bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering the link between environmental factors and coral immunity: A study of fluorescent protein expression and phenoloxidase activity in Acropora cervicornis
Authors: Toledo-Hernández Carlos , Ruiz-Diaz Claudia Patricia , Ramírez-Lugo Juan Sebastian , Torres-Díaz Marielys , Santiago-Pagán Lisby , Bruno-Chardón Andrea , Díaz-Vázquez Liz M. 
Published: March 2023

Worsening environmental conditions due to climate change have profoundly affected the health of coral reefs worldwide. Thus, understanding how corals respond to fluctuating and/or extreme levels of temperature and solar irradiation will guide future protection and restoration efforts of this valuable ecosystem. Herein, we present a study of the immune responses of the endangered coral Acropora cervicornis to seasonal fluctuations in water temperature (WT), light intensity (LI), and water depth. Immune responses were observed by measuring the concentration of green and cyan fluorescent proteins (GFP and CyFP) and the activity of phenoloxidase (PO), an enzyme involved in the biosynthesis of the photoprotective protein melanin. To study these responses, visually healthy A. cervicornis fragments were placed at 8, and 12 m depth, and GFP, CyPF, and PO activity were measured at three-month intervals over a 12-month period. Seawater temperature and light intensity were also measured at each depth during this period. A general linear mixed model was used to determine the effects of seasonal variations of WT, LI, and water depth on the immune proteins. GFP, CyFP, and PO activity varied significantly across time – all higher in late summer/early fall and lower in late winter/early spring. Likewise, WT and LI significantly affected GFP, CyFP, and PO activity. On the other hand, water depth only had a significant effect on fluorescent protein concentrations but not PO activity. Our study demonstrates that corals can modulate these key immune-related proteins throughout natural seasonal fluctuations. That is, increasing in months of higher thermal and light conditions while decreasing in months with mild thermal and light conditions. The phenotypic plasticity of A. cervicornis in adapting to a changing environment underscores the importance that in future studies time of the year should be a meaningful consideration when evaluating the responses of A. cervicornis to the environment.
Nitric oxide-releasing gel accelerates healing in a diabetic murine splinted excisional wound model
Authors: Sivaraj Dharshan , Noishiki Chikage , Kosaric Nina , Kiwanuka Harriet , Kussie Hudson C. , Henn Dominic , Fischer Katharina S. , Trotsyuk Artem A. , Greco Autumn H. , Kuehlmann Britta A. , Quintero Filiberto , Leeolou Melissa C. , Granoski Maia B. , Hostler Andrew C. , Hahn William W. , Januszyk Michael , Murad Ferid , Chen Kellen , Gurtner Geoffrey C. 
Published: March 2023

IntroductionAccording to the American Diabetes Association (ADA), 9–12 million patients suffer from chronic ulceration each year, costing the healthcare system over USD $25 billion annually. There is a significant unmet need for new and efficacious therapies to accelerate closure of non-healing wounds. Nitric Oxide (NO) levels typically increase rapidly after skin injury in the inflammatory phase and gradually diminish as wound healing progresses. The effect of increased NO concentration on promoting re-epithelization and wound closure has yet to be described in the context of diabetic wound healing.MethodsIn this study, we investigated the effects of local administration of an NO-releasing gel on excisional wound healing in diabetic mice. The excisional wounds of each mouse received either NO-releasing gel or a control phosphate-buffered saline (PBS)-releasing gel treatment twice daily until complete wound closure.ResultsTopical administration of NO-gel significantly accelerated the rate of wound healing as compared with PBS-gel-treated mice during the later stages of healing. The treatment also promoted a more regenerative ECM architecture resulting in shorter, less dense, and more randomly aligned collagen fibers within the healed scars, similar to that of unwounded skin. Wound healing promoting factors fibronectin, TGF-β1, CD31, and VEGF were significantly elevated in NO vs. PBS-gel-treated wounds.DiscussionThe results of this work may have important clinical implications for the management of patients with non-healing wounds.
Tuberculosis remains a major burden in systemic lupus erythematosus patients in Durban, South Africa
Authors: Al-arbi Khaled Mohamed Sefow , Magula Nombulelo P. , Mody Girish M. 
Published: March 2023

Objective:Infections are common in systemic lupus erythematosus (SLE), with tuberculosis (TB) being important in an endemic environment. We studied the prevalence and spectrum of TB in SLE in Durban, South Africa.Methods:A medical records review of SLE patients seen over 13-year period, and the demographic data, clinical manifestations, laboratory findings, treatment and outcome were noted.Results:There were 512 SLE patients and 72 (14.1%) had TB. Thirty (41.7%) had pulmonary TB (PTB) and 42 (58.3%) had extra-pulmonary TB (EPTB). The prevalence of TB among the different ethnic groups was 36/282 (12.8%) for Indian people, 29/184 (15.8%) Black African people, 7/26 (26.9%) admixed African people and none among the 18 White people. Comparison of the 72 SLE-TB patients with 72 SLE controls showed no difference in gender, age at SLE diagnosis and disease duration. The SLE-TB patients had a significant increase in the clinical and laboratory features of disease activity (arthritis, mucocutaneous lesions, renal involvement, vasculitis, low complement, raised ds-DNA antibodies), and cumulative prednisone use over the preceding 3 months.Compared to PTB, the EPTB patients were significantly younger, developed TB earlier after SLE diagnosis, and had higher disease activity. The EPTB patients also had increase in features of disease activity (renal, thrombocytopenia, ds–DNA antibodies), and increase in ever use of intravenous methylprednisolone (IV-MP) and mycophenolate mofetil (MMF). On multivariate analysis, the independent risk factors for EPTB were ever use of MMF (p = 0.003) and IV-MP (p = 0.027). Analysis of the cumulative SLE criteria showed renal involvement was an independent risk factor for EPTB. The outcome was similar in both groups.Conclusion:We show an increased prevalence of TB (14.1%) and EPTB (58.3%) in SLE in an endemic area and confirm that features of disease activity and use of immunosuppressive therapy are the major risk factors. Renal involvement (as a cumulative criterion) is an independent risk factor for EPTB.
Restricted and repetitive behaviors and their developmental and demographic correlates in 4–8-year-old children: A transdiagnostic approach
Authors: Keating Jennifer , Van Goozen Stephanie , Uljarevic Mirko , Hay Dale , Leekam Susan R. 
Published: March 2023

Background: Restricted and repetitive behaviors (RRBs) are a broad class of behaviors characterized by frequent action repetition and intense preference for sameness. Research has predominantly focused on RRBs in diagnosed clinical groups, particularly in autism spectrum disorder and genetic disorders. Using a transdiagnostic approach, the current study examined RRBs in a diverse sample of children in relation to developmental and demographic correlates (age, language, non-verbal ability, child anxiety, sex, and socioeconomic status). Separate analyses examined two RRB subtypes; repetitive sensory and motor behaviors (RSMB) and insistence on sameness (IS).Method: Children (N = 260, age 4–8 years, 174 male, 86 female) in mainstream schools identified by teachers as having behavioral, emotional, and/or cognitive difficulties, were assessed using the Repetitive Behavior Questionnaire-2 (RBQ-2), the British Picture Vocabulary Scale (BPVS), Lucid Ability Scale, the Welsh Index of Multiple Deprivation (WIMD) and the Screen for Child Anxiety Related Emotional Disorders (SCARED). Recruitment excluded diagnosed clinical conditions. The Strengths and Difficulties Questionnaire (SDQ) was used to assess children’s difficulties.Results: RRB scores were of high frequency and the scores for the IS were higher than for RSMB. The severity of anxiety symptoms and male sex were significantly associated with both RRB subtypes, and younger age and SES scores were associated with IS. Elevated RRB total and subtype scores were significantly related to SDQ scores for emotion, conduct, hyperactivity, and peer-relations.Discussion: The study provides the first evidence of RRBs in a diverse sample of young children with emerging difficulties in behavior, cognition, and/or emotion. The results contribute to proposals about psychological development in RRB and indicate that RRBs are best represented on a continuum of severity found across children in the early school years. The results support previous findings of a relation between RRB and anxiety reported in clinical samples and importantly, they indicate that it is time to move beyond the study of categorically defined groups and consider correlates of RRBs that include broad indices of mental health and well-being.
Supplementing transcranial direct current stimulation to local infiltration series for refractory neuropathic craniocephalic pain: A randomized controlled pilot trial
Authors: Wandrey Jan D. , Kastelik Joanna , Fritzsche Thomas , Denke Claudia , Schäfer Michael , Tafelski Sascha 
Published: March 2023

BackgroundSome patients with neuralgia of cranial nerves with otherwise therapy-refractory pain respond to invasive therapy with local anesthetics. Unfortunately, pain regularly relapses despite multimodal pain management. Transcranial direct current stimulation (tDCS) may prolong pain response due to neuro-modulatory effects.MethodsThis controlled clinical pilot trial randomized patients to receive anodal, cathodal or sham-tDCS stimulation prior to local anesthetic infiltration. Pain attenuation, quality-of-life and side effects were assessed and compared with historic controls to estimate effects of tDCS stimulation setting.ResultsAltogether, 17 patients were randomized into three groups with different stimulation protocols. Relative reduction of pain intensity in per protocol treated patients were median 73%, 50% and 69% in anodal, cathodal and sham group, respectively (p = 0.726). Compared with a historic control group, a lower rate of responders with 50% reduction of pain intensity indicates probable placebo effects (OR 3.41 stimulation vs. non-stimulation setting, NNT 3.63). 76.9% (n = 10) of tDCS patients reported mild side-effects. Of all initially included 17 patients, 23.5% (n = 4) withdrew their study participation with highest proportion in the cathodal group (n = 3). A sample size calculation for a confirmatory trial revealed 120 patients using conservative estimations.DiscussionThis pilot trial does not support series of anodal tDCS as neuro-modulatory treatment to enhance pain alleviation of local anesthetic infiltration series. Notably, results may indicate placebo effects of tDCS settings. Feasibility of studies in this population was limited due to relevant drop-out rates. Anodal tDCS warrants further confirmation as neuro-modulatory pain treatment option.
Clinicians' preferences for managing aneurysmal subarachnoid hemorrhage using endothelin receptor antagonists
Authors: Heidenreich Sebastian , Trapali Myrto , Krucien Nicolas , Phillips-Beyer Andrea 
Published: March 2023

BackgroundThe endothelin receptor antagonist (ERA) clazosentan is being investigated for the medical prevention of cerebral vasospasm and associated complications, such as delayed cerebral ischemia (DCI), after aneurysmal subarachnoid hemorrhage (aSAH). This study quantified how clinicians weigh the benefits and risks of ERAs for DCI prevention to better understand their treatment needs and expectations.MethodsAn online choice experiment was conducted to elicit preferences of neurologists, intensivists, and neurosurgeons treating aSAH in the US and UK for the use of ERAs. The design of the choice experiment was informed by a feasibility assessment (N = 100), one-on-one interviews with clinicians (N = 10), a qualitative pilot (N = 13), and a quantitative pilot (N = 50). Selected treatment attributes included in the choice experiment were: one benefit (likelihood of DCI); and three risks (lung complications, hypotension, and anemia). In the choice experiment, clinicians repeatedly chose best and worst treatment options based on a scenario of a patient being treated in the ICU after aneurism repair. A correlated mixed logit model determined the relative attribute importance (RAI) and associated highest density interval (HDI) as well as acceptable benefit-risk trade-offs.ResultsThe final choice experiment was completed by 350 clinicians (116 neurologists, 129 intensivists/intensive care clinicians, and 105 neurosurgeons; mean age, 47.4 years). Reducing the likelihood of DCI (RAI = 56.5% [HDI, 53.6–59.5%]) had the largest impact on clinicians' treatment choices, followed by avoiding the risks of lung complications (RAI = 29.6% [HDI, 27.1–32.3%]), hypotension (RAI = 9.2% [HDI, 7.5–10.8%]), and anemia (RAI = 4.7% [HDI, 3.7–5.8%]). Clinicians expected the likelihood of DCI to decrease by ≥8.1% for a 20% increase in the risk of lung complications, ≥2.4% for a 20% increase in the risk of hypotension, and ≥1.2% for a 20% increase in the risk of anemia.ConclusionsClinicians were willing to accept certain increased risks of adverse events for a reduced risk of DCI after aSAH. The likelihood of DCI occurring after aSAH can therefore be considered a clinically relevant endpoint in aSAH treatment development. Thus, evaluations of ERAs might focus on whether improvements (i.e., reductions) in the likelihood of DCI justify the risks of adverse events.
Continuous dynamics in behavior reveal interactions between perceptual warping in categorization and speech-in-noise perception
Authors: Bidelman Gavin M. , Carter Jared A. 
Published: March 2023

IntroductionSpoken language comprehension requires listeners map continuous features of the speech signal to discrete category labels. Categories are however malleable to surrounding context and stimulus precedence; listeners’ percept can dynamically shift depending on the sequencing of adjacent stimuli resulting in a warping of the heard phonetic category. Here, we investigated whether such perceptual warping—which amplify categorical hearing—might alter speech processing in noise-degraded listening scenarios.MethodsWe measured continuous dynamics in perception and category judgments of an acoustic-phonetic vowel gradient via mouse tracking. Tokens were presented in serial vs. random orders to induce more/less perceptual warping while listeners categorized continua in clean and noise conditions.ResultsListeners’ responses were faster and their mouse trajectories closer to the ultimate behavioral selection (marked visually on the screen) in serial vs. random order, suggesting increased perceptual attraction to category exemplars. Interestingly, order effects emerged earlier and persisted later in the trial time course when categorizing speech in noise.DiscussionThese data describe interactions between perceptual warping in categorization and speech-in-noise perception: warping strengthens the behavioral attraction to relevant speech categories, making listeners more decisive (though not necessarily more accurate) in their decisions of both clean and noise-degraded speech.
Individual differences in beta-band oscillations predict motor-inhibitory control
Authors: Ding Qian , Lin Tuo , Cai Guiyuan , Ou Zitong , Yao Shantong , Zhu Hongxiang , Lan Yue 
Published: March 2023

ObjectiveThe ability of motor-inhibitory control is critical in daily life. The physiological mechanisms underlying motor inhibitory control deficits remain to be elucidated. Beta band oscillations have been suggested to be related to motor performance, but whether they relate to motor-inhibitory control remains unclear. This study is aimed at systematically investigating the relationship between beta band oscillations and motor-inhibitory control to determine whether beta band oscillations were related to the ability of motor-inhibitory control.MethodsWe studied 30 healthy young adults (age: 21.6 ± 1.5 years). Stop-signal reaction time (SSRT) was derived from stop signal task, indicating the ability of motor-inhibitory control. Resting-state electroencephalography (EEG) was recorded for 12 min. Beta band power and functional connectivity (including global efficiency) were calculated. Correlations between beta band oscillations and SSRT were performed.ResultsBeta band EEG power in left and right motor cortex (MC), right somatosensory cortex (SC), and right inferior frontal cortex (IFC) was positively correlated with SSRT (P’s = 0.031, 0.021, 0.045, and 0.015, respectively). Beta band coherence between bilateral MC, SC, and IFC was also positively correlated with SSRT (P’s &lt; 0.05). Beta band global efficiency was positively correlated with SSRT (P = 0.01).ConclusionThis is the first study to investigate the relationship between resting-state cortical beta oscillations and response inhibition. Our findings revealed that individuals with better ability of motor inhibitory control tend to have less cortical beta band power and functional connectivity. This study has clinical significance on the underlying mechanisms of motor inhibitory control deficits.
Acid-sensing ion channel 3 is required for agmatine-induced histamine-independent itch in mice
Authors: Zhou Guo-Kun , Xu Wen-Jing , Lu Yi , Zhou Yan , Feng Chen-Zhang , Zhang Jiang-Tao , Sun Shi-Yu , Wang Ruo-Meng , Liu Tong , Wu Bin 
Published: March 2023

IntroductionItch is a common symptom of many skin and systemic diseases. Identifying novel endogenous itch mediators and the downstream signaling pathways involved will contribute to the development of new strategies for the treatment of chronic itch. In the present study, we adopted behavioral testing, patch clamp recording and metabonomics analysis to investigate the role of agmatine in itch and the underlying mechanism.MethodsBehavioral analysis was used to evaluate the establishing of acute and chronic itch mice model, and to test the effects of different drugs or agents on mice itch behavior. Western blotting analysis was used to test the effect of agmatine on phosphorylation of ERK (p-ERK) expression in the spinal cord. Patch clamp recording was used to determine the effect agmatine on the excitability of DRG neurons and the role of ASIC3. Finally, the metabonomics analysis was performed to detect the concentration of agmatine in the affected skin under atopic dermatitis or psoriasis conditions.ResultsWe fused a mouse model and found that an intradermal injection of agmatine (an endogenous polyamine) into the nape of the neck or cheek induced histamine-independent scratching behavior in a dose-dependent manner. In addition, the ablation of nociceptive C-fibers by resiniferatoxin (RTX) abolished agmatine-induced scratching behavior. However, agmatine-induced itch was not affected by the pharmacological inhibition of either transient receptor potential vanilloid 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1); similar results were obtained from TRPV1−/− or TRPA1−/− mice. Furthermore, agmatine-induced itch was significantly suppressed by the administration of acid-sensing ion channel 3 (ASIC3) inhibitors, APETx2 or amiloride. Agmatine also induced the upregulation of p-ERK in the spinal cord; this effect was inhibited by amiloride. Current clamp recording showed that the acute perfusion of agmatine reduced the rheobase and increased the number of evoked action potentials in acute dissociated dorsal root ganglion (DRG) neurons while amiloride reversed agmatine-induced neuronal hyperexcitability. Finally, we identified significantly higher levels of agmatine in the affected skin of a mouse model of atopic dermatitis (AD) when compared to controls, and the scratching behavior of AD mice was significantly attenuated by blocking ASIC3.DiscussionCollectively, these results provide evidence that agmatine is a novel mediator of itch and induces itch via the activation of ASIC3. Targeting neuronal ASIC3 signaling may represent a novel strategy for the treatment of itch.
Central obesity as assessed by conicity index and a-body shape index associates with cardiovascular risk factors and mortality in kidney failure patients
Authors: Ryu Kakei , Suliman Mohamed E. , Qureshi Abdul Rashid , Chen Zhimin , Avesani Carla Maria , Brismar Torkel B. , Ripsweden Jonaz , Barany Peter , Heimbürger Olof , Stenvinkel Peter , Lindholm Bengt 
Published: March 2023

BackgroundAnthropometric indices of central obesity, waist circumference (WC), conicity index (CI), and a-body shape index (ABSI), are prognostic indicators of cardiovascular (CV) risk. The association of CI and ABSI with other CV risk indices, markers of nutritional status and inflammation, and clinical outcomes in chronic kidney disease (CKD) stage 5 (CKD5) patients was investigated.MethodsIn a cross-sectional study with longitudinal follow up of 203 clinically stable patients with CKD5 (median age 56 years; 68% males, 17% diabetics, 22% with CV disease, and 39% malnourished), we investigated CI and ABSI and their associations with atherogenic index of plasma (AIP), Framingham CV risk score (FRS), Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC), handgrip strength (HGS), high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). CV events (CVE) and all-cause mortality during up to 10-years follow up were analyzed by multivariate survival analysis of restricted mean survival time (RMST).ResultsChronic kidney disease patients with middle and highest CI and ABSI tertiles (indicating greater abdominal fat deposition), compared to those with the lowest CI and ABSI tertiles, tended to be older, more often men and diabetic, had significantly higher levels of hsCRP, IL-6, AIP, FRS, CAC and AVC scores. CI and ABSI were positively correlated with CAC, FRS, AIP, hsCRP and IL-6. Both CI and ABSI were negatively correlated with HGS. In age-weighted survival analysis, higher CI and ABSI were associated with higher risk of CVE (Wald test = 4.92, p = 0.027; Wald test = 4.95, p = 0.026, respectively) and all-cause mortality (Wald test = 5.24, p = 0.022; Wald test = 5.19, p = 0.023, respectively). In RMST analysis, low vs. high and middle tertiles of CI and ABSI associated with prolonged CVE-free time and death-free time, and these differences between groups increased over time.ConclusionAbdominal fat deposit indices, CI and ABSI, predicted CV outcomes and all-cause mortality, and were significantly associated with the inflammatory status in CKD patients.