bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Globular Cells in Corneal Nerve Vortex
Authors: Hao Ran , Liu Ziyuan , Chou Yilin , Huang Chen , Jing Dalan , Wang Haikun , Gao Shuang , Li Xuemin 
Published: February 2022

PurposeLess was known about globular cells which were a type of dendritic cells (DCs) in cornea. We aimed to investigate the morphological and distribution characteristics of globular cells in corneal vortex and their clinical correlations with ocular surface.MethodsCase records of patients who underwent in vivo confocal microscopy (IVCM) were evaluated retrospectively. The morphology and distribution features of globular cells in cornea nerve vortex and their co-existence status with Langerhans cells (LCs) were analyzed. Data of ocular surface symptoms and signs were collected and their correlations with globular cells distribution patterns and dendritic forms were performed. Dry eye patients without LCs were treated with preservative-free artificial tears, while patients with LCs were treated with artificial tears and fluoromethalone until the activated LCs disappeared.ResultsA total of 836 eyes from 451 individuals were included. Three distribution patterns of globular cells in vortex were investigated, type 1 scattered globular cells (57.66%), type 2 large amounts of globular cells (≥50 cells) gathering in vortex and along some fixed vortex direction horizontally (13.52%) and type 3 no globular cells (28.83%). Their location and cell count altered slightly in the follow-ups but would not disappear. LCs could co-exist with globular cells and could fade after treatment. The type 2 distribution pattern was associated with older age (p = 0.000) and higher upper eyelid Meiboscore (p = 0.006). Dendritic globular cells had higher Meiboscore than Non-dendritic forms.ConclusionsGlobular cells had characteristic distribution patterns and biological features different from LCs. They were associated with long-term irritation of the meibomian gland dysfunction.
Prospective Studies on the Risk of Rheumatoid Arthritis: The European Risk RA Registry
Authors: Studenic Paul , Hensvold Aase , Kleyer Arnd , van der Helm-van Mil Annette , Pratt Arthur G. , Sieghart Daniela , Krönke Gerhard , Williams Ruth , de Souza Savia , Karlfeldt Susanne , Johannesson Martina , Krogh Niels Steen , Klareskog Lars , Catrina Anca I. 
Published: February 2022

BackgroundThe accumulation of risk for the development of rheumatoid arthritis (RA) is regarded as a continuum that may start with interacting environmental and genetic factors, proceed with the initiation of autoimmunity, and result in the formation of autoantibodies such as anti-citrullinated peptide antibodies (ACPA). In parallel, at-risk individuals may be asymptomatic or experience joint pain (arthralgia) that is itself non-specific or clinically suspicious for evolving RA, even in the absence of overt arthritis. Optimal strategies for the management of people at-risk of RA, both for symptom control and to delay or prevent progression to classifiable disease, remain poorly understood.MethodsTo help address this, groups of stakeholders from academia, clinical rheumatology, industry and patient research partners have collaborated to advance understanding, define and study different phases of the at-risk state. In this current report we describe different European initiatives in the field and the successful effort to build a European Registry of at-risk people to facilitate observational and interventional research.ResultsWe outline similarities and differences between cohorts of at-risk individuals at institutions spanning several countries, and how to best combine them within the new database. Over the past 2 years, besides building the technical infrastructure, we have agreed on a core set of variables that all partners should strive to collect for harmonization purposes.ConclusionWe emphasize to address this process from different angles and touch on the biologic, epidemiologic, analytic, and regulatory aspects of collaborative studies within a meta-database of people at-risk of RA.
Convergent and Divergent Structural Connectivity of Brain White Matter Network Between Patients With Erectile Dysfunction and Premature Ejaculation: A Graph Theory Analysis Study
Authors: Zhang Tielong , Yuan Peng , Cui Yonghua , Yuan Weibiao , Jiang Daye 
Published: February 2022

BackgroundSexual dysfunction, namely, erectile dysfunction (ED) and premature ejaculation (PE), has been found to be associated with abnormal structural connectivity in the brain. Previous studies have mainly focused on a single disorder, however, convergent and divergent structural connectivity patterns of the brain network between ED and PE remain poorly understood.MethodsT1-weighted structural data and diffusion tensor imaging data of 28 patients with psychological ED, 28 patients with lifelong PE (LPE), and 28 healthy controls (HCs) were obtained to map the white matter (WM) brain networks. Then, the graph-theoretical method was applied to investigate the differences of network properties (small-world measures) of the WM network between patients with ED and LPE. Furthermore, nodal segregative and integrative parameters (nodal clustering coefficient and characteristic path length) were also explored between these patients.ResultsSmall-world architecture of the brain networks were identified for both psychological ED and LPE groups. However, patients with ED exhibited increased average characteristic path length of the brain network when compared with patients with LPE and HCs. No significant difference was found in the average characteristic path length between patients with LPE and HCs. Moreover, increased nodal characteristic path length was found in the right middle frontal gyrus (orbital part) of patients with ED and LPE when compared with HCs. In addition, patients with ED had increased nodal characteristic path length in the right middle frontal gyrus (orbital part) when compared with patients with LPE.ConclusionTogether, our results demonstrated that decreased integration of the right middle frontal gyrus (orbital part) might be a convergent neuropathological basis for both psychological ED and LPE. In addition, patients with ED also exhibited decreased integration in the whole WM brain network, which was not found in patients with LPE. Therefore, altered integration of the whole brain network might be the divergent structural connectivity patterns for psychological ED and LPE.
Clinical, Neurophysiological, Radiological, Pathological, and Genetic Features of Dysferlinopathy in Saudi Arabia
Authors: Alharbi Norah , Matar Rawan , Cupler Edward , Al-Hindi Hindi , Murad Hatem , Alhomud Iftteah , Monies Dorota , Alshehri Ali , Alyahya Mossaed , Meyer Brian , Bohlega Saeed 
Published: February 2022

BackgroundTo characterize the phenotypic, neurophysiological, radiological, pathological, and genetic profile of 33 Saudi Arabian families with dysferlinopathy.MethodsA descriptive observational study was done on a cohort of 112 Saudi Arabian families with LGMD. Screening for the Dysferlin (DYSF) gene was done in a tertiary care referral hospital in Saudi Arabia. Clinical, Neurophysiological, Radiological, Pathological, and Genetic findings in subjects with dysferlin mutation were the primary outcome variables. Statistical analysis was done by Epi-info.Results33 out of 112 families (29.46%) registered in the LGMD cohort had Dysferlinopathy. 53 subjects (28 males, 52.83%) from 33 families were followed up for various periods ranging from 1 to 28 years. The mean age of onset was 17.79 ± 3.48 years (Range 10 to 25 years). Miyoshi Myopathy phenotype was observed in 50.94% (27 out of 53), LGMDR2 phenotype in 30.19% (16 out of 53), and proximodistal phenotype in 15.09% (8 out of 53) of the subjects. Loss of ambulation was observed in 39.62% (21 out of 53 subjects). Electrophysiological, Radiological, and histopathological changes were compatible with the diagnosis. Mean serum Creatinine Kinase was 6,464.45 ± 4,149.24 with a range from 302 to 21,483 IU/L. In addition, 13 dysferlin mutations were identified two of them were compound heterozygous. One founder mutation was observed c.164_165insA in 19 unrelated families.ConclusionThe prevalence of Dysferlinopathy was 29.46% in the native Saudi LGMD cohort. It is the most prevalent subtype seconded by calpainopathy. The clinical course varied among the study subjects and was consistent with those reported from different ethnic groups. One founder mutation was identified. Initial screening of the founder mutations in new families is highly recommended.
Serum Uric Acid Levels at Admission Could Predict the Chronic Post-stroke Fatigue
Authors: Ren Wenwei , Wu Junxin , Wu Zijing , Yang Shuang , Jiang Xiaofang , Xu Minjie , Wu Beilan , Xie Caixia , He Jincai , Yu Xin 
Published: February 2022

BackgroundPost-stroke fatigue (PSF) is a frequent complication of stroke. Serum uric acid (SUA) is frequently thought to be a risk factor for stroke. This study aimed to investigate whether SUA also played a role in PSF.MethodsSubjects with ischemic stroke were screened from The First Affiliated Hospital of Wenzhou Medical University between January 2020 and October 2020. Patients' fatigue symptoms were assessed by the Fatigue severity scale (FSS). To investigate the relationship between SUA and PSF, binary logistic regression analysis was conducted, with the confounders being controlled. SUA levels were divided into four layers (Q1 ≤ 245 μmol/L; Q2 246–308 μmol/L; Q3 309–365 μmol/L; Q4 ≥366 μmol/L) based on the quartiles.ResultsSUA levels were significantly higher in the PSF group (345.96 ± 73.78 μmol/L) than the non-PSF group (295.97 ± 87.8 μmol/L, P &lt; 0.001). There were no differences in any other variables between these two groups. After adjusting the confounders, the risk of PSF in the Q4 layer (≥366 μmol/L) was 6.05 times (95% CI 1.79–20.43, P = 0.004) higher than that in Q1 (≤245 μmol/L).ConclusionHigh SUA at admission was an independent risk factor for fatigue 1 year after stroke onset. High SUA (≥366 μmol/L) during stroke deserves more attention, and active control of high SUA levels may be beneficial to reduce the incidence of PSF in the chronic stage following stroke.
Metformin Alleviates Endometriosis and Potentiates Endometrial Receptivity via Decreasing VEGF and MMP9 and Increasing Leukemia Inhibitor Factor and HOXA10
Authors: Cheng Jing , Li Chunyang , Ying Yingfen , Lv Jieqiang , Qu Xianqin , McGowan Eileen , Lin Yiguang , Zhu Xueqiong 
Published: February 2022

Background: Endometriosis affects endometrial receptivity, a key factor for successful embryo implantation. Metformin treatment is associated with alleviating the symptoms of endometriosis; however the mechanism of metformin action is unclear. Neoangiogenesis plays an important role in the development and recurrence of endometriosis. In addition, the leukemia inhibitor factor (LIF) and HOXA10 genes are also distinguishing markers of endometriosis (decrease) and endometrial receptivity (increase). This study investigated the therapeutic potentials of metformin and the underlying mechanism using an in vivo rat endometriosis model.Methods: Female Wistar albino mature rats with experimentally induced endometriosis were used in this study. Metformin was administered at doses of 100 mg/kg/d and 200 mg/kg/d. The volume of endometriotic implants was assessed. The protein and mRNA expression of the vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), the endometrial receptivity markers, LIF and HOXA10, were measured in the endometrium of rats with endometriosis.Results: Metformin treatment significantly suppressed the growth of endometriotic implants. Further, the expression of VEGF and MMP-9 protein and mRNA in endometriotic implants were significantly reduced. Metformin also significantly upregulated LIF and HOXA10 expression in endometrium from rats with endometriosis. The inhibitory effect of metformin on the growth of endometriotic implants, VEGF and MMP-9, and upregulating effect on LIF and HOXA10, was optimal at a dose of 100 mg/kg/d.Conclusion: Our in vivo data demonstrates that metformin treatment alleviates endometriosis and potentiates endometrial receptivity. The underlying mechanisms are associated with decreased expression of VEGF and MMP-9 genes and upregulation of the LIF and HOXA10 genes. The effect of metformin was optimal at 100 mg/kg/d. These findings provide a potential alternative for women with endometriosis with the potential to increase fertility. Metformin is an approved drug by FDA for diabetes and this study may add another potential clinical use for metformin.
Adapalene Inhibits Prostate Cancer Cell Proliferation In Vitro and In Vivo by Inducing DNA Damage, S-phase Cell Cycle Arrest, and Apoptosis
Authors: Nong Hai-bin , Zhang Ya-nan , Bai Yi-guang , Zhang Qiong , Liu Ming-fu , Zhou Quan , Shi Zhuo-hua , Zeng Gao-feng , Zong Shao-Hui 
Published: February 2022

Aims: Prostate cancer is a well-known aggressive malignant tumor in men with a high metastasis rate and poor prognosis. Adapalene (ADA) is a third-generation synthetic retinoid with anticancer properties. We investigated the anti-tumor activity and molecular mechanisms of ADA in the RM-1 prostate cancer cell line in vivo and in vitro.Methods: The effects of ADA on cell proliferation were estimated using the CCK-8 and colony formation assays. The wound-healing assay and the Transwell assay were employed to examine the migratory capacity and invasiveness of the cells. Flow cytometry was utilized to evaluate the cell cycle and apoptosis, and Western blotting analysis was used to assess the expression of the associated proteins. Micro-CT, histomorphological, and immunohistochemical staining were used to assess the effects of ADA on bone tissue structure and tumor growth in a mouse model of prostate cancer bone metastasis.Result: ADA dramatically inhibited cell proliferation, migration, invasiveness, and induced S-phase arrest and apoptosis. ADA also regulated the expression of S-phase associated proteins and elevated the levels of DNA damage markers, p53, and p21 after ADA treatment, suggesting that the anti-tumor effect of ADA manifests through the DNA damage/p53 pathway. Furthermore, we observed that ADA could effectively inhibited tumor growth and bone destruction in mice.Conclusion: ADA inhibited prostate cancer cell proliferation, elicited apoptosis, and arrested the cell cycle in the S-phase. ADA also slowed the rate of tumor growth and bone destruction in vitro. Overall, our results suggest that ADA may be a potential treatment against prostate cancer.
Relationship Between Family Functioning and Medication Adherence in Chinese Patients With Mechanical Heart Valve Replacement: A Moderated Mediation Model
Authors: Ni Hong , Lin Yanjuan , Peng Yanchun , Li Sailan , Huang Xizhen , Chen Liangwan 
Published: February 2022

Background: Medication adherence is crucial for patients with mechanical heart valve replacement. Although families functioning is positively associated with medication adherence, little is known about the underlying mechanisms.Objective: To test whether family functioning affects medication adherence through illness perceptions and whether this mediating effect was moderated by medication literacy.Methods: 319 patients after mechanical heart valve replacement were included in this cross-sectional study from June 2021 to October 2021. Data regarding family functioning, illness perceptions, medication adherence, and medication literacy were collected through questionnaires. The moderated mediation model was examined by Hayes’s PROCESS macro, based on the bootstrapping method.Results: The results revealed illness perceptions partially mediated the association of family functioning on medication adherence [β = 0.08, 95% confidence intervals: (0.04, 0.12)], and this effect was stronger for patients with low medication literacy than those with high literacy [β = −0.36, 95% CI: (−0.50, −0.22)]. Furthermore, the relationship between family functioning and medication adherence was only significant in patients with low medication literacy [β= 0.36, 95% CI: (0.23, 0.50)].Conclusion: The mediating effect of illness perceptions between family functioning and medication adherence was moderated by medication literacy. Efforts to improve medication adherence by targeting at improving family functioning may be more effective when considering illness perceptions, especially for patients with limited medication literacy.
Metabolomic Impact of Lidocaine on a Triple Negative Breast Cancer Cell Line
Authors: Chamaraux-Tran Thiên-Nga , Muller Marie , Pottecher Julien , Diemunsch Pierre A. , Tomasetto Catherine , Namer Izzie-Jacques , Dali-Youcef Nassim 
Published: February 2022

Background: Metabolomics and onco-anesthesia are two emerging research fields in oncology. Metabolomics (metabolites analysis) is a new diagnostic and prognostic tool that can also be used for predicting the therapeutic or toxic responses to anticancer treatments. Onco-anesthesia studies assess the impact of anesthesia on disease-free and overall survival after cancer surgery. It has been shown that local anesthetics (LA), particularly lidocaine (LIDO), exert antitumor properties both in vitro and in vivo and may alter the biologic fingerprints of cancer cells. As LA are known to impair mitochondrial bioenergetics and byproducts, the aim of the present study was to assess the impact of LIDO on metabolomic profile of a breast cancer cell line.Methods: Breast cancer MDA-MB-231 cells were exposed for 4 h to 0.5 mM LIDO or vehicle (n = 4). The metabolomic fingerprint was characterized by high resolution magic angle spinning NMR spectroscopy (HRMAS). The multivariate technique using the Algorithm to Determine Expected Metabolite Level Alteration (ADEMA) (Cicek et al., PLoS Comput. Biol., 2013, 9, e1002859), based on mutual information to identify expected metabolite level changes with respect to a specific condition, was used to determine the metabolites variations caused by LIDO.Results: LIDO modulates cell metabolites levels. Several pathways, including glutaminolysis, choline, phosphocholine and total choline syntheses were significantly downregulated in the LIDO group.Discussion: This is the first study assessing the impact of LIDO on metabolomic fingerprint of breast cancer cells. Among pathways downregulated by LIDO, many metabolites are reported to be associated with adverse prognosis when present at a high titer in breast cancer patients. These results fit with the antitumor properties of LIDO and suggest its impact on metabolomics profile of cancer cells. These effects of LIDO are of clinical significance because it is widely used for local anesthesia with cutaneous infiltration during percutaneous tumor biopsy. Future in vitro and preclinical studies are necessary to assess whether metabolomics analysis requires modification of local anesthetic techniques during tumor biopsy.
Ayurveda-based Botanicals as Therapeutic Adjuvants in Paclitaxel-induced Myelosuppression
Authors: Saggam Akash , Kale Prathamesh , Shengule Sushant , Patil Dada , Gautam Manish , Tillu Girish , Joshi Kalpana , Gairola Sunil , Patwardhan Bhushan 
Published: February 2022

Chemotherapy-induced myelosuppression is one of the major challenges in cancer treatment. Ayurveda-based immunomodulatory botanicalsAsparagus racemosusWilld (AR/Shatavari) andWithania somnifera(L.). Dunal (WS/Ashwagandha) have potential role to manage myelosuppression. We have developed a method to study the effects of AR and WS as therapeutic adjuvants to counter paclitaxel (PTX)-induced myelosuppression. Sixty female BALB/c mice were divided into six groups—vehicle control (VC), PTX alone, PTX with aqueous and hydroalcoholic extracts of AR (ARA, ARH) and WS (WSA, WSH). The myelosuppression was induced in mice by intraperitoneal administration of PTX at 25 mg/kg dose for three consecutive days. The extracts were orally administered with a dose of 100 mg/kg for 15 days prior to the induction with PTX administration. The mice were observed daily for morbidity parameters and were bled from retro-orbital plexus after 2 days of PTX dosing. The morbidity parameters simulate clinical adverse effects of PTX that include activity (extreme tiredness due to fatigue), behavior (numbness and weakness due to peripheral neuropathy), body posture (pain in muscles and joints), fur aspect and huddling (hair loss). The collected samples were used for blood cell count analysis and cytokine profiling using Bio-Plex assay. The PTX alone group showed a reduction in total leukocyte and neutrophil counts (4,800 ± 606; 893 ± 82) when compared with a VC group (9,183 ± 1,043; 1,612 ± 100) respectively. Pre-administration of ARA, ARH, WSA, and WSH extracts normalized leukocyte counts (10,000 ± 707; 9,166 ± 1,076; 10,333 ± 1,189; 9,066 ± 697) and neutrophil counts (1,482 ± 61; 1,251 ± 71; 1,467 ± 121; 1,219 ± 134) respectively. Additionally, higher morbidity score in PTX group (7.4 ± 0.7) was significantly restricted by ARA (4.8 ± 1.1), ARH (5.1 ± 0.6), WSA (4.5 ± 0.7), and WSH (5 ± 0.8). (Data represented in mean ± SD). The extracts also significantly modulated 20 cytokines to evade PTX-induced leukopenia, neutropenia, and morbidity. The AR and WS extracts significantly prevented PTX-induced myelosuppression (p&lt; 0.0001) and morbidity signs (p&lt; 0.05) by modulating associated cytokines. The results indicate AR and WS as therapeutic adjuvants in cancer management.
Type D Personality and Big Five Personality Traits and the Risk of Breast Cancer: A Case-Control Study
Authors: Wojciechowska Irena , Matkowski Rafał , Pawłowski Tomasz 
Published: February 2022

ObjectiveThe goal of this study is to establish the differences in Type D personality and Big five personality traits between a group of newly diagnosed breast cancer patients and a group of controls.MethodsA comparative study of breast cancer patients and women without previous history of cancer was carried out. We used Type D Scale-14 as an instrument for the assessment of the type-D personality pattern and NEO-FFI for the assessment of the Big Five personality traits. Conditional logistic regression models were used to estimate odds ratios and 95% confidence intervals were applied for breast cancer by personality trait factors.ResultsNegative affectivity (NA) (OR = 4.45 95% CI: 1.96–10.61), neuroticism HIGH (OR = 3.97, 95% CI: 1.08–15.81), openness to experience HIGH (OR = 3.47 95% CI: 1.11–11.49), were associated factors significantly related to an increased risk of breast cancer, whereas Social Inhibition (SI) was associated factor with a decreased risk of breast cancer (OR = 0.40 95% CI: 0.16–0.92).ConclusionsThis was the first case-control study which analyzed NA and SI traits in breast cancer patients. SI as a breast-cancer risk decreasing factor might indicate that expressing negative emotions is not always a healthy mechanism of their regulation.