bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Dermcidin Protects Mice Against Hepatic Ischemia-Reperfusion–Induced Local and Remote Inflammatory Injury
Authors: Qiang Xiaoling , Li Jianhua , Zhu Shu , He Mingzhu , Chen Weiqiang , Al-Abed Yousef , Brenner Max , Tracey Kevin J. , Wang Ping , Wang Haichao 
Published: January 2022

BackgroundHepatic ischemia and reperfusion (I/R) injury is commonly associated with surgical liver resection or transplantation, and represents a major cause of liver damage and graft failure. Currently, there are no effective therapies to prevent hepatic I/R injury other than ischemic preconditioning and some preventative strategies. Previously, we have revealed the anti-inflammatory activity of a sweat gland-derived peptide, dermcidin (DCD), in macrophage/monocyte cultures. Here, we sought to explore its therapeutic potential and protective mechanisms in a murine model of hepatic I/R.MethodsMale C57BL/6 mice were subjected to hepatic ischemia by clamping the hepatic artery and portal vein for 60 min, which was then removed to initiate reperfusion. At the beginning of reperfusion, 0.2 ml saline control or solution of DCD (0.5 mg/kg BW) or DCD-C34S analog (0.25 or 0.5 mg/kg BW) containing a Cys (C)→Ser (S) substitution at residue 34 was injected via the internal jugular vein. For survival experiments, mice were subjected to additional resection to remove non-ischemic liver lobes, and animal survival was monitored for 10 days. For mechanistic studies, blood and tissue samples were collected at 24 h after the onset of reperfusion, and subjected to measurements of various markers of inflammation and tissue injury by real-time RT-PCR, immunoassays, and histological analysis.ResultsRecombinant DCD or DCD-C34S analog conferred a significant protection against lethal hepatic I/R when given intravenously at the beginning of reperfusion. This protection was associated with a significant reduction in hepatic injury, neutrophilic CXC chemokine (Mip-2) expression, neutrophil infiltration, and associated inflammation. Furthermore, the administration of DCD also resulted in a significant attenuation of remote lung inflammatory injury. Mechanistically, DCD interacted with epidermal growth factor receptor (EGFR), a key regulator of liver inflammation, and significantly inhibited hepatic I/R-induced phosphorylation of EGFR as well as a downstream signaling molecule, protein kinase B (AKT). The suppression of EGFR expression by transducing Egfr-specific shRNA plasmid into macrophages abrogated the DCD-mediated inhibition of nitric oxide (NO) production induced by a damage-associated molecular pattern (DAMP), cold-inducible RNA-binding protein, CIRP.ConclusionsThe present study suggests that human DCD and its analog may be developed as novel therapeutics to attenuate hepatic I/R-induced inflammatory injury possibly by impairing EGFR signaling.
Ocular Manifestations of Acute Secondary Angle Closure Associated With Lens Subluxation
Authors: Jing Qinghe , Chen Tianhui , Chen Zexu , Lan Lina , Zhao Chen , Jiang Yongxiang 
Published: January 2022

Purpose:To evaluate the clinical characteristics and ocular features of patients with acute secondary angle closure, associated with lens subluxation (ASAC-LS).Methods:We performed a retrospective study at the EENT Hospital of Fudan University, Shanghai, China. A total of 41 affected eyes from 41 patients were enrolled in this study. Furthermore, 20 affected eyes were part of the ASAC-LS cohort and 21 affected eyes were included in the acute primary angle closure (APAC) cohort. The best-corrected visual acuity (BCVA), intraocular pressure (IOP), axial length (AL), minimum corneal curvature (K1), maximum corneal curvature (K2), and anterior chamber depth (ACD) were measured and compared between the 2 cohorts. In addition, inter-eye (intraindividual) comparison was performed.Results:The ASAC-LS cohort exhibited younger ages, more frequent trauma history (35%), lower IOP (27.43 ± 13.86 mmHg vs. 41.27 ± 10.36 mmHg), longer AL (23.96 ± 2.60 vs. 22.49 ± 0.77 mm), shallower ACD (1.28 ± 0.38 vs. 1.58 ± 0.23 mm), and bigger ACD differences (0.99 ± 0.52 vs. 0.15 ± 0.19 mm), as compared with the APAC cohort (all p &lt; 0.05). Moreover, eyes from the lens subluxation cohort experienced worse BCVA, higher IOP, and shallower ACD than their matched unaffected eyes (all p &lt; 0.05). Although longer AL, shallower ACD, and bigger ACD differences were strongly correlated with lens subluxation in a univariate logistic regression analysis, only the ACD difference remained significant in the multivariate model (p = 0.004, OR = 1,510.50). Additionally, according to the receiver operating characteristic (ROC) curve analysis, both ACD and ACD differences had greater value in the differential diagnosis of ASAC-LS and APAC, with a cut-off value of 1.4 and 0.63 mm, respectively.Conclusions:Shallower ACD and larger ACD differences provide the promising diagnostic potential for patients with ASAC-LS.
Five-Minute Apgar Score and the Risk of Mental Disorders During the First Four Decades of Life: A Nationwide Registry-Based Cohort Study in Denmark
Authors: He Hua , Yu Yongfu , Wang Hui , Obel Carsten Lyng , Li Fei , Li Jiong 
Published: January 2022

Objectives:The associations of long-term risks of the full spectrum of mental disorders with clinically reassuring but suboptimal score range 7–9 remain unclear. This study investigated these associations during up to 38 years of follow-up.Methods:In a nationwide cohort study of 2,213,822 singletons born in Denmark during 1978–2015, we used cox regression to estimate the hazard ratio (HR) of mental disorders with a 95% CI.Results:A total of 3,00,679 (13.6%) individuals were diagnosed with mental disorders. The associations between suboptimal Apgar score 7–9 and mental disorders differed by attained age. In childhood (≤ 18 years), declining Apgar scores were associated with increased risks of overall mental disorders with HRs (95% CI) of 1.13(1.11-1.15), 1.34 (1.27–1.41), and 1.48 (1.31–1.67) for Apgar scores of 7–9, 4–6, and 1–3, respectively, compared with a score of 10. A dose-response association was seen even within the score range from 9 to 7 (HR 1.11 [95% CI: 1.08–1.13], 1.14 [1.10–1.18], and 1.20 [1.14–1.27], respectively). Of note, individuals with scores of 7–9 had increased risks of organic disorders (HR: 1.27, 95% CI: 1.05–1.53), neurotic disorders (HR: 1.07, 95% CI: 1.03–1.11), and a wide range of neurodevelopmental disorders, such as intellectual disability (1.87, 1.76–1.98), childhood autism (1.13, 1.05–1.22) and attention deficit hyperactivity disorder (1.10, 1.06–1.15). In early adulthood (19–39 years), suboptimal Apgar scores 7–9 were not associated with the risks of overall and specific mental disorders.Conclusion:Infants born with clinically reassuring but suboptimal 5-min scores 7–9 are at increased risks of a wide spectrum of mental disorders in childhood.
The Role of miRNAs as New Molecular Biomarkers for Dating the Age of Wound Production: A Systematic Review
Authors: De Simone Stefania , Giacani Elena , Bosco Maria Antonella , Vittorio Simona , Ferrara Michela , Bertozzi Giuseppe , Cipolloni Luigi , La Russa Raffaele 
Published: January 2022

Background:The timing of wounds production is a significant issue in forensic pathology. Although various methods have been evaluated, obtaining an accurate dating of lesions is still a challenge. The pathologist uses many parameters to value wound age, such as histological and immunohistochemical. In recent years, there have been many studies regarding the use of miRNAs in wound-age estimation; indeed, miRNAs have multiple potential uses in forensic pathology.Scope:This review aims to verify the efficacy and feasibility of miRNAs as a tool for determining the timing of lesions.Materials and Methods:The authors conducted the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed was used as a search engine to find articles published between January, 1st 2016 and October, 1st 2021, to evaluate the current state of the art regarding wound-age estimation.Results:A total of 256 articles were collected; after screening according to PRISMA guidelines, the systematic review included 8 articles. The studies included in this review were all Original articles evaluating the use of biomarkers for wound-age determination.Discussion and Conclusion:The literature review showed that analysis of miRNA is an innovative field of study with significant potentiality in forensic pathology. There are few studies, and almost all of them are at an early stage. The challenge is to understand how to standardize the samples' selection to obtain reliable experimental data. This observation represents a necessary prerequisite to planning further clinical trials.
The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4+ T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy
Authors: Honorato Layla , Witkin Steven S. , Mendes-Correa Maria Cássia , Conde Toscano Ana Luiza Castro , Linhares Iara Moreno , de Paula Anderson Vicente , Paião Heuder Gustavo Oliveira , de Paula Vanessa Salete , Lopes Amanda de Oliveira , Lima Silvia Helena , Raymundi Vanessa de Cássia , Ferreira Noely Evangelista , da Silva Junior Almir Ribeiro , Abrahim Karim Yaqub , Braz-Silva Paulo Henrique , Tozetto-Mendoza Tania Regina 
Published: January 2022

IntroductionTorque teno virus (TTV) is a non-pathogenic virus present in body fluids. Its titer in the circulation increases in association with immune suppression, such as in HIV-infected individuals. We evaluated if the TTV titer in saliva from HIV-positive individuals undergoing antiretroviral therapy (ART) was related to the circulating CD4+ T lymphocyte concentration and the HIV titer.MethodsSaliva was collected from 276 asymptomatic individuals undergoing ART, and an additional 48 individuals positive for AIDS-associated Kaposi's Sarcoma (AIDS-KS). The salivary TTV titer was measured by gene amplification analysis. The circulating CD4+ T lymphocyte and HIV levels were obtained by chart review.ResultsTTV was detectable in saliva from 80% of the asymptomatic subjects and 87% of those with AIDS-KS. In the asymptomatic group the median log10 TTV titer/ml was 3.3 in 200 males vs. 2.4 in 76 females (p &lt; 0.0001). TTV titer/ml was 3.7 when HIV was acquired by intravenous drug usage, 3.2 when by sexual acquisition and 2.4 when blood transfusion acquired. The salivary TTV titer was inversely correlated with the circulating CD4+ T lymphocyte level (p &lt; 0.0001) and positively correlated with the circulating HIV concentration (p = 0.0005). The median salivary TTV titer and circulating HIV titer were higher, and the CD4+ count was lower, in individuals positive for AIDS-KS than in the asymptomatic subjects (p &lt; 0.0001).ConclusionThe TTV titer in saliva is a potential biomarker for monitoring immune status in individuals undergoing ART.
From Acid Activation Mechanisms of Proton Conduction to Design of Inhibitors of the M2 Proton Channel of Influenza A Virus
Authors: Aledavood Elnaz , Selmi Beatrice , Estarellas Carolina , Masetti Matteo , Luque F. Javier 
Published: January 2022

With an estimated 1 billion people affected across the globe, influenza is one of the most serious health concerns worldwide. Therapeutic treatments have encompassed a number of key functional viral proteins, mainly focused on the M2 proton channel and neuraminidase. This review highlights the efforts spent in targeting the M2 proton channel, which mediates the proton transport toward the interior of the viral particle as a preliminary step leading to the release of the fusion peptide in hemagglutinin and the fusion of the viral and endosomal membranes. Besides the structural and mechanistic aspects of the M2 proton channel, attention is paid to the challenges posed by the development of efficient small molecule inhibitors and the evolution toward novel ligands and scaffolds motivated by the emergence of resistant strains.
Dynamic Changes of Endogenic or Exogenic β-Carboline Alkaloid Harmine in Different Mammals and Human in vivo at Developmental and Physiological States
Authors: Cao Ning , Li Shuping , Xu Aimin , Li Manlin , Zou Xiaoguang , Ke Zunji , Deng Gang , Cheng Xuemei , Wang Changhong 
Published: January 2022

ObjectiveSeveral β-carboline alkaloids (βCBs), such as harmine, harmaline, harmane, and nor-harmane, are effective for Alzheimer’s disease mouse models. They can be found in some plants, common foodstuffs, and blank plasma of various mammals. However, whether these compounds in mammals are exogenous or endogenous remain unclear.MethodsThe exposure levels of βCBs and of neurotransmitters in plasma and tissues of pup rats, aging rats, mice of different physiological states, and healthy volunteers were detected by using UPLC-MS/MS. Plasma and tissue samples from 110 newborn rats up to 29 days old at 11 sampling points were collected and were analyzed to determine the concentration variation of βCBs in the developmental phase of newborn rats. The plasma of rats aged 2 to 18 months was used to detect the variation trend of βCBs and with some neurotransmitters. The plasma samples of normal C57BL/6 mice, APP/PS1 double transgenic mice, and scopolamine-induced memory impairment mice were collected and were analyzed to compare the difference of βCBs in different physiological states. The exposure levels of βCBs such as harmine, harmaline, and harmane in plasma of 550 healthy volunteers were also detected and analyzed on the basis of gender, race, and age.ResultsResults showed that harmine was the main compound found in rats, mice, and human, which can be detected in a newborn rat plasma (0.16 ± 0.03 ng/ml) and brain (0.33 ± 0.14 ng/g) without any exogenous consumption. The concentration of harmine in rat plasma showed a decreasing trend similar to the exposure levels of neurotransmitters such as 5-hydroxytryptamine, acetylcholine chloride, glutamic acid, tyrosine, and phenylalanine during the growth period of 18 months. The harmine exposure in rats and human indicates high dependence on the physiological and pathological status such as aging, gender, and race.ConclusionThe dynamic changes of harmine exposure in different animals and human, in vivo, at developmental and physiological states indicate that harmine is a naturally and widely distributed endogenous substance in different mammals and human. In addition to exogenous ingestion, spontaneous synthesis might be another important source of harmine in mammals, which should be verified by further experiment.
Large Vessel Occlusion in Patients With Minor Ischemic Stroke in a Population-Based Study. The Dijon Stroke Registry
Authors: Duloquin Gauthier , Crespy Valentin , Jakubina Pauline , Giroud Maurice , Vergely Catherine , Béjot Yannick 
Published: January 2022

Introduction:Strategy for the acute management of minor ischemic stroke (IS) with large vessel occlusion (LVO) is under debate, especially the benefits of mechanical thrombectomy. The frequency of minor IS with LVO among overall patients is not well established. This study aimed to assess the proportion of minor IS and to depict characteristics of patients according to the presence of LVO in a comprehensive population-based setting.Methods:Patients with acute IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013–2017). All arterial imaging exams were reviewed to assess arterial occlusion. Minor stroke was defined as that with a National Institutes of Health Stroke Scale (NIHSS) score of &lt;6. Proportion of patients with LVO was estimated in the minor IS population. The clinical presentation of patients was compared according to the presence of an LVO.Results:Nine hundred seventy-one patients were registered, including 582 (59.9%) patients with a minor IS. Of these patients, 23 (4.0%) had a LVO. Patients with minor IS and LVO had more severe presentation [median 3 (IQR 2–5) vs. 2 (IQR 1–3), p = 0.001] with decreased consciousness (13.0 vs. 1.6%, p&lt;0.001) and cortical signs (56.5 vs. 30.8%, p = 0.009), especially aphasia (34.8 vs. 15.4%, p = 0.013) and altered item level of consciousness (LOC) questions (26.1 vs. 11.6%, p = 0.037). In multivariable analyses, only NIHSS score (OR = 1.45 per point; 95% CI: 1.11–1.91, p = 0.007) was associated with proximal LVO in patients with minor IS.Conclusion:Large vessel occlusion (LVO) in minor stroke is non-exceptional, and our findings highlight the need for emergency arterial imaging in any patients suspected of acute stroke, including those with minor symptoms because of the absence of obvious predictors of proximal LVO.
Association Between the EAT-Lancet Diet Pattern and Risk of Type 2 Diabetes: A Prospective Cohort Study
Authors: Xu Chenjie , Cao Zhi , Yang Hongxi , Hou Yabing , Wang Xiaohe , Wang Yaogang 
Published: January 2022

Background:The EAT-Lancet Commission has promulgated a sustainable dietary guideline and recommended that it was designed to improve the human health and support environmental sustainability.Objective:This research was designed to explore the association between this healthy diet pattern (EAT-Lancet diet pattern, EAT-LDP) and risk of type 2 diabetes (T2D).Methods:Between 2006 and 2010, a total of 59,849 participants from the UK Biobank without diabetes, cardiovascular disease, or cancers were included at baseline. The EAT-LDP score was constructed on the sum of 14 food components and then categorized into three tertiles. Multivariable Cox proportional hazards regression models were conducted to explore the association between EAT-LDP score and the risk of incident T2D. A mediation analysis was also implemented to disentangle the role of body mass index (BMI) and waist circumference in the relationship between EAT-LDP score and T2D.Results:During a median follow-up of 10 years, 2,461 incident T2D cases were recorded. In analyses that compared tertile 3 of the EAT-LDP score (highest) with tertile 1 (lowest), the hazard ratio (HR) for T2D was 0.81 (95% CI: 0.72–0.90) after adjusting for sociodemographic status and health-related factors. Participants who reported a one-point increase in the diet score were associated with a 6% decrease in risk of T2D (HR: 0.94, 95% CI: 0.91–0.97). A significant indirect association was observed between the EAT-LDP score and T2D (β: 0.66, 95% CI: 0.65–0.67), indicating that 44% of the association of EAT-LDP score with T2D was mediated by BMI. Additionally, 40% of the association of EAT-LDP score with T2D was mediated by waist circumference was also observed.Conclusions:Our findings indicate that a higher adherence to EAT-LDP contributes to lower risk of T2D. Further independent validation is needed to be conducted before applying the EAT-LDP to inform dietary guidelines.
Prophylactic Central Neck Dissection for cN1b Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis
Authors: Yan Xing-qiang , Zhang Zhen-zhen , Yu Wen-jie , Ma Zhao-sheng , Chen Min-long , Xie Bo-jian 
Published: January 2022

BackgroundThe value of prophylactic central neck dissection (PCND) for papillary thyroid carcinoma (PTC) with clinically evident lateral cervical lymph node metastases (cN1b) remains unclear. Therefore, a systematic review and meta-analysis was conducted to assess the efficacy and safety of PCND.MethodsA comprehensive systematic search was conducted on PubMed, Web of Science, Cochrane library and Embase databases up to September 2021 to identify eligible studies. Controlled clinical trials assessing therapeutic effects and safety of PCND for cN1b PTC patients were included. The risk of bias for each cohort study was assessed using the Newcastle-Ottawa Scale (NOS). The primary outcomes were indexes related to the locoregional recurrence (LRR) and surgical complications. Review Manager software V5.4.0 was used for statistical analysis. A fixed effects model was adopted for the data without heterogeneity, otherwise a random effects model was used.ResultsWe included 4 retrospective cohort studies, which comprised 483 PTC patients. There was no statistically significant difference in the central neck recurrence (CNR) (10.2% vs. 3.8%, relative risk (RR) = 1.82; 95%CI 0.90–3.67; P = 0.09), lateral neck recurrence (LNR) (5.1% vs. 7.7%, RR = 0.47; 95% CI 0.13–1.74; P = 0.26), and overall recurrence (OR) (18.9% vs. 16.9%, RR = 0.77; 95%CI 0.34–1.76; P = 0.54), between LND + PCND group and LND group. Simultaneously, PCND increased the risk of permanent hypoparathyroidism (11.4% vs. 4.5%, RR = 2.70, 95%CI 1.05–6.94; P = 0.04) and overall complications (17.0% vs. 5.3%, RR = 3.28; 95%CI 1.37–7.86; P = 0.008).ConclusionsThis meta-analysis showed that PCND did not have any advantage in preventing LRR for cN1b PTC. Meanwhile, PCND may result in the increased rate of surgical complications. However, the current evidence is limited and more clinical trials are still needed to further clarify the true role of PCND.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42021281825.
Free-Living User Perspectives on Musculoskeletal Pain and Patient-Reported Mobility With Passive and Powered Prosthetic Ankle-Foot Components: A Pragmatic, Exploratory Cross-Sectional Study
Authors: Kannenberg Andreas , Morris Arri R. , Hibler Karl D. 
Published: January 2022

IntroductionStudies with a powered prosthetic ankle-foot (PwrAF) found a reduction in sound knee loading compared to passive feet. Therefore, the aim of the present study was to determine whether anecdotal reports on reduced musculoskeletal pain and improved patient-reported mobility were isolated occurrences or reflect a common experience in PwrAF users.MethodsTwo hundred and fifty individuals with transtibial amputation (TTA) who had been fitted a PwrAF in the past were invited to an online survey on average sound knee, amputated side knee, and low-back pain assessed with numerical pain rating scales (NPRS), the PROMIS Pain Interference scale, and the PLUS-M for patient-reported mobility in the free-living environment. Subjects rated their current foot and recalled the ratings for their previous foot. Recalled scores were adjusted for recall bias by clinically meaningful amounts following published recommendations. Statistical comparisons were performed using Wilcoxon's signed rank test.ResultsForty-six subjects, all male, with unilateral TTA provided data suitable for analysis. Eighteen individuals (39%) were current PwrAF users, whereas 28 subjects (61%) had reverted to a passive foot. After adjustment for recall bias, current PwrAF users reported significantly less sound knee pain than they recalled for use of a passive foot (−0.5 NPRS, p = 0.036). Current PwrAF users who recalled sound knee pain ≥4 NPRS with a passive foot reported significant and clinically meaningful improvements in sound knee pain (−2.5 NPRS, p = 0.038) and amputated side knee pain (−3 NPRS, p = 0.042). Current PwrAF users also reported significant and clinically meaningful improvements in patient-reported mobility (+4.6 points PLUS-M, p = 0.016). Individuals who had abandoned the PwrAF did not recall any differences between the feet.DiscussionCurrent PwrAF users reported significant and clinically meaningful improvements in patient-reported prosthetic mobility as well as sound knee and amputated side knee pain compared to recalled mobility and pain with passive feet used previously. However, a substantial proportion of individuals who had been fitted such a foot in the past did not recall improvements and had reverted to passive feet. The identification of individuals with unilateral TTA who are likely to benefit from a PwrAF remains a clinical challenge and requires further research.