bluuebunny/crossref_metadata_2025_split huggingface dataset:
Old age promotes retinal fibrosis in choroidal neovascularization through circulating fibrocytes and profibrotic macrophages
Authors: Yi Caijiao , Liu Jian , Deng Wen , Luo Chang , Qi Jinyan , Chen Mei , Xu Heping 
Published: February 2023

Abstract
Background
Retinal fibrosis affects 40–70% of neovascular age-related macular degeneration patients. This study investigated the effect of ageing on subretinal fibrosis secondary to choroidal neovascularization and the mechanism of action.

Methods
Subretinal fibrosis was induced in young (2.5-month) and aged (15–16-month) C57BL/6J mice using the two-stage laser protocol. Five and 30 days later, eyes were collected and stained for CD45 and collagen-1 and observed by confocal microscopy. Fibrocytes (CD45+collagen-1+) were detected in the bone marrow (BM), blood and fibrotic lesions by flow cytometry and confocal microscopy, respectively. BM-derived macrophages (BMDMs) were cultured from young and aged mice with or without TGF-β1 (10 ng/mL) treatment. The expression of mesenchymal marker αSMA (Acta2), fibronectin (Fn1) and collagen-1 (Col1a1) was examined by qPCR and immunocytochemistry, whereas cytokine/chemokine production was measured using the Luminex multiplex cytokine assay. BM were transplanted from 22-month (Ly5.2) aged mice into 2.5-month (Ly5.1) young mice and vice versa. Six weeks later, subretinal fibrosis was induced in recipient mice and eyes were collected for evaluation of fibrotic lesion size.

Results
Under normal conditions, the number of circulating fibrocytes (CD45+collagen-1+) and the expression levels of Tgfb1, Col1a1, Acta2 and Fn1 in BMDMs were significantly higher in aged mice compared to young mice. Induction of subretinal fibrosis significantly increased the number of circulating fibrocytes, enhanced the expression of Col1a1, Acta2 and Fn1 and the production of soluble urokinase plasminogen activator surface receptor (suPAR) but decreased the production of CXCL10 in BMDMs. BMDMs from aged subretinal fibrosis mice produced significantly higher levels of VEGF, angiopoietin-2 and osteopontin than cells from young subretinal fibrosis mice. The subretinal fibrotic lesion in 15–16-month aged mice was 62% larger than that in 2.5-month young mice. The lesion in aged mice contained a significantly higher number of fibrocytes compared to that in young mice. The number of circulating fibrocytes positively correlated with the size of subretinal fibrotic lesion. Transplantation of BM from aged mice significantly increased subretinal fibrosis in young mice.

Conclusions
A retina–BM–blood–retina pathway of fibrocyte/macrophage recruitment exists during retinal injury. Ageing promotes subretinal fibrosis through higher numbers of circulating fibrocytes and profibrotic potential of BM-derived macrophages.
Carotid body paraganglioma metastatic to spine causing cord compression: a case report
Authors: Tabb Jazmyne N. , Maas Jared A. , Earla Bhargav P. , Fallon Kenneth B. , McDonald Andrew M. , Dobelbower Michael C. 
Published: February 2023

Abstract
Background
Carotid body tumors (CBTs) are rare neuroendocrine neoplasms arising near the carotid bifurcation with a reported incidence of 1 to 2 cases in 100,000 patients. Most CBTs are sporadic, benign, slow-growing, and non-secreting, but untreated CBTs can grow locally to compress the nearby blood vessels, esophagus, and airway. Regional metastases can occur in 5% to 10% of cases, but distant metastases are exceedingly rare, occurring in roughly 1–2% of cases. As such, the optimal treatment for metastatic CBTs is not well-defined. We report a rare case of a patient with CBT distant metastases causing spinal cord compression.

Case presentation
A 40-year-old African American female presented with a right neck mass, headaches, vertigo, tinnitus, hoarseness, and dysphagia. Imaging demonstrated a Shamblin II right neck mass; subsequent transcervical resection and pathology showed a carotid body paraganglioma. The patient recurred locally near the carotid bifurcation, so she underwent Stereotactic Body Radiation Therapy to the recurrent right neck disease. She later re-presented with new onset bilateral lower extremity weakness, dysmetria, and numbness. She was found to have metastatic disease to the thoracic spine causing spinal cord compression. She underwent laminectomy, tumor resection, and posterior fixation followed by adjuvant radiation therapy. She was started on systemic therapy with sunitinib. She eventually progressed with metastatic disease to the right iliac bone, which was treated with palliative radiotherapy. Second line systemic therapy with capecitabine and temozolomide was started. At last follow up, the patient was asymptomatic with stable persistent disease.

Conclusions
Paragangliomas often exhibit a prolonged interval to the development of progression; locoregional recurrences or rare distant metastases have been reported to occur as many as 20 years from diagnosis. The natural course of CBTs in other cases as well as the present case call into question the idea that CBTs are truly benign; instead CBTs may be indolent tumors with metastatic potential. Treatment choices for CBTs include surgical resection, radiation therapy, and systemic therapy, though the optimal treatment regimen for metastatic CBTs is not well-defined. A more advanced understanding of CBT pathophysiology, disease classification, risk stratification, and treatment options is needed to improve outcomes for patients.
A randomized, double-blind trial comparing the effect of two blood pressure targets on global brain metabolism after out-of-hospital cardiac arrest
Authors: Mølstrøm Simon , Nielsen Troels Halfeld , Nordstrøm Carl-Henrik , Forsse Axel , Møller Søren , Venø Søren , Mamaev Dmitry , Tencer Tomas , Theódórsdóttir Ásta , Krøigård Thomas , Møller Jacob , Hassager Christian , Kjærgaard Jesper , Schmidt Henrik , Toft Palle 
Published: February 2023

Abstract
Purpose
This study aimed to assess the effect of different blood pressure levels on global cerebral metabolism in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA).

Methods
In a double-blinded trial, we randomly assigned 60 comatose patients following OHCA to low (63 mmHg) or high (77 mmHg) mean arterial blood pressure (MAP). The trial was a sub-study in the Blood Pressure and Oxygenation Targets after Out-of-Hospital Cardiac Arrest-trial (BOX). Global cerebral metabolism utilizing jugular bulb microdialysis (JBM) and cerebral oxygenation (rSO2) was monitored continuously for 96 h. The lactate-to-pyruvate (LP) ratio is a marker of cellular redox status and increases during deficient oxygen delivery (ischemia, hypoxia) and mitochondrial dysfunction. The primary outcome was to compare time-averaged means of cerebral energy metabolites between MAP groups during post-resuscitation care. Secondary outcomes included metabolic patterns of cerebral ischemia, rSO2, plasma neuron-specific enolase level at 48 h and neurological outcome at hospital discharge (cerebral performance category).

Results
We found a clear separation in MAP between the groups (15 mmHg, p < 0.001). Cerebral biochemical variables were not significantly different between MAP groups (LPR low MAP 19 (16–31) vs. high MAP 23 (16–33), p = 0.64). However, the LP ratio remained high (> 16) in both groups during the first 30 h. During the first 24 h, cerebral lactate > 2.5 mM, pyruvate levels > 110 µM, LP ratio > 30, and glycerol > 260 µM were highly predictive for poor neurological outcome and death with AUC 0.80. The median (IQR) rSO2 during the first 48 h was 69.5% (62.0–75.0%) in the low MAP group and 69.0% (61.3–75.5%) in the high MAP group, p = 0.16.

Conclusions
Among comatose patients resuscitated from OHCA, targeting a higher MAP 180 min after ROSC did not significantly improve cerebral energy metabolism within 96 h of post-resuscitation care. Patients with a poor clinical outcome exhibited significantly worse biochemical patterns, probably illustrating that insufficient tissue oxygenation and recirculation during the initial hours after ROSC were essential factors determining neurological outcome.
Using protein-per-mRNA differences among human tissues in codon optimization
Authors: Hernandez-Alias Xavier , Benisty Hannah , Radusky Leandro G. , Serrano Luis , Schaefer Martin H. 
Published: February 2023

Abstract
Background
Codon usage and nucleotide composition of coding sequences have profound effects on protein expression. However, while it is recognized that different tissues have distinct tRNA profiles and codon usages in their transcriptomes, the effect of tissue-specific codon optimality on protein synthesis remains elusive.

Results
We leverage existing state-of-the-art transcriptomics and proteomics datasets from the GTEx project and the Human Protein Atlas to compute the protein-to-mRNA ratios of 36 human tissues. Using this as a proxy of translational efficiency, we build a machine learning model that identifies codons enriched or depleted in specific tissues. We detect two clusters of tissues with an opposite pattern of codon preferences. We then use these identified patterns for the development of CUSTOM, a codon optimizer algorithm which suggests a synonymous codon design in order to optimize protein production in a tissue-specific manner. In human cell-line models, we provide evidence that codon optimization should take into account particularities of the translational machinery of the tissues in which the target proteins are expressed and that our approach can design genes with tissue-optimized expression profiles.

Conclusions
We provide proof-of-concept evidence that codon preferences exist in tissue-specific protein synthesis and demonstrate its application to synthetic gene design. We show that CUSTOM can be of benefit in biological and biotechnological applications, such as in the design of tissue-targeted therapies and vaccines.
Listening to music during a repeated sprint test improves performance and psychophysiological responses in healthy and physically active male adults
Authors: Jebabli Nidhal , Ben Aabderrahman Abderraouf , Boullosa Daniel , Chtourou Hamdi , Ouerghi Nejmeddine , Rhibi Fatma , Govindasamy Karuppasamy , Saeidi Ayoub , Clark Cain C. T. , Granacher Urs , Zouhal Hassane 
Published: February 2023

Abstract
Background
It is well-documented that listening to music has the potential to improve physical performance during intense physical exercise. Less information is available on the timing of music application. This study aimed to investigate the effects of listening to preferred music during the warm up of a subsequent test or during the test on performance of repeated sprint sets (RSS) in adult males.

Methods
In a randomized cross-over design, 19 healthy males (age, 22.1 ± 1.2 years; body mass, 72.7 ± 9.3 kg; height, 1.79 ± 0.06 m; BMI, 22.6 ± 2.2 kg m−2) performed a test including 2 sets of 5*20-m repeated-sprints under one of three conditions: listening to preferred music during the test; listening to preferred music during the warm-up; or not listening to music. The assessed parameters comprised RSS performance indices, blood lactate, heart rate, the pacing strategy profile, rating of perceived exertion, and a feeling scale.

Results
For performance indices during set 1 of the RSS test, we found a significant decrease in total sum sequence, fast time index and fatigue index in the listening to preferred music condition compared to the no music condition (total sum sequence: p = 0.006, d = 0.93; fast time index: p = 0.003, d = 0.67; fatigue index: p < 0.001; d = 1.30) and the listening to preferred music during the warm-up condition (fast time index: p = 0.002; d = 1.15; fatigue index: p = 0.006; d = 0.74). However, there was no significant effect of listening to preferred music on physical performance during set 2 of the RSS test. Compared to the no music condition, blood lactate concentrations were higher in the listening to preferred music during the test condition (p = 0.025; d = 0.92). In addition, listening to preferred music appears not to have an effect on heart rate, the pacing strategy profile, perceived exertion, and affective responses before, during and after the RSS test.

Conclusion
Findings from this study revealed that RSS performances were better (FT and FI indices) in the PMDT compared with the PMWU condition. Moreover, in set 1 of the RSS test, better RSS indices were found in the PMDT compared to NM condition.
Sex differences in friendships and loneliness in autistic and non-autistic children across development
Authors: Libster Natalie , Knox Azia , Engin Selin , Geschwind Daniel , Parish-Morris Julia , Kasari Connie 
Published: February 2023

Abstract
Background
Autistic children have been shown to have less complete definitions of friendships and higher levels of loneliness than their non-autistic peers. However, no known studies have explored sex differences in autistic children’s understanding of friendships and reported loneliness across development. Autistic girls demonstrate higher levels of social motivation than autistic boys and appear to “fit in” with their peers, but they often have difficulty recognizing reciprocal friendships during middle childhood. As autistic girls develop a more complex understanding of friendship during adolescence, they may begin to redefine their friendships and experience heightened loneliness. Here, we explored how autistic and non-autistic boys and girls define the meaning of friendship and report feelings of loneliness across development. We also examined their perceptions of friendships and loneliness.

Methods
This mixed-methods study analyzed the transcribed clinical evaluations of 58 autistic children (29 girls) matched to 42 non-autistic children (21 girls) on age and IQ. Transcripts were coded for four categories that children used to define friendships—personality, companionship, dependability, and intimacy—and for reported loneliness. We then compared these codes across diagnosis, sex, and age. Content analyses were further implemented to gain a more holistic understanding of children’s perceptions of friendships and loneliness.

Results
Girls, regardless of diagnosis, were more likely than boys to refer to personality when defining the meaning of friendship, and the likelihood of referring to dependability and intimacy increased with age. Most children reported having at least one friend, though some autistic adolescents reported not having friends or were uncertain whether they had friends. While autistic and non-autistic boys and girls were equally likely to report feeling lonely at times, several autistic girls and boys reported being frequently lonely.

Limitations
This study was a secondary data analysis. The standardized set of questions on the ADOS limited the amount of information that children provided about their friendships and perceptions of loneliness.

Conclusion
As with non-autistic children, autistic children acquire a more complex understanding of friendship throughout development. However, as children begin to prioritize dependability and intimacy in friendships, autistic adolescents may have difficulty developing friendships characterized by these constructs. Furthermore, the quantity and/or quality of autistic children’s friendships may not be sufficient to alleviate loneliness.
Cerebellar hematoma in severe hemophilia with inhibitor on emicizumab prophylaxis: a case report
Authors: Albattat Sami , Alabdultaif Abbas , Albattat Fatimah , Albattat Batla 
Published: February 2023

Abstract
Background
Emicizumab is a novel prophylactic medication used to treat patients with hemophilia A. It is indicated to minimize the frequency of bleeding episodes and the severity of serious bleeding in patients with hemophilia A utilizing inhibitors. However, some cases of bleeding episodes have been reported, and more data are needed regarding their management and expected outcomes.

Case presentation
We report a case of a 4-year-old Saudi Arabian boy with severe hemophilia A who presented with a post-traumatic cerebral hemorrhage. The patient, with high titer inhibitors, was on emicizumab prophylaxis therapy. On hospital admission, he received tranexamic acid (10 mg intravenously, every 6 hours), and recombinant activated factor VII 120 µg/kg every 2 hours for 2 days then every 4 hours for 4 days. On follow-up, the patient showed no signs of neurological deficit. There was no need for emergency neurosurgical intervention since the bleeding had been controlled throughout the first 2 days. There were no recorded thrombotic sequelae or neurological complications, with complete resolution within 10 days.

Conclusions
This case implies that low-dose recombinant activated factor VII might be used safely and effectively with patients with hemophilia A on emicizumab prophylaxis, to reduce the risk of cerebral hemorrhage or another episode of serious bleeding along with its long-term complications.
Existence and multiplicity of solutions for three-point boundary value problems with instantaneous and noninstantaneous impulses
Authors: Yao Wangjin 
Published: February 2023

AbstractIn this paper, three-point boundary value problems for second-orderp-Laplacian differential equations with instantaneous and noninstantaneous impulses are studied. The existence of at least one classical solution and infinitely many classical solutions is obtained by using variational methods and critical point theory. In addition, some examples are given to illustrate our main results.
The reproduction rate of severe acute respiratory syndrome coronavirus 2 different variants recently circulated in human: a narrative review
Authors: Karimizadeh Zahra , Dowran Razieh , Mokhtari-azad Talat , Shafiei-Jandaghi Nazanin-Zahra 
Published: February 2023

AbstractSARS-COV-2 is responsible for the current worldwide pandemic, which started on December 2019 in Wuhan, China. On March 2020 World Health Organization announced COVID-19 as the new pandemic. Some SARS-COV-2 variants have increased transmissibility, cause more severe disease (e.g., increased hospitalizations or deaths), are resistant to antibodies produced by the previous infection or vaccination, and there is more difficulty in treatment and diagnosis of them. World Health Organization considered them as SARS-CoV-2 variants of concern. The introductory reproduction rate (R0) is an epidemiologic index of the transmissibility of the virus, defined as the average number of persons infected by the virus after known contact with an infectious person in a susceptible population. An R0 > 1 means that the virus is spreading exponentially, and R0 < 1, means that the outbreak is subsiding. In various studies, the estimated R and VOC growth rates were reported to be greater than the ancestral strains. However, it was also a low level of concordance between the estimated Rt of the same variant in different studies. It is because the R of a variant not only dependent on the biological and intrinsic factors of the virus but also several parameters can affect the R0, including the duration of contagiousness and the likelihood of infection per contact. Evaluation of changes in SARS-CoV-2 has shown that the rate of human-to-human transmission of this virus has increased. Like other viruses with non-human sources which succeeded in surviving in the human population, SARS-CoV-2 has gradually adapted to the human population, and its ability to transmit from human to human has increased. Of course, due to the continuous changes in this virus, it is crucial to survey the rate of transmission of the virus over time.
Pharmacovigilance-based drug repurposing: searching for putative drugs with hypohidrosis or anhidrosis adverse events for use against hyperhidrosis
Authors: Liu Yi , Liu Yanguo , Fan Rongrong , Kehriman Nurmuhammat , Zhang Xiaohong , Zhao Bin , Huang Lin 
Published: February 2023

Abstract
Background
Drug repurposing refers to the application of existing drugs to new therapeutic indications. As phenotypic indicators of human drug response, drug side effects may provide direct signals and unique opportunities for drug repurposing.

Objectives
We aimed to identify drugs frequently associated with hypohidrosis or anhidrosis adverse reactions (that is, the opposite condition of hyperhidrosis) from the pharmacovigilance database, which could be potential candidates as anti-hyperhidrosis treatment agents.

Methods
In this observational, retrospective, pharmacovigilance study, adverse event reports of hypohidrosis or anhidrosis in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) were assessed between January 2004 and December 2021 using reporting odds ratio (ROR) estimates and categorized by the World Health Organization Anatomical Therapeutic Chemical (ATC) classification code. The onset time of drug-associated hypohidrosis or anhidrosis was also examined.

Results
There were 540 reports of 192 drugs with suspected drug-associated hypohidrosis or anhidrosis in the FAERS database, of which 39 drugs were found to have statistically significant signals. Nervous system drugs were most frequently reported (187 cases, 55.82%), followed by alimentary tract and metabolism drugs (35 cases, 10.45%), genitourinary system and sex hormones (28 cases, 8.36%), and dermatologicals (22 cases, 6.57%). The top 3 drug subclasses were antiepileptics, drugs for urinary frequency and incontinence, and antidepressants. Taking disproportionality signals, pharmacological characteristics of drugs and appropriate onset time into consideration, the main putative drugs for hyperhidrosis were glycopyrronium, solifenacin, oxybutynin, and botulinum toxin type A. Other drugs, such as topiramate, zonisamide, agalsidase beta, finasteride, metformin, lamotrigine, citalopram, ciprofloxacin, bupropion, duloxetine, aripiprazole, prednisolone, and risperidone need more investigation.

Conclusions
Several candidate agents among hypohidrosis or anhidrosis-related drugs were identified that may be redirected for diminishing sweat production. There are affirmative data for some candidate drugs, and the remaining proposed candidate drugs without already known sweat reduction mechanisms of action should be further explored.
Early identification and treatment for peripheral arterial disease in patients with ischemic cerebrovascular disease
Authors: Li Lu-guang , Ma Xin 
Published: February 2023

AbstractIschemic cerebrovascular disease (ICVD) is a major cause of mortality and disability worldwide and is often caused by atherosclerosis. As a systemic disease, atherosclerosis usually affects multiple vascular beds, mainly including cerebral, coronary, and peripheral arteries. Therefore, ICVD is easily complicated by lower-extremity peripheral arterial disease (PAD). ICVD patients with PAD have more serious symptoms and a worse prognosis, however, neurologists might neglect the evaluation and management of the coexistent PAD, and there is still a lack of consensuses about the diagnosis and treatment for such patients. By summarizing relevant research progresses, this review showed that duplex ultrasound had more advantages in the early screening and evaluation of PAD in ICVD patients among multiple methods to diagnose PAD. Furthermore, the current evidence seems to support that single-drug antiplatelet can be used as the basic treatment, and new antithrombotic strategies, such as ticagrelor only or aspirin combined with low-dose rivaroxaban are expected to further reduce the incidence of stroke for ICVD patients with PAD. More effective treatments would be explored by large-scale trials to guide the clinical management to prevent secondary stroke for such patients.