such as Alzheimer’s disease, Parkinson’s disease, cognition, and other mental health-related disorders have prompted a need for a common method for the isolation of serum, CSF, and hippocampus. The hippocampus is responsible for learning and memory. It can be affected by various neurological and psychiatric disorders. However, the process of collecting samples such as CSF and hippocampal neurons is challenging, especially for small animals like rats. We have presented here a method for the isolation of serum, CSF, and hippocampal neurons that can be used for its downstream applications such as proteomics. We have used high-speed centrifugation instruments and density gradient centrifugation methods, which are easy to follow. Additionally, we have tested the proteins identified through mass spectrometry. Our method enables the study of proteins in serum, CSF, and neural cells for researching protein cross-talks and neurological disorder mechanisms.
Epidemiology of Myalgic Encephalomyelitis among individuals with self-reported Chronic Fatigue Syndrome in British Columbia, Canada, and their health-related quality of life
Authors: Chuluunbaatar-Lussier Enkhzaya , Tsai Melody , Boulter Travis , Muñoz Carola , Kerr Kathleen , Nacul Luis
Published: May 2024

Background

There is no accurate data on the epidemiology of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) in Canada. The aims of the study were to describe the epidemiology of confirmed ME/CFS cases and their health-related quality of life (HRQoL).

Methods

This is a cross-sectional study with British Columbia Generations Project (BCGP) participants who self-reported having CFS and population-based controls with no fatiguing illness. Participants completed the Symptoms Assessment Questionnaire, RAND 36-item Health Survey, and Phenotyping Questionnaire Short-form. These assessments enabled the identification and characterization of “confirmed cases” of ME/CFS. Those with self-reported diagnoses who did not meet study diagnosis of ME/CFS were subcategorized as “non-ME/CFS cases.”

Results

We included 187 participants, 45.5% (n=85) self-reported cases and 54.5% (n=102) controls; 34% (n=29) of those who self-reported ME/CFS fulfilled diagnostic criteria for ME/CFS. The population prevalence rates were 1.1% and 0.4% for self-reported and confirmed ME/CFS cases respectively. Participants displayed significantly lower scores in all eight SF-36 domains compared to the other groups. Mental component scores were similar between ME/CFS and non-ME/CFS groups. The main risk factor for low HRQoL scores was fatigue severity (β = - 0.6, p<0.001 for physical health; β = -0.7, p<0.001 for mental health).

Conclusions

The majority of self-reported cases do not meet diagnostic criteria for ME/CFS, suggesting that self-reported CFS may not be a reliable indicator for a true ME/CFS diagnosis. HRQoL indicators were consistently lower in ME/CFS and non-ME/CFS cases compared to controls, with ME/CFS cases having lower scores in most domains. Having higher symptom severity scores and perceived poorer health were the significant affecting factors of lower

HRQoL. Although self-report can be used as screening to identify cases in populations, we suggest studies of ME/CFS should include appropriate medically confirmed clinical diagnosis for validity. Further large-scale population-based studies with simultaneous medical assessment are suggested to further characterize validity parameters of self-reported diagnosis.
A rapid review of the effectiveness of interventions to enhance equitable or overall access to mental health services by ethnic minority groups
Authors: Edwards Deborah , Csontos Judit , Gillen Elizabeth , Gwyn Sioned , Hounsome Juliet , Kiseleva Meg , Mann Mala , Sha'aban Abubakar , Lewis Ruth , Edwards Rhiannon Tudor K , Davies Jacob , Cooper Alison , Edwards Adrian G
Published: May 2024

Abstract: It is estimated that one in four people will experience poor mental health throughout their lifetime. However, ethnic minority groups, refugees and asylum seekers experience more barriers accessing mental health services and have poorer mental health outcomes than those from non-ethnic minority groups. Evidence suggests that interventions that improve access and engagement with mental health services may help reduce disparities affecting ethnic minority groups. This review aims to assess the effectiveness of interventions that enhance equitable or overall access to mental health services by ethnic minority groups. The review included evidence available up until 19th December 2023. Psycho-educational interventions that focused on providing culturally appropriate information, showed mixed results for help seeking behaviour, improvements in depressions stigma. Multi-component interventions within healthcare settings had mixed results. Some studies showed positive outcomes; such as increased help seeking intentions and improved attendance rates, while others did not show significant differences in outcomes. Interventions that included integrating specialist mental health services within primary care resulted in variable outcomes. The findings of interventions incorporating language support into mental health services were also variable. The effectiveness of interventions to enhance the cultural competency of mental health services varied across studies. Research Implications and Evidence Gaps: Future research should prioritise rigorous study designs, including randomised controlled trials and longitudinal studies. More research is required to compare outcomes between ethnic minority participants and White participants. Economic considerations: Ethnic minority individuals are disproportionately affected by economic determinants of poor mental health including increased likelihood of low income. Future research should investigate the economic benefit from an NHS and societal perspective of improving access to mental health services for ethnic minority individuals.
Neurodevelopmental and psychiatric conditions in 600 Swedish Children with the ARFID phenotype
Authors: Nyholmer Manda , Wronski Marie-Louis , Hog Liv , Kuja-Halkola Ralf , Lichtenstein Paul , Lundström Sebastian , Larsson Henrik , Taylor Mark J. , Bulik Cynthia M. , Dinkler Lisa
Published: May 2024

Objective

Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder characterized by extremely restricted dietary variety and/or quantity resulting in serious consequences for physical health and psychosocial functioning. ARFID often co-occurs with neurodevelopmental conditions (NDCs) and psychiatric conditions, but previous data are mostly limited to small clinical samples examining a narrow range of conditions. Here, we examined NDCs and psychiatric conditions in a large, population-based group of children with ARFID.

Method

In a sample of 30,795 children born 1992–2008 in Sweden, ARFID was assessed using parent reports and clinical diagnoses from national health registers. Parents further reported symptoms of NDCs and psychiatric conditions at child age 9 or 12 years. We conducted regressions for symptom scores and screening diagnoses (identified using validated cut offs) on ARFID and examined interactions with sex.

Results

Children with ARFID had significantly increased odds of all 17 screening diagnoses with odds ratios ranging from 3.3 for visual hallucinations to 13.7 for autism (all p<.0001). The most common NDCs were oppositional defiant disorder (19.4%), ADHD (16.9%), tic disorders (14.8%), and autism (12.1%). Among psychiatric conditions, separation anxiety disorder (29.0%) and sleep problems (20.0%) had the highest prevalence. We did not find any sex-specific differences in co-occurring conditions.

Conclusion

This study highlights the co-occurrence of a broad range of NDCs and psychiatric conditions with ARFID in a large, non-clinical cohort. Our findings underscore that children with ARFID face significant burden from multiple co-existing conditions which should be considered during assessment and treatment.
Contralateral Neck Recurrence Rates After Ipsilateral Neck Adjuvant Radiation in Head and Neck Carcinomas with a Pathologically Negative Contralateral Neck
Authors: Kiser Kendall J. , Apicelli Anthony J. , Brenneman Randall J. , Contreras Jessika A. , Gay Hiram , Moravan Michael J. , Rammohan Nikhil , Jackson Ryan S. , Pipkorn Patrik , Puram Sidharth V. , Rich Jason T. , Zevallos Jose P. , Adkins Douglas R. , Oppelt Peter , Thorstad Wade L.
Published: May 2024

Introduction

In 2019 we published a phase II trial of ipsilateral neck adjuvant radiation therapy in head and neck (HN) carcinoma patients with a pathologically negative (pN0) contralateral neck after bilateral neck dissection. The five-year contralateral neck recurrence rate was 3%. Here we present the recurrence rate in patients subsequently treated by this trial’s paradigm.

Methods

Patients were selected who would have been eligible for our phase II trial: all had oropharynx, hypopharynx, oral cavity, or unknown primary carcinomas without prior HN cancer or major HN surgeries, underwent primary resection including bilateral neck dissection with a pN0 contralateral neck, and underwent adjuvant intensity modulated radiation therapy (IMRT) that spared the contralateral neck.

Results

Fifty-five patients met cohort inclusion criteria. Thirty-nine cancers arose from the oropharynx, 11 from the oral cavity, three from the hypopharynx, and two from an unknown primary. With a median follow-up of 15 months there were nine recurrences (16%), four contralateral neck recurrences (7%), and one isolated contralateral neck recurrence (2%). No contralateral neck recurrences occurred in patients with p16+ oropharyngeal primaries despite that most (73%) arose from the base of the tongue. In contrast, three contralateral neck recurrences occurred in patients with advanced stage oral cavity primaries.

Conclusion

The contralateral neck recurrence rate in HN carcinoma patients with a pN0 contralateral neck treated by adjuvant ipsilateral neck IMRT was similar to the 3% rate observed in our phase II trial. However, this paradigm may be inadequate for patients with locally advanced oral cavity primaries.
Mapping vascular network architecture in primate brain using ferumoxytol-weighted laminar MRI
Authors: Autio Joonas A. , Kimura Ikko , Ose Takayuki , Matsumoto Yuki , Ohno Masahiro , Urushibata Yuta , Ikeda Takuro , Glasser Matthew F. , Van Essen David C. , Hayashi Takuya
Published: May 2024

Mapping the vascular organization of the brain is of great importance across various domains of basic neuroimaging research, diagnostic radiology, and neurology. However, the intricate task of precisely mapping vasculature across brain regions and cortical layers presents formidable challenges, resulting in a limited understanding of neurometabolic factors influencing the brain’s microvasculature. Addressing this gap, our study investigates whole-brain vascular volume using ferumoxytol-weighted laminar-resolution multi-echo gradient-echo imaging in macaque monkeys. We validate the results with published data for vascular densities and compare them with cytoarchitecture, neuron and synaptic densities. The ferumoxytol-induced change in transverse relaxation rate (ΔR2*), an indirect proxy measure of cerebral blood volume (CBV), was mapped onto twelve equivolumetric laminar cortical surfaces. Our findings reveal that CBV varies 3-fold across the brain, with the highest vascular volume observed in the inferior colliculus and lowest in the corpus callosum. In the cerebral cortex, CBV is notably high in early primary sensory areas and low in association areas responsible for higher cognitive functions. Classification of CBV into distinct groups unveils extensive replication of translaminar vascular network motifs, suggesting distinct computational energy supply requirements in areas with varying cytoarchitecture types. Regionally, baseline R2* and CBV exhibit positive correlations with neuron density and negative correlations with receptor densities. Adjusting image resolution based on the critical sampling frequency of penetrating cortical vessels allows us to delineate approximately 30% of the arterial-venous vessels. Collectively, these results mark significant methodological and conceptual advancements, contributing to the refinement of cerebrovascular MRI. Furthermore, our study establishes a linkage between neurometabolic factors and the vascular network architecture in the primate brain.

Highlights

Cortical layer vascular mapping using ferumoxytol-weighted R2* MRI

Vascular volume is high in primary sensory areas and low in association areas

Correlation between R2* and vascular volume with neuron and receptor densities

Vascularization co-varies with densities of specific interneuron types
A foundation model for generalizable cancer diagnosis and survival prediction from histopathological images
Authors: Yang Zhaochang , Wei Ting , Liang Ying , Yuan Xin , Gao Ruitian , Xia Yujia , Zhou Jie , Zhang Yue , Yu Zhangsheng
Published: May 2024

Computational pathology, utilizing whole slide image (WSI) for pathological diagnosis, has advanced the development of intelligent healthcare. However, the scarcity of annotated data and histological differences hinder the general application of existing methods. Extensive histopathological data and the robustness of self-supervised models in small-scale data demonstrate promising prospects for developing foundation pathology models. Due to the need for deployment, lightweight foundation models also need to be developed. In this work, we propose the BEPH (BEiT-based modelPre-training onHistopathological images), a general lightweight foundation model that leverages self-supervised learning to learn meaningful representations from 11 million unlabeled histopathological images. These representations are then efficiently adapted to various tasks, including 2 cancer patch-level recognition tasks, 3 cancer WSI-level classification tasks, and 6 cancer subtypes survival prediction tasks. Experimental results demonstrate that our model consistently outperforms several comparative models with similar parameters, even with limited training data reduced to 50%. Especially when the downstream structure is the same, the model can improve ResNet and DINO by up to a maximum increase of 8.8% and 7.2% (WSI level classification), and 6.44% and 3.28% on average (survival prediction), respectively. Therefore, BEPH offers a universal solution to enhance model performance, reduce the burden of expert annotations, and enable widespread clinical applications of artificial intelligence. The code and models can be obtained athttps://github.com/Zhcyoung/BEPH. And currently, online fine-tuning of WSI classification tasks is available for use onhttp://yulab-sjtu.natapp1.cc/BEPH.
A Demographic-Conditioned Variational Autoencoder for fMRI Distribution Sampling and Removal of Confounds
Authors: Orlichenko Anton , Qu Gang , Zhou Ziyu , Liu Anqi , Deng Hong-Wen , Ding Zhengming , Stephen Julia M. , Wilson Tony W. , Calhoun Vince D. , Wang Yu-Ping
Published: May 2024

Objective

fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging.

Methods

We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevel-opmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP).

Results

We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity.

Conclusion

Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics.

Significance

Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds.
A Novel Explainable AI Method to Assess Associations between Temporal Patterns in Patient Trajectories and Adverse Outcome Risks: Analyzing Fitness as a Risk Factor of ADRD
Authors: Shao Yijun , Zamrini Edward Y. , Ahmed Ali , Cheng Yan , Nelson Stuart J. , Kokkinos Peter , Zeng-Treitler Qing
Published: May 2024

We present a novel explainable artificial intelligence (XAI) method to assess the associations between the temporal patterns in the patient trajectories recorded in longitudinal clinical data and the adverse outcome risks, through explanations for a type of deep neural network model called Hybrid Value-Aware Transformer (HVAT) model. The HVAT models can learn jointly from longitudinal and non-longitudinal clinical data, and in particular can leverage the time-varying numerical values associated with the clinical codes or concepts within the longitudinal data for outcome prediction. The key component of the XAI method is the definitions of two derived variables, the temporal mean and the temporal slope, which are defined for the clinical concepts with associated time-varying numerical values. The two variables represent the overall level and the rate of change over time, respectively, in the trajectory formed by the values associated with the clinical concept. Two operations on the original values are designed for changing the values of the two derived variables separately. The effects of the two variables on the outcome risks learned by the HVAT model are calculated in terms of impact scores and impacts. Interpretations of the impact scores and impacts as being similar to those of odds ratios are also provided. We applied the XAI method to the study of cardiorespiratory fitness (CRF) as a risk factor of Alzheimer’s disease and related dementias (ADRD). Using a retrospective case-control study design, we found that each one-unit increase in the overall CRF level is associated with a 5% reduction in ADRD risk, while each one-unit increase in the changing rate of CRF over time is associated with a 1% reduction. A closer investigation revealed that the association between the changing rate of CRF level and the ADRD risk is nonlinear, or more specifically, approximately piecewise linear along the axis of the changing rate on two pieces: the piece of negative changing rates and the piece of positive changing rates.
In vivosequential mutagenesis in germinal center B cells using a dual-recombinase approach: FOXO1 re-expression upon FOXO1 knockout rescues class switch recombination
Authors: Díaz Carlota Farré , Kabrani Eleni , Winkler Wiebke , Salomon Claudia , Wunderlich F. Thomas , Janz Martin , Rajewsky Klaus
Published: May 2024

Modeling complex (patho)physiological processes by sequential mutagenesis in mice is limited by the lack of optimized genetic tools and complex breeding strategies. We present a new Cre/DreERT2 dual-recombinase germinal center B-cell (GCBC)- specific strain, with co-expression of the recombinases from a single allele. This enables highly efficient Cre-mediated FOXO1 knockout followed by time-controlled, efficient Dre-mediated FOXO1 re-expression and functional rescue in GCBCs, demonstrating suitability for precise targeted sequential mutagenesisin vivo.
Glial cell activation precedes neurodegeneration in the cerebellar cortex of the YG8-800 murine model of Friedreich’s ataxia
Authors: Vicente-Acosta Andrés , Herranz-Martín Saúl , Pazos María Ruth , Galán-Cruz Jorge , Amores Mario , Loria Frida , Díaz-Nido Javier
Published: May 2024

Friedreich’s ataxia is a hereditary neurodegenerative disorder resulting from reduced levels of the protein frataxin due to an expanded GAA repeat in theFXNgene. This deficiency causes progressive degeneration of specific neuronal populations in the cerebellum and the consequent loss of movement coordination and equilibrium, some of the main symptoms observed in affected individuals. Similar to other neurodegenerative diseases, previous studies suggest that glial cells could be involved in the neurodegenerative process and disease progression in Friedreich’s ataxia.

In this work, we have followed and characterized the progression of changes in the cerebellar cortex of the latest Friedreich’s ataxia humanized mouse model, the YG8-800 (Fxnnull:YG8s(GAA)>800), which carries a humanFXNtransgene containing more than 800 GAA repeats.

Comparative analyses of behavioral, histopathological, and biochemical parameters were conducted between Y47R control and YG8-800 mice at different time points. Our findings revealed that the YG8-800 mice display an ataxic phenotype, characterized by poor motor coordination, lower body weight, cerebellar atrophy, neuronal loss, and changes in synaptic proteins. Additionally, early activation of glial cells, predominantly astrocytes and microglia, was observed preceding neuronal degeneration along with an increased expression of key pro-inflammatory cytokines and downregulation of neurotrophic factors.

Together, our results show how the YG8-800 mouse model exhibits a stronger phenotype than previous experimental murine models, reliably recapitulating some of the features observed in the human condition. Accordingly, this humanized model could represent a valuable tool to study Friedreich’s ataxia molecular disease mechanisms and for preclinical evaluation of possible therapies.
Developmental olfactory dysfunction and abnormal odor memory in immune-challengedDisc1+/-mice
Authors: Parbst Fiona , Kostka Johanna K. , Günther Anne , Chen Yu-Nan , Hanganu-Opatz Ileana L. , Bitzenhofer Sebastian H.
Published: May 2024

Neuronal activity in the olfactory bulb (OB) drives coordinated activity in the hippocampal-prefrontal network during early development. Inhibiting OB output in neonatal mice disrupts functional development of the hippocampal formation as well as cognitive abilities. These impairments manifest early in life and resemble dysfunctions of the hippocampus and the prefrontal cortex that have been linked to neuropsychiatric disorders. Thus, we investigated a disease mouse model and asked whether activity in the OB might be altered, thereby contributing to the dysfunctional development of the hippocampal-prefrontal network. We addressed this question by combining in vivo electrophysiology with behavioral assessment of immune-challengedDisc1+/-mice that mimic the dual genetic-environmental etiology of neuropsychiatric disorders. In wildtype mice, we found high DISC1 expression levels in OB projection neurons during development. Furthermore, neuronal and network activity in the OB, as well as the drive from the bulb to the hippocampal-prefrontal network were reduced in immune-challengedDisc1+/-mice during early development. This early deficit did not affect odor-evoked activity and odor perception but resulted in impaired long-term odor memory. We propose that reduced endogenous activity in the developing OB contributes to altered maturation of the hippocampal-prefrontal network, leading to memory impairment in immune-challengedDisc1+/-mice.
Associated production of heavy quarkonia and
D
mesons in the improved color evaporation model with KaTie
Authors: Chernyshev A. A. , Saleev V. A.
Published: May 2024

In this article, we study associated production of prompt J/ψ(ϒ) and D mesons in the improved color evaporation model using the high-energy factorization approach as it is realized in the Monte Carlo event generator KaTie. The modified Kimber-Martin-Ryskin-Watt model for unintegrated parton distribution functions is used. We predict cross sections for associated J/ψ(ϒ) and D meson hadroproduction via the single and double parton scattering mechanisms using the set of model parameters which has been fixed early for description of prompt single and pair heavy quarkonium production at the LHC energies. We found the results of calculations agree with the LHCb Collaboration data at the energies s=7, 8 TeV and we present theoretical predictions for the energy s=13  TeV.

Published by the American Physical Society
2024
Robust constraints on feebly interacting particles using XMM-Newton
Authors: Luque Pedro De la Torre , Balaji Shyam , Carenza Pierluca
Published: May 2024

During galactic supernova (SN) explosions, a large amount of feebly interacting particles (FIPs) may be produced. In this work we analyze electrophilic FIPs with masses in the MeV-range that escape from SN and decay into electron-positron pairs, causing an exotic leptonic injection. This contribution adds up to known components, leading to an unexpected excess of x-ray fluxes generated by inverse-Compton scattering of the injected particles on low-energy photon backgrounds. For the first time in the context of FIPs, we use XMM-Newton x-ray measurements to obtain the strongest and most robust bounds on electrophilic FIPs produced by SN in our Galaxy.

Published by the American Physical Society
2024
Temperature Impact on Lithium Metal Morphology in Lithium Reservoir-Free Solid-State Batteries
Authors: Jeong Min-Gi , Hatzell Kelsey B. , Banerjee Sourim , Vishnugopi Bairav S. , Mukherjee Partha P.
Published: May 2024

Lithium reservoir-free solid-state batteries can offer exceedingly high energy densities for a range of emerging applications related to aviation and electric vehicles. However, reversible operation of reservoir-free cells is plagued by a range of degradation mechanisms. The morphology of lithium metal film and subsequent evolution during operation can be highly variable and is dependent on the type of solid electrolyte, current collector, and operating conditions (current density, temperature, pressure, etc.). Here we evaluate lithium metal vertical and horizontal growth mechanisms at an argyrodite solid electrolyte–stainless steel interface at various temperatures from 25 to 80∘C. Combining confocal imaging and mesoscale modeling, we demonstrate how lithium metal island agglomeration is accelerated at elevated temperatures and facilitates greater horizontal growth of lithium metal. Maintaining high active material contact (e.g., horizontal growth) is critical for the formation of reversible lithium metal anodes in reservoir-free cells.

Published by the American Physical Society
2024
Mapping the foundations and evolution of career aspiration research: a bibliometric analysis
Authors: Wang Yiming , Liu Doudou , Li Chaoping
Published: May 2024

Purpose

This bibliometric literature review aims to uncover the (1) intellectual foundations and (2) topical evolution in the field of career aspiration research.

Design/methodology/approach

We employed the systematic literature review methodology following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. According to the predetermined criteria, 286 articles were included from the Web of Science database. Then, we employed performance analysis, science mapping and natural language processing to address our research objectives.

Findings

Co-citation analysis uncovered four foundational themes: (1) gender and leadership aspiration, (2) Social Cognitive Career Theory, (3) process of career development and (4) adolescents’ career aspiration. Moreover, co-word analysis showed that scholarly foci have shifted from adolescents’ career development to diverse streams. This shift was indicated by the exploration of additional research samples, such as university students, and topics related to specific aspirations (e.g. entrepreneurial and managerial aspirations) and gender issues (e.g. women leadership and gender stereotypes).

Research limitations/implications

Although this review has limitations related to data selection, it presents implications for practice, theory and future research on career aspirations.

Originality/value

The study illuminated the past and development of a research domain, thus advancing the understanding of career aspirations and inspiring future research.