bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the pain experience of lionfish envenomation
Authors: Mouchbahani-Constance Stephanie , Choinière Manon , Sharif-Naeini Reza 
Published: August 2023

Abstract

Introduction:
Stings from the lionfish (Pterois volitans) constitute one of the most painful wounds in the ocean. This species has invaded the Atlantic coast of the United States, Gulf of Mexico, Caribbean, and Mediterranean Sea. In addition to its ecological impact on local fish populations, stings from the lionfish pose a medical problem because of the debilitating nature of the pain they produce. However, there are no studies examining the human pain experience of lionfish stings.

Objective:
To characterize the various aspects of the pain experience following a lionfish sting.

Methods:
We developed a pain questionnaire that includes validated scales used with patients having acute or chronic pain to understand the pain variability, as well as the use of health care resources and treatments.

Results:
We provide the first study of the pain experience from lionfish stings. Here, we show that the pain is intense from the start and peaks approximately 1 hour later, resolving itself in 7 days for most victims. Furthermore, pain intensity can be influenced by several factors, including (1) age of the victim, where older victims experience significantly higher pain intensities, (2) the number of spines involved, (3) and whether infection occurred at the injury site. However, pain intensity was not different between male and female participants.

Conclusion:
These findings will inform the medical community on the pain experience and can be used by local authorities to better appreciate the impact of lionfish envenomations to develop programs aimed at curtailing the expansion of the lionfish.
Tactile acuity improves during acute experimental pain of the limb
Authors: Paredes Sanchez Judith , Titmus Morgan , Lawson-Smith Hollie , Di Pietro Flavia 
Published: August 2023

Abstract

Introduction:
Chronic pain is associated with poor tactile acuity, commonly measured with the 2-point discrimination (TPD) test. Although poor tactile acuity across chronic pain conditions is well established, less is known in acute pain.

Objective:
Recent conflicting findings in experimentally induced neck and back pain led us to conduct a TPD investigation in experimentally induced limb pain. We hypothesised altered TPD during experimental upper limb pain, but we did not speculate on the direction of the change.

Methods:
Thirty healthy subjects immersed their dominant hand in a circulating cold-water bath at 7°C (cold pressor test [CPT]). Two-point discrimination was measured at baseline (pre-CPT), during pain (during-CPT), and after withdrawal from the water (post-CPT) in 3 different sites: (1) the dominant forearm, (2) dominant arm and (3) contralateral forearm.

Results:
Repeated-measures analysis of variance revealed a significant main effect of time (F(2,56) = 4.45, P = 0.02,

= 0.14) on TPD; in all 3 sites, TPD values decreased (ie, tactile acuity improved) during pain. Interestingly, the contralateral forearm followed a similar pattern to the dominant (ie, painful) forearm, and furthermore was the only site that exhibited any correlation with pain, albeit in an intriguing direction (r = 0.57, P = 0.001), ie, the greater the pain the worse the tactile acuity.

Conclusion:
The improvements in tactile acuity during experimentally induced limb pain may reflect a protective response. The changes in the corresponding site in the contralateral limb may reflect a protective spinal cross talk. Such a response, together with the interesting relationship between tactile acuity and pain, warrant further inquiry.
Intimate Partner Violence and Inflammaging: Conflict Tactics Predict Inflammation Among Middle-Aged and Older Adults
Authors: Madison Annelise A. , Wilson Stephanie J. , Shrout M. Rosie , Malarkey William B. , Kiecolt-Glaser Janice K. 
Published: August 2023

Abstract

Objective
In long-term relationships, conflict is inevitable, but physical and psychological aggression is not. Intimate partner violence (IPV) is a known risk factor for age-related disease onset, and inflammation likely links the two. This study explores relationships between frequency of constructive (i.e., negotiation) and destructive (i.e., aggression) conflict tactics with inflammation in both younger and older adulthood. Based on the theory of inflammaging, the study investigates whether these associations were stronger in mid-to-late adulthood.

Methods
At one visit, 214 participants in long-term romantic relationships had their blood drawn to assess six inflammatory markers (interleukin-6, IL-6; tumor necrosis factor-alpha, TNF-α; c-reactive protein, CRP; serum amyloid A, SAA; soluble intercellular adhesion molecule, sICAM; soluble vascular cell adhesion molecule, sVCAM) and reported frequency of destructive and constructive conflict tactics with their partner in the past year on the Revised Conflict Tactics Scale short form.

Results
Age interacted with number of destructive conflicts per year to predict serum IL-6 (F(1, 200) = 5.3, p = .022), TNF-α (F(1, 180) = 4.2, p = .043), sICAM (F(1, 193) = 7.0, p = .008), and marginally SAA (F(1, 199) = 3.7, p = .055), such that middle-aged and older adults who reported more destructive tactics had higher inflammation. Also, the relationship between constructive conflict frequency and TNF-α also depended on age (F(1, 177) = 4.9, p = .029), in that older adults who reported a greater number of constructive tactics had lower TNF-α.

Conclusion
Couples’ conflict tactics may influence levels of inflammation, and, therefore, aging rate, in mid-to-late life. Middle-aged and older adults may disproportionately benefit from a healthy partnership and suffer from an unhealthy partnership.
CIRCTDRD9 CONTRIBUTES TO SEPSIS-INDUCED ACUTE LUNG INJURY BY ENHANCING THE EXPRESSION OF RAB10 VIA DIRECTLY BINDING TO MIR-223-3P
Authors: Zhang Rui , Dang Xiaoyan , Liu Jie , Feng Hui , Sun Jiangli , Peng Zhuo 
Published: August 2023

ABSTRACT

Background: The dysregulation of circular RNAs (circRNAs) is involved in various human diseases, including sepsis-induced acute lung injury (ALI). We aimed to investigate the role of circTDRD9 in the development of sepsis-induced ALI. Methods: Cell models of sepsis-induced ALI were established by treating A549 cells with LPS. The expression of circTDRD9, miR-223-3p, and RAB10 mRNA was measured by quantitative real-time PCR (qPCR). The levels of inflammatory factors were measured by ELISA. Oxidative stress-related indicators were monitored by using commercial detection kits. The expression of fibrosis-related proteins was detected by Western blot assay. Cell proliferation was assessed by EdU assay. The predicted binding relationship between miR-223-3p and circTDRD9 or RAB10 was verified by dual-luciferase reporter assay, RIP assay or pull-down assay. Results: CircTDRD9 was highly expressed in LPS-treated A549 cells. CircTDRD9 downregulation prevented LPS-induced inflammation, oxidative stress, cell proliferation inhibition, and cell fibrosis in A549 cells, whereas these effects were reversed by the inhibition of miR-223-3p, a target of circTDRD9. In addition, RAB10 was verified as a target of miR-223-3p, and RAB10 overexpression recovered LPS-induced inflammation, oxidative stress, cell proliferation inhibition, and cell fibrosis in A549 cells that were ameliorated by miR-223-3p restoration. Importantly, circTDRD9 positively regulated RAB10 expression by binding to miR-223-3p. Conclusion: CircTDRD9 overexpression was closely associated with LPS-induced ALI. CircTDRD9 contributed to LPS-induced ALI partly by upregulating RAB10 via binding to miR-223-3p.
SULFORAPHANE ALLEVIATES POSTRESUSCITATION LUNG PYROPTOSIS POSSIBLY VIA ACTIVATING THE NRF2/HO-1 PATHWAY
Authors: Li Yulin , Yang Minfei , Xie Lutao , Zhang Gongping , Xu Jiefeng , Xu Shanxiang 
Published: August 2023

ABSTRACT

Introduction: Sulforaphane (SFN), known as the activator of the nuclear factor E2–related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, has been proven to protect the lung against various pathological stimuli. The present study aimed to investigate the effect of SFN on lung injury induced by systemic ischemia reperfusion after cardiac arrest and resuscitation. Methods: After animal preparation, 24 pigs were randomly divided into sham group (n = 6), cardiopulmonary resuscitation group (CPR, n = 9), or CPR + SFN group (n = 9). The experimental model was then established by 10 min of cardiac arrest followed by 6 min of CPR. Once spontaneous circulation was achieved, a dose of 2 mg/kg of SFN diluted in 20 mL of saline was intravenously infused with a duration of 5 min. During 4 h of observation after resuscitation, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index were regularly evaluated. At 24 h after resuscitation, lung tissues were harvested to evaluate the score of lung histopathological injury, the activity of superoxide dismutase, the contents of malondialdehyde, IL-1β, and IL-18, and the expression levels of NOD-like receptor pyrin domain 3, cleaved caspase 1, gasdermin D (GSDMD), GSDMD N-terminal, Nrf2, and HO-1. Results: During CPR, spontaneous circulation was achieved in six and seven pigs in the CPR and CPR + SFN groups, respectively. After resuscitation, the indicators of lung injury (ELWI, PVPI, and oxygenation index) were all better in the CPR + SFN group than in the CPR group, in which the differences in ELWI and PVPI at 2, and 4 h after resuscitation were significant between the two groups. In addition, SFN significantly reduced lung injury score, improved oxidative imbalance (superoxide dismutase, malondialdehyde), decreased pyroptosis-related proinflammatory cytokines (IL-1β, IL-18), downregulated pyroptosis–related proteins (NOD-like receptor pyrin domain 3, cleaved caspase 1, GSDMD, GSDMD N-terminal), and activated the Nrf2/HO-1 pathway when compared with the CPR group. Conclusion: SFN produced effective postresuscitation lung protection through alleviating lung pyroptosis possibly via activating the Nrf2/HO-1 pathway in pigs.
Large language models approach expert-level clinical knowledge and reasoning in ophthalmology: A head-to-head cross-sectional study
Authors: Thirunavukarasu Arun James , Mahmood Shathar , Malem Andrew , Foster William Paul , Sanghera Rohan , Hassan Refaat , Zhou Sean , Wong Shiao Wei , Wong Yee Ling , Chong Yu Jeat , Shakeel Abdullah , Chang Yin-Hsi , Tan Benjamin Kye Jyn , Jain Nikhil , Tan Ting Fang , Rauz Saaeha , Ting Daniel Shu Wei , Ting Darren Shu Jeng 
Published: August 2023

ABSTRACTObjectiveTo evaluate the clinical potential of large language models (LLMs) in ophthalmology using a more robust benchmark than raw examination scores.Materials and methodsGPT-3.5 and GPT-4 were trialled on 347 questions before GPT-3.5, GPT-4, PaLM 2, LLaMA, expert ophthalmologists, and doctors in training were trialled on a mock examination of 87 questions. Performance was analysed with respect to question subject and type (first order recall and higher order reasoning). Masked ophthalmologists graded the accuracy, relevance, and overall preference of GPT-3.5 and GPT-4 responses to the same questions.ResultsThe performance of GPT-4 (69%) was superior to GPT-3.5 (48%), LLaMA (32%), and PaLM 2 (56%). GPT-4 compared favourably with expert ophthalmologists (median 76%, range 64-90%), ophthalmology trainees (median 59%, range 57-63%), and unspecialised junior doctors (median 43%, range 41-44%). Low agreement between LLMs and doctors reflected idiosyncratic differences in knowledge and reasoning with overall consistency across subjects and types (p>0.05). All ophthalmologists preferred GPT-4 responses over GPT-3.5 and rated the accuracy and relevance of GPT-4 as higher (p<0.05).DiscussionIn view of the comparable or superior performance to trainee-grade ophthalmologists and unspecialised junior doctors, state-of-the-art LLMs such as GPT-4 may provide useful medical advice and assistance where access to expert ophthalmologists is limited. Clinical benchmarks provide useful assays of LLM capabilities in healthcare before clinical trials can be designed and conducted.ConclusionLLMs are approaching expert-level knowledge and reasoning skills in ophthalmology. Further research is required to develop and validate clinical applications to improve eye health outcomes.
Forced-rate aerobic cycling enhances motor recovery in persons with chronic stroke: A randomized clinical trial
Authors: Linder Susan M. , Bischof-Bockbrader Andrea , Davidson Sara , Li Yadi , Lapin Brittany , Singh Tamanna , Lee John , Bethoux Francois , Alberts Jay L. 
Published: August 2023

ABSTRACTBackground:The potential for intensive aerobic exercise to enhance neuroplasticity post-stroke has been theorized but not systematically investigated. Our aim was to determine the effects of forced-rate aerobic exercise paired with an abbreviated session of upper extremity (UE) repetitive task practice (FE+RTP) compared to time-matched UE repetitive task practice (RTP only) on the recovery of motor function in individuals with chronic stroke.Methods:A single center randomized clinical trial was conducted from April 2019 to December 2022. Sixty individuals ≥6 months following single stroke with residual UE hemiparesis aged 18-85 were recruited. Participants were randomized 1:1 to one of two time-matched groups: FE+RTP (N=30) or RTP only (N=30). Both groups completed 90-minute sessions, 3x/week for 8 weeks. The FE+RTP group underwent 45-minutes of forced-rate aerobic exercise (FE) followed by 45-min of UE RTP. The RTP only group completed 2 sequential 45-minute sessions of UE RTP. The primary UE outcomes were the Fugl-Meyer Assessment (FMA) and the Action Research Arm Test (ARAT). The Six-minute Walk Test (6MWT) assessed walking capacity.Results:Sixty individuals 60.5 (±10.6) years of age and 26.0 [13.0, 69.0] months post-stroke were enrolled, and 56 completed the study. The RTP only group completed more RTP in terms of repetitions (411.8±44.4 versus 222.8±28.4, P<0.001) and time (72.7±6.7 versus 37.8±2.4 minutes, P<0.001) compared to FE+RTP. Both groups improved on the FMA (FE+RTP, 36.2±10.1 to 44.0±11.8 and RTP only, 34.4±11.0 to 41.2±13.4, P<0.001) and ARAT (FE+RTP, 32.5±16.6 to 37.7±17.9 and RTP only, 32.8±18.6 to 36.4±18.5, P<0.001). A group main effect was not observed. The FE+RTP group demonstrated greater improvements on the 6MWT (274.9±122.0 to 327.1±141.2 meters) compared to the RTP only group (285.5±160.3 to 316.9±170.0, P=0.004).ConclusionsWhile both interventions elicited comparable improvements in UE motor recovery, the summative value of FE+RTP in improving UE and lower extremity function was demonstrated.Trial Registration:ClinicalTrials.gov:NCT03819764
Subgrouping patients with comorbidity between functional dyspepsia and irritable bowel syndrome: application of multidimensional item response theory and latent profile analysis
Authors: Zhongyu Huang , Zipan Lyu , Fengbin Liu 
Published: August 2023

AbstractBackgroundComorbidity between different subtypes of functional gastrointestinal disorders(FGIDs) is of high prevalence in clinical practice. Heterogeneity of clinical appearances has led to difficulty in individualized diagnosis and comprehensive management of FGIDs.AimsTo discover the hidden clinical patterns of patients with comorbidity between functional dyspepsia(FD) and irritable bowel syndrome(IBS).MethodsIn a retrospective cross-section study, a self-report questionnaire that consist of items indicating 5 different assessing domains including gastrointestinal discomforts, systemic discomforts, psychological disorders, and environmental aggravated factors was used as basic instrument for clinical assessment. With item response theory, the theoretical framework of assessment was evaluated, and latent traits of patient were quantified in the simulated computerized adaptive testing. Latent class analysis was used for uncovering the hidden patterns over the heterogenous clinical appearances. And differences among the profiles were compared referring to the spectrum of clinical appearances and the clinical diagnosis.ResultsWith 996 patients enrolled in the study, the validity and reliability of the instrument were evaluated as adequate (Cronbach’s alpha indices =0.72, Split-half reliability =0.84). The construct validity was also evaluated to be adequate with Chi-square/df=3.45, CFI=0.92, GFI=0.96, RMSEA=0.05, TLI=0.90, RMR=0.02. The 7-profile model was evaluated to be with better fitness with Entropy=0.98, Lo-Mendell-Rubin likelihood ratio test-pvalue<0.01, Bootstrap likelihood ratio test-pvalue<0.01. And the patterns detailed the heterogeneity of clinical appearance of FGIDs patients either in general condition or discomfort in specific dimension.ConclusionsWith application of multidimensional variable analysis, this article summarized the hidden patterns beneath the heterogenous clinical features. And quantitative approaches helped equip clinician with individualized and comprehensive tool in the management of complex diseases such as FGIDs.
Factors affecting social integration after road traffic orthopaedic injuries in Rwanda
Authors: Ingabire JC Allen , Stewart Aimee , Uwakunda Carine , Mugisha Didace , Sagahutu JB , Urimubenshi Gerard , Tumusiime David K. , Bucyibaruta Georges 
Published: August 2023

AbstractBackgroundRoad traffic injuries (RTIs) leading to long-term disability present a significant public health challenge, causing immense personal and societal consequences. However, in many developing countries, information on the social integration of patients post-RTI remains limited.PurposeThis study aimed to identify factors contributing to social integration following road traffic-related orthopedic injuries in Rwanda.MethodologyThe research encompassed a multicenter, cross-sectional study involving 369 adult RTI victims from five Rwandan referral hospitals, all of whom experienced accidents in 2019. Participants completed the IMPACT-S Questionnaire, which evaluated the level of social integration in terms of activities and participation. Statistical analysis using logistic regression, with a significance level set at p<0.05, helped estimate odds ratios (OR) and 95% confidence intervals (CI). We obtained ethical approval to conduct the study from the University of Rwanda, College of Medicine and Health Sciences Institutional Review Board. All participants signed a written consent before enrollment into the study, and all data were kept confidential and only used for the purpose of this study.ResultsThe study’s findings indicated that the mean age of RTI victims was 37.5±11.26 years, with a notable male predominance over females. Of the participants, 5.69% were unable to resume normal life activities. The overall mean score on the IMPACT-S scale was moderate, at 77±17. Specifically, participants achieved an average score of 76±16 for “activities” and a higher average of 84±16 for “participation.” Certain factors were associated with poor social integration compared to others, including belonging to the age group above 65 years (OR=8.25, p=0.02), female sex (OR=3.26, p=0.02), lack of rehabilitation (OR=3.82, p=0.01), and length of hospital stay > 15 days (OR=4.44, p=0.02).ConclusionThe majority of RTI victims in Rwanda achieved successful reintegration into society; nevertheless, their mobility and community engagement were more significantly impacted compared to other aspects assessed by the IMPACT-S scale. The study emphasized the importance of early management, effective rehabilitation, and prompt patient discharge from the hospital in facilitating a successful return to everyday life after road traffic-related orthopedic injuries.
Cell wall integrity modulates a PHYTOCHROME-INTERACTING FACTOR (PIF) – HOOKLESS1 (HLS1) signalling module controlling apical hook formation in Arabidopsis
Authors: Lorrai Riccardo , Erguvan Özer , Raggi Sara , Jonsson Kristoffer , Široká Jitka , Tarkowská Danuše , Novák Ondřej , Verger Stéphane , Robert Stéphanie , Ferrari Simone 
Published: August 2023

SummaryEtiolated seedlings of dicots form an apical hook to protect the meristems during soil emergence. Hook formation is the result of differential growth on both sides of the hypocotyl apex and is tightly controlled by environmental cues and hormones, among which auxin and gibberellins (GAs) are the main contributors. Cell expansion is tightly regulated by the cell wall, but whether and how feedback from this structure contributes to hook development is still unclear. Here we show that etiolated seedlings of theArabidopsis thaliana quasimodo2-1(qua2) mutant, defective in pectin biosynthesis, display severe defects in apical hook formation and maintenance, accompanied by loss of asymmetric auxin maxima and differential cell expansion. Moreover,qua2seedlings show reduced expression ofHOOKLESS1(HLS1) andPHYTOCHROME-INTERACTING FACTOR 4and5(PIF4/5), positive regulators of hook formation, and accumulate reduced levels of the active gibberellin GA4. Treatment of wild-type seedlings with the cellulose inhibitor isoxaben (isx) also prevents hook development and repressesHLS1expression and PIF4 accumulation. Moreover, isx stabilizes the DELLA protein REPRESSOR OFga1-3(RGA), which inhibitsHLS1expression and hook formation. Exogenous GAs orHLS1overexpression partially restore hook development in isx-treated seedlings. Notably, agar concentration in the medium restores, both inqua2and isx-treated seedlings, hook development and WT-like levels of PIFs and HLS1. We propose that turgor-dependent signals link changes in cell wall integrity to the PIF4/5-HLS1 signalling module to repress differential cell elongation during hook formation.Significance statementCell wall integrity modulates apical hook development through poorly understood mechanisms. We show here that, in Arabidopsis, repression of hook formation by either mutations in pectin biosynthesis or by isoxaben treatment is at least partially mediated by the downregulation of a gibberellin-controlled signalling module that comprises PIF4/5 and HLS1. Our results indicate that the signals derived from changes in the cell wall can modulate hormone-mediated pathways to control asymmetric growth during plant development.
Inhibition ofCERS1in skeletal muscle exacerbates age-related muscle dysfunction
Authors: Wohlwend Martin , Laurila Pirkka-Pekka , Goeminne Ludger J.E. , Lima Tanes , Daskalaki Ioanna , Li Xiaoxu , von Alvensleben Giacomo , Crisol Barbara , Mangione Renata , Gallart-Ayala Hector , Burri Olivier , Butler Stephen , Morris Jonathan , Turner Nigel , Ivanisevic Julijana , Auwerx Johan 
Published: August 2023

ABSTRACTAge-related muscle wasting and dysfunction render the elderly population vulnerable and incapacitated, while underlying mechanisms are poorly understood. Here, we implicate theCERS1enzyme of the de novo sphingolipid synthesis pathway in the pathogenesis of age-related skeletal muscle impairment. In humans,CERS1abundance declines with aging in skeletal muscle cells and, correlates with biological pathways involved in muscle function and myogenesis. Furthermore,CERS1is upregulated during myogenic differentiation. Pharmacological or genetic inhibition ofCERS1in aged mice blunts myogenesis and deteriorates aged skeletal muscle mass and function, which is associated with the occurrence of morphological features typical of inflammation and fibrosis. Ablation of theCERS1orthologuelagr-1inC. eleganssimilarly exacerbates the age-associated decline in muscle function and integrity. We discover genetic variants reducingCERS1expression in human skeletal muscle and Mendelian randomization analysis in the UK biobank cohort shows that these variants reduce muscle grip strength and overall health. In summary, our findings link age-related impairments in muscle function to a reduction inCERS1, thereby underlining the importance of the sphingolipid biosynthesis pathway in age-related muscle homeostasis.