bluuebunny/crossref_metadata_2025_split huggingface dataset:
Having More Tender Than Swollen Joints Is Associated With Worse Patient-Reported Outcomes in Patients With Early RA
Authors: Meng Charis F. , Lee Yvonne C. , Schieir Orit , Valois Marie-France , Butler Margaret A. , Boire Gilles , Hazlewood Glen , Hitchon Carol , Keystone Edward , Tin Diane , Thorne Carter , Bessette Louis , Pope Janet , Bartlett Susan J. , Bykerk Vivian P. ,   on behalf of the Canadian Early Arthritis Cohort Investigators
Published: May 2024

Background/Objective
In patients with rheumatoid arthritis (RA), high tender-swollen joint differences (TSJDs) have been associated with worse outcomes. A better understanding of the phenotype and impact of high TSJD on patient-reported outcomes (PROs) in early RA may lead to earlier personalized treatment targeting domains that are important to patients today. Our objectives were to evaluate the impact of TSJD on updated PROs in patients with early RA over 1 year and to determine differences in associations by joint size.

Methods
This longitudinal cohort study followed patients with active, early RA enrolled in the Canadian Early Arthritis Cohort between 2016 and 2022, who completed clinical assessments and PROMIS-29 measures over 1 year. Twenty-eight joint counts were performed and TSJDs calculated. Adjusted associations between TSJD and PROMIS-29 scores were estimated using separate linear-mixed models. Separate analyses of large versus small-joint TJSDs were performed.

Results
Patients with early RA (n = 547; 70% female; mean [SD] age, 56 [15] years; mean [SD] symptom duration, 5.3 [2.9] months) were evaluated. A 1-point increase in TSJD was significantly associated with worse PROMIS T-scores in all domains: physical function (adjusted regression coefficient, −0.27; 95% confidence interval [CI], −0.39, −0.15), social participation (adjusted regression coefficient, −0.34; 95% CI, −0.50, −0.19), pain interference (adjusted regression coefficient, 0.49; 95% CI, 0.35, 0.64), sleep problems (adjusted regression coefficient, 0.29; 95% CI, 0.16, 0.43), fatigue (adjusted regression coefficient, 0.34; 95% CI, 0.18, 0.50), anxiety (adjusted regression coefficient, 0.23; 95% CI, 0.08, 0.38), and depression (adjusted regression coefficient, 0.20; 95% CI, 0.06, 0.35). Large-joint TSJD was associated with markedly worse PROs compared with small-joint TSJD.

Conclusions
Elevated TSJD is associated with worse PROs particularly pain interference, social participation, and fatigue. Patients with more tender than swollen joints, especially large joints, may benefit from earlier, targeted therapeutic interventions.
Bilateral Adrenal Metastasis of Prostatic Adenocarcinoma on 68Ga-PSMA PET/CT Imaging
Authors: Beyhan Ediz , Turan Bektaş Ceyda , Baloğlu Mehmet Can , Tosunoğlu Zehranur , Çermik Tevfik Fikret 
Published: May 2024

Abstract
An 84-year-old man with prostate adenocarcinoma underwent 68Ga-PSMA PET/CT due to PSA recurrence. Foci of 68Ga-PSMA uptake were observed in bilateral adrenal glands. Adrenal MRI showed metastasis only in the left adrenal gland. Metastatic 68Ga-PSMA uptake was also observed in the mediastinum and bone. Enzalutamide treatment was started. Follow-up 68Ga-PSMA PET/CT scan showed regression in both adrenal gland metastases and other metastases.
Two Cases of Synchronous Hodgkin Lymphoma and Papillary Thyroid Carcinoma in 18F-FDG PET/CT
Authors: Wang Ru , Cai Haidong , Liu Changcun , LV Zhongwei , Ma Chao 
Published: May 2024

AbstractThe concurrence of Hodgkin lymphoma and papillary thyroid carcinoma is a rare clinical event. Two women presented with a painless mass in the neck that was suspected malignancy by ultrasonography. Both cases shown in the18F-FDG PET/CT images demonstrated multiple foci of increased FDG uptake in the neck, mimicking thyroid carcinoma with contralateral cervical lymph node metastases. Unexpectedly, the postoperative pathologies confirmed the thyroid lesion of papillary carcinoma and contralateral cervical lymph nodes of classical Hodgkin lymphoma.
Transcriptome Sequencing of the Oral Mucosa Reveals Gene Expression Differences in Patients With Parry-Romberg Syndrome
Authors: Ma Lun-kun , Zhang Zhi-yong , Tang Xiao-jun , Liu Wei , Xu Xi , Feng Shi , Zhao Shan-baga , Liu Bing-yang , Zang Tian-ying , Li Chuan 
Published: May 2024

Objective:Parry-Romberg syndrome (PRS) is an acquired disease characterized by progressive unilateral atrophy of the facial skin, subcutaneous tissue, muscle, and bone. There are various hypotheses to try to explain the occurrence of the disease, but the specific etiology and pathogenesis remain unclear. This study aimed to explore the potential molecular pathogenesis of the disease by using next-generation RNA-sequencing technology.Methods:The authors collected oral mucosal tissue from the affected side and the healthy side from 3 patients with PRS. Tissue samples were subjected to RNA extraction, whole transcriptome sequencing, and bioinformatics analysis. Differentially expressed genes were obtained from both groups of samples and then analyzed for functional enrichment.Results:A total of 186 differentially expressed genes were screened from the 2 groups of samples. Compared with the healthy side, several immune-related genes, including immunoglobulin kappa variable (IGKV)2D-28, IGKV1D-33, IGKV1-33, and NLRP10, were significantly upregulated in the affected tissue. In addition, the differential genes were significantly enriched in metabolic pathways including pancreatic secretion, protein and fat digestion, and absorption.Conclusions:The authors described the gene expression differences between the affected and healthy tissues of patients with PRS for the first time. Immune responses may play a role in the pathogenesis of PRS.
Renal protective effect and clinical analysis of vitamin B6 in patients with sepsis
Authors: Wang Yao , Lu Wen-Long , Feng Wen-Ming , Xu Wei , Liu Li-hua , He Li-Min 
Published: May 2024

AbstractObjectiveTo investigate the protective effect and possible mechanisms of vitamin B6 against renal injury in patients with sepsis.MethodsA total of 128 patients with sepsis who met the entry criteria in multiple centres were randomly divided into experimental (intravenous vitamin B6 therapy) and control (intravenous 0.9% sodium chloride therapy) groups based on usual care. Clinical data, the inflammatory response indicators interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrosis factor (TNF-α) and endothelin-1 (ET-1), the oxidative stress response indicators superoxide dismutase, glutathione and malondialdehyde, and renal function (assessed by blood urea nitrogen [BUN], serum creatinine [SCr] and renal resistance index [RRI] monitored by ultrasound) were compared between the two groups.ResultsAfter 7 d of treatment, the IL-6, IL-8, TNF-α and ET-1 levels in the experimental group were significantly lower than those in the control group, the oxidative stress response indicators were significantly improved in the experimental group and the BUN, SCr and RRI values in the experimental group were significantly lower than those in the control group (p< 0.05). There was no statistical difference between the two groups in the rate of renal replacement therapy and 28 d mortality (p> 0.05). However, the ICU length of stay and the total hospitalisation expenses in the experimental group were significantly lower than those in the control group (p< 0.05).ConclusionThe administration of vitamin B6 in the treatment of patients with sepsis attenuates renal injury, and the mechanism may be related to pyridoxine decreasing the levels of inflammatory mediators and their regulation by redox stress.Clinical trial registration: ClinicalTrials.gov Identifier: NCT06008223
Gun violence revictimization in New York State: What increases the risk of being shot again?
Authors: L’Huillier Joseph C. , Boccardo Joseph D. , Stewart Morgan , Wang Suiyuan , Myneni Ajay A. , Bari ASM Abdul , Nitsche Lindsay J. , Taylor Henry L. , Lukan James , Noyes Katia 
Published: May 2024

BACKGROUNDWhile gun injuries are more likely to occur in urban settings and affect people of color, factors associated with gun violence revictimization—suffering multiple incidents of gun violence—are unknown. We examined victim demographics and environmental factors associated with gun violence revictimization in New York State (NYS).METHODSThe 2005 to 2020 NYS hospital discharge database was queried for patients aged 12 years to 65 years with firearm-related hospital encounters. Patient and environmental variables were extracted. Patient home zip code was used to determine the Social Deprivation Index (SDI) for each patient’s area of residence. We conducted bivariate and multivariate analyses among patients who suffered a single incident of gun violence or gun violence revictimization.RESULTSWe identified 38,974 gun violence victims among whom 2,243 (5.8%) suffered revictimization. The proportion of revictimization rose from 4% in 2008 to 8% in 2020 (p< 0.01). The median [interquartile range] time from first to second incident among those who suffered revictimization was 359 days [81–1,167 days]. Revictimization was more common among Blacks (75.0% vs. 65.1%,p< 0.01), patients with Medicaid (54.9% vs. 43.2%,p< 0.01), and in areas of higher deprivation (84.8 percentile vs. 82.1 percentile,p< 0.01).CONCLUSIONGun violence revictimization is on the rise. People of color and those residing in areas with high social deprivation are more likely to be re-injured. Our findings emphasize the importance of community-level over individual-level interventions for prevention of gun violence revictimization.LEVEL OF EVIDENCEPrognostic and Epidemiological; Level IV.
Horizontal running inside circular walls of Moon settlements: a comprehensive countermeasure for low-gravity deconditioning?
Authors: Minetti Alberto E. , Luciano Francesco , Natalucci Valentina , Pavei Gaspare 
Published: May 2024

Long-lasting exposure to low gravity, such as in lunar settlements planned by the ongoing Artemis Program, elicits muscle hypotrophy, bone demineralization, cardio-respiratory and neuro-control deconditioning, against which optimal countermeasures are still to be designed. Rather than training selected muscle groups only, ‘whole-body’ activities such as locomotion seem better candidates, but at Moon gravity both ‘pendular’ walking and bouncing gaits like running exhibit abnormal dynamics at faster speeds. We theoretically and experimentally show that much greater self-generated artificial gravities can be experienced on the Moon by running horizontally inside a static 4.7 m radius cylinder (motorcyclists’ ‘Wall of Death’ of amusement parks) at speeds preventing downward skidding. To emulate lunar gravity, 83% of body weight was unloaded by pre-tensed (36 m) bungee jumping bands. Participants unprecedentedly maintained horizontal fast running (5.4–6.5 m s
−1
) for a few circular laps, with intense metabolism (estimated as 54–74 mlO
2
kg
−1
min
−1
) and peak forces during foot contact, inferred by motion analysis, of 2–3 Earth body weight (corresponding to terrestrial running at 3–4 m s
−1
), high enough to prevent bone calcium resorption. A training regime of a few laps a day promises to be a viable countermeasure for astronauts to quickly combat whole-body deconditioning, for further missions and home return.
Sacrificing Adaptability for Functionality: The Ivory Tower of Macular Müller Cells
Authors: Zhang Ting , Jin Kaiyu , Zeng Shaoxue , Yang Penghui , Zhu Meidong , Zhang Jialing , Chen Yingying , Lee Sora , Yam Michelle , Zeng Yue , Lu Xiaoyan , Loo Lipin , Neely G. Gregory , Chang Andrew , Zhou Fanfan , Du Jianhai , Fan Xiaohui , Zhu Ling , Gillies Mark C. 
Published: May 2024

AbstractThe predilection of many retinal diseases for the macula suggests it may be less resistant to stress than the peripheral retina. Profiling of single-cell level transcriptional changes found that the peripheral retina exhibited more transcriptional changes than the macula in response to stress. One pronounced change was in a subgroup of Müller cells (MCs) that were dominant in the peripheral retina. Genes more abundantly expressed in peripheral MCs were mainly associated with stress responses and were more influenced by light stress. In contrast, genes highly expressed in MCs that predominated in the macula had roles in cellular function and were less influenced by light stress. Metallothionein 1, A Kinase Anchor Protein 12 and MAF BZIP Transcription Factor F were more abundantly expressed in peripheral MCs than in macular MCs. Knockdown of these genes in primary MCs reduced their viability under stress. Our findings indicate that macular MCs are more directed toward maintaining retinal function rather than mounting a stress response when exposed to stress, which may contribute to the macula’s vulnerability to degenerative diseases.
Impacts of the feedback loop between sense-antisense RNAs in regulating circadian rhythms
Authors: Uriu Koichiro , Hernandez-Sanchez Juan P. , Kojima Shihoko 
Published: May 2024

AbstractAntisense transcripts are a unique group of non-coding RNAs that are transcribed from the opposite strand of a sense coding gene in an antisense orientation. Even though they do not encode a protein, these transcripts play a regulatory role in a variety of biological processes, including circadian rhythms. We and others found an antisense transcript,Per2AS, that is transcribed from the strand opposite the sense transcriptPeriod2(Per2) and exhibits a rhythmic and antiphasic expression pattern compared toPer2in mouse. By assuming thatPer2ASandPer2mutually repress each other, our previous mathematical model predicted thatPer2ASregulates the robustness and the amplitude of circadian rhythms. In this study, we revised our previous model and developed a new mathematical model that mechanistically described the mutually repressive relationship betweenPer2andPer2ASvia transcriptional interference. We found that the simulation results are largely consistent with experimental observations including the counterintuitive ones that could not be fully explained by our previous model. These results indicate that our revised model serves as a foundation to build more detailed models in the future to better understand the impact ofPer2AS-Per2interaction in the mammalian circadian clock. Our mechanistic description ofPer2AS-Per2interaction can also be extended to other mathematical models that involve sense-antisense RNA pairs that mutually repress each other.
Roodmus: A toolkit for benchmarking heterogeneous electron cryo-microscopy reconstructions
Authors: Joosten Maarten , Greer Joel , Parkhurst James , Burnley Tom , Jakobi Arjen J. 
Published: May 2024

AbstractConformational heterogeneity of biological macromolecules is a challenge in single particle averaging (SPA). Current standard practice is to employ classification and filtering methods which may allow a discrete number of conformational states to be reconstructed. However, the conformation space accessible to these molecules is continuous and therefore explored incompletely by a small number of discrete classes. Recently developed heterogeneous reconstruction algorithms (HRAs) to analyse continuous heterogeneity rely on machine learning methods employing low-dimensional latent space representations. The non-linear nature of many of these methods pose challenges to their validation and interpretation, and to identifying functionally relevant conformational trajectories. We believe these methods would benefit from in-depth benchmarking using high quality synthetic data and concomitant ground truth information. Here we present a framework for the simulation and subsequent analysis with respect to ground-truth of cryo-EM micrographs containing particles whose conformational heterogeneity is sourced from molecular dynamics simulations. This synthetic data can then be processed as if it were experimental data allowing aspects of standard SPA workflows, as well as heterogeneous reconstruction methods, to be compared with known ground-truth using available utilities. We will demonstrate the simulation and analysis of several such datasets and present an initial investigation into HRAs.
Investigating intestinal epithelium metabolic dysfunction in Celiac Disease using personalized genome-scale models
Authors: McCreery Chloe V. , Alessi Drew , Mollo Katarina , Fasano Alessio , Zomorrodi Ali R. 
Published: May 2024

AbstractCeliac Disease (CeD) is an autoimmune condition characterized by an aberrant immune response triggered by the ingestion of gluten, which damages epithelial cells lining the small intestine. Small intestinal epithelial cells (sIECs) play a key role in various metabolic processes, including the enzymatic digestion and absorption of nutrients. Although nutritional malabsorption is widely recognized in CeD, the underlying disrupted metabolic processes remain largely undefined. To address this knowledge gap, we constructed personalized gender-specific genome-scale models of sIEC metabolism using transcriptional data from 42 subjects with active CeD, remission CeD, and healthy controls. We computationally simulated these models under a relevant diet for each group of subjects to assess the activity of 59 metabolic tasks essential for sIEC function and to profile metabolite secretion into the bloodstream and intestinal lumen. These investigations revealed significant variations in the activity of 25 metabolic tasks in active and remission CeD models. These tasks impact critical processes integral to sIEC function such as amino acid metabolism, nucleotide synthesis and DNA repair, ATP generation, and oxidative stress regulation. Additionally, we identified 54 metabolites with altered secretion profiles in CeD, encompassing amino acids, vitamins, antioxidants, and fatty acids. Furthermore, we pinpointed 22 FDA-approved drugs that target the genes associated with differentially active metabolic functions whose altered activities adversely affect sIECs in CeD, potentially helping to restore their normal activity. Our study unveils new insights into the metabolic reprogramming of sIECs in CeD, paving the way for therapeutic interventions targeting dysregulated metabolic processes.
Altered DNA methylation pattern contributes to differential epigenetic immune signaling in the upper respiratory airway of COVID-19 patients
Authors: Govender Melissa , Das Jyotirmoy , Hopkins Francis R. , Svanberg Cecilia , Nordgren Johan , Hagbom Marie , Klingström Jonas , Nilsdotter-Augustinsson Åsa , Yong Yean K. , Velu Vijayakumar , Raju Sivadoss , Sjöwall Johanna , Shankar Esaki M. , Nyström Sofia , Larsson Marie 
Published: May 2024

AbstractThe emergence of SARS-CoV-2 has had a profound adverse impact on global health and continues to remain a threat worldwide. The disease spectrum of COVID-19 ranges from asymptomatic to fatal clinical outcomes especially in the elderly population and in individuals with underlying medical conditions. The impact of COVID-19 on host immune responses and immune cells at the protein and DNA levels remains largely ambiguous. In a case-control study, here we explored the impact of COVID-19 on DNA methylation patterns in the upper respiratory airway to determine how SARS-CoV-2 infection altered the immune status of individuals requiring hospitalization for COVID-19. We performed DNA methylation arrays on nasopharyngeal swabs at inclusion/hospitalization as well as 6 weeks post-inclusion. Our study reveals a distinct DNA methylation pattern in COVID-19 patients compared to healthy controls, characterized by 317 779 differentially methylated CpGs. Notably, within the transcription start sites and gene body, COVID-19 patients exhibited a higher number of genes/CpGs with elevated methylation levels. Enrichment analysis of methylated genes at transcription start sites highlighted the impact on genes associated with inflammatory responses and immune functions. Some SARS-CoV-2 -induced CpG methylations were transient, returning to normal levels by 6 weeks post-inclusion. Enriched genes of interest included IL-17A, a pivotal cytokine implicated with inflammation and healing, and NUP93, associated with antiviral innate immunity. Further, six genes in our data set, OAS1, CXCR5, APP, CCL20, CNR2, and C3AR1, were found in enrichment analysis with previous COVID-19 studies. Additionally, RNAse1 and RNAse2 emerged as key regulators, while IL-18 played a role in various biological processes in COVID-19 patients. Overall, our results demonstrates that COVID-19 has a major impact on the upper airway by modifying the methylation pattern of many genes and this could have implications for the conditioning of the airways and how the individual response to future airway infections.
Language Models Outperform Cloze Predictability in a Cognitive Model of Reading
Authors: Rego Adrielli Lopes , Snell Joshua , Meeter Martijn 
Published: May 2024

AbstractAlthough word predictability is commonly considered an important factor in reading, sophisticated accounts of predictability in theories of reading are yet lacking. Computational models of reading traditionally use cloze norming as a proxy of word predictability, but what cloze norms precisely capture remains unclear. This study investigates whether large language models (LLMs) can fill this gap. Contextual predictions are implemented via a novel parallel-graded mechanism, where all predicted words at a given position are pre-activated as a function of contextual certainty, which varies dynamically as text processing unfolds. Through reading simulations with OB1-reader, a cognitive model of word recognition and eye-movement control in reading, we compare the model’s fit to eye-movement data when using predictability values derived from a cloze task against those derived from LLMs (GPT2 and LLaMA). Root Mean Square Error between simulated and human eye movements indicates that LLM predictability provides a better fit than Cloze. This is the first study to use LLMs to augment a cognitive model of reading with higher-order language processing while proposing a mechanism on the interplay between word predictability and eye movements.Author SummaryReading comprehension is a crucial skill that is highly predictive of later success in education. One aspect of efficient reading is our ability to predict what is coming next in the text based on the current context. Although we know predictions take place during reading, the mechanism through which contextual facilitation affects ocolarmotor behaviour in reading is not yet well-understood. Here, we model this mechanism and test different measures of predictability (computational vs. empirical) by simulating eye movements with a cognitive model of reading. Our results suggest that, when implemented with our novel mechanism, a computational measure of predictability provide better fits to eye movements in reading than a traditional empirical measure. With this model, we scrutinize how predictions about upcoming input affects eye movements in reading, and how computational approches to measuring predictability may support theory testing. In the short term, modelling aspects of reading comprehension helps reconnect theory building and experimentation in reading research. In the longer term, more understanding of reading comprehension may help improve reading pedagogies, diagnoses and treatments.