bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 and Alzheimer’s disease: how one crisis worsens the other
Authors: Xia Xiaohuan , Wang Yi , Zheng Jialin 
Published: May 2021

AbstractAlzheimer’s disease (AD) has emerged as a key comorbidity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The morbidity and mortality of COVID-19 are elevated in AD due to multiple pathological changes in AD patients such as the excessive expression of viral receptor angiotensin converting enzyme 2 and pro-inflammatory molecules, various AD complications including diabetes, lifestyle alterations in AD, and drug-drug interactions. Meanwhile, COVID-19 has also been reported to cause various neurologic symptoms including cognitive impairment that may ultimately result in AD, probably through the invasion of SARS-CoV-2 into the central nervous system, COVID-19-induced inflammation, long-term hospitalization and delirium, and post-COVID-19 syndrome. In addition, the COVID-19 crisis also worsens behavioral symptoms in uninfected AD patients and poses new challenges for AD prevention. In this review, we first introduce the symptoms and pathogenesis of COVID-19 and AD. Next, we provide a comprehensive discussion on the aggravating effects of AD on COVID-19 and the underlying mechanisms from molecular to social levels. We also highlight the influence of COVID-19 on cognitive function, and propose possible routes of viral invasion into the brain and potential mechanisms underlying the COVID-19-induced cognitive impairment. Last, we summarize the negative impacts of COVID-19 pandemic on uninfected AD patients and dementia prevention.
Comprehensive analysis of coding and non-coding RNA transcriptomes related to hypoxic adaptation in Tibetan chickens
Authors: Zhang Ying , Su Woyu , Zhang Bo , Ling Yao , Kim Woo Kyun , Zhang Hao 
Published: May 2021

Abstract
Background
Tibetan chickens, a unique native breed in the Qinghai-Tibet Plateau of China, possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment. Increasing evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play roles in the hypoxic adaptation of high-altitude animals, although their exact involvement remains unclear.

Results
This study aimed to elucidate the global landscape of mRNAs, lncRNAs, and miRNAs using transcriptome sequencing to construct a regulatory network of competing endogenous RNAs (ceRNAs) and thus provide insights into the hypoxic adaptation of Tibetan chicken embryos. In total, 354 differentially expressed genes (DE genes), 389 differentially expressed lncRNAs (DE lncRNAs), and 73 differentially expressed miRNAs (DE miRNAs) were identified between Tibetan chickens (TC) and control Chahua chickens (CH). GO and KEGG enrichment analysis revealed that several important DE miRNAs and their target DE lncRNAs and DE genes are involved in angiogenesis (including blood vessel development and blood circulation) and energy metabolism (including glucose, carbohydrate, and lipid metabolism). The ceRNA network was then constructed with the predicted DE gene-DE miRNA-DE lncRNA interactions, which further revealed the regulatory roles of these differentially expressed RNAs during hypoxic adaptation of Tibetan chickens.

Conclusions
Analysis of transcriptomic data revealed several key candidate ceRNAs that may play high-priority roles in the hypoxic adaptation of Tibetan chickens by regulating angiogenesis and energy metabolism. These results provide insights into the molecular mechanisms of hypoxic adaptation regulatory networks from the perspective of coding and non-coding RNAs.
Impact of modification to DSM-5 criterion A for hypomania/mania in newly diagnosed bipolar patients: findings from the prospective BIO study
Authors: Fredskild Mette U. , Stanislaus Sharleny , Coello Klara , Melbye Sigurd A. , Kjærstad Hanne Lie , Sletved Kimie Stefanie Ormstrup , Suppes Trisha , Vinberg Maj , Kessing Lars Vedel 
Published: May 2021

Abstract
Background
DSM-IV states that criterion A for diagnosing hypomania/mania is mood change. The revised DSM-5 now states that increased energy or activity must be present alongside mood changes to diagnose hypomania/mania, thus raising energy/activity to criterion A. We set out to investigate how the change in criterion A affects the diagnosis of hypomanic/manic visits in patients with a newly diagnosed bipolar disorder.

Results
In this prospective cohort study, 373 patients were included (median age = 32; IQR, 27–40). Women constituted 66% (n = 245) of the cohort and 68% of the cohort (n = 253) met criteria for bipolar type II, the remaining patients were diagnosed bipolar type I. Median number of contributed visits was 2 per subject (IQR, 1–3) and median follow-up time was 3 years (IQR, 2–4). During follow-up, 127 patients had at least one visit with fulfilled DSM-IV criterion A. Applying DSM-5 criterion A reduced the number of patients experiencing a hypomanic/manic visit by 62% at baseline and by 50% during longitudinal follow-up, compared with DSM-IV criterion A. Fulfilling DSM-5 criterion A during follow-up was associated with higher modified young mania rating scale score (OR = 1.51, CL [1.34, 1.71], p < 0.0001) and increased number of visits contributed (OR = 1.86, CL [1.52, 2.29], p < 0.0001).

Conclusion
Applying the stricter DSM-5 criterion A in a cohort of newly diagnosed bipolar patients reduced the number of patients experiencing a hypomanic/manic visit substantially, and was associated with higher overall young mania rating scale scores, compared with DSM-IV criterion A. Consequently, fewer hypomanic/manic visits may be detected in newly diagnosed bipolar patients with applied DSM-5 criterion A, and the upcoming ICD-11, which may possibly result in longer diagnostic delay of BD as compared with the DSM-IV.
The effective interplay of (non-) selective NSAIDs with neostigmine in animal models of analgesia and inflammation
Authors: Gowayed Mennatallah A , Abdel-Bary Amany , El-Tahan Rasha A 
Published: May 2021

Abstract
Background
Surgical procedures cause perioperative immunosuppression and neuroendocrine stress, exerted by activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. The acetylcholinesterase inhibitor (ACHEI); neostigmine, is known clinically for its analgesic effect in the perioperative phases proving high efficacy; besides possessing anti-inflammatory properties controlling immune cells and cytokine level. Hence, this study evaluated and compared the analgesic and anti-inflammatory activities of the combination of selective Cox-2 inhibitor; celecoxib, with neostigmine versus a combination of the non-selective Cox inhibitor; diclofenac, with neostigmine; in different experimental models of analgesia and inflammation in rats.

Methods
Analgesic activity of neostigmine with/without diclofenac or celecoxib was assessed in female Sprague-Dawely rats using the tail clip model and acetic acid induced writhing. Serum level of β-endorphin was assessed after the tail clip test. The anti-inflammatory activity was evaluated using acute and sub-chronic formalin induced paw edema. At the end of the sub-chronic formalin test, blood samples were collected for analysis of anti-inflammatory, liver and kidney function markers. Livers, kidneys and hind paws were also examined histopathologically.

Results
Addition of neostigmine to selective or non-selective NSAIDs (celecoxib or diclofenac) causes an increased level of analgesia of NSAIDs with rapid onset of action and short duration, while causing potentiation of the anti-inflammatory effect of neostigmine as seen in the tail clip, writhing, formalin test, Cox-1 and Cox-2 activities, serum β-endorphin, TNF-α, NF-кB and HS-CRP. All combinations of this study disturb some kidney and liver functions, however with normal histopathological appearances, while hind paws reveal improved inflammatory infiltration in all treated groups.

Conclusions
Selective and non-selective NSAIDs examined in this study could be good adjunct options to general anesthetic agents and neostigmine in perioperative stages, an outcome that needs further clinical investigations.
Therapeutic targeting of Lyn kinase to treat chorea-acanthocytosis
Authors: Peikert Kevin , Federti Enrica , Matte Alessandro , Constantin Gabriela , Pietronigro Enrica Caterina , Fabene Paolo Francesco , Defilippi Paola , Turco Emilia , Del Gallo Federico , Pucci Pietro , Amoresano Angela , Illiano Anna , Cozzolino Flora , Monti Maria , Garello Francesca , Terreno Enzo , Alper Seth Leo , Glaß Hannes , Pelzl Lisann , Akgün Katja , Ziemssen Tjalf , Ordemann Rainer , Lang Florian , Brunati Anna Maria , Tibaldi Elena , Andolfo Immacolata , Iolascon Achille , Bertini Giuseppe , Buffelli Mario , Zancanaro Carlo , Lorenzetto Erika , Siciliano Angela , Bonifacio Massimiliano , Danek Adrian , Walker Ruth Helen , Hermann Andreas , De Franceschi Lucia 
Published: May 2021

AbstractChorea-Acanthocytosis (ChAc) is a devastating, little understood, and currently untreatable neurodegenerative disease caused by VPS13A mutations. Based on our recent demonstration that accumulation of activated Lyn tyrosine kinase is a key pathophysiological event in human ChAc cells, we took advantage of Vps13a−/− mice, which phenocopied human ChAc. Using proteomic approach, we found accumulation of active Lyn, γ-synuclein and phospho-tau proteins in Vps13a−/− basal ganglia secondary to impaired autophagy leading to neuroinflammation. Mice double knockout Vps13a−/− Lyn−/− showed normalization of red cell morphology and improvement of autophagy in basal ganglia. We then in vivo tested pharmacologic inhibitors of Lyn: dasatinib and nilotinib. Dasatinib failed to cross the mouse brain blood barrier (BBB), but the more specific Lyn kinase inhibitor nilotinib, crosses the BBB. Nilotinib ameliorates both Vps13a−/− hematological and neurological phenotypes, improving autophagy and preventing neuroinflammation. Our data support the proposal to repurpose nilotinib as new therapeutic option for ChAc patients.
Green synthesized plant-based silver nanoparticles: therapeutic prospective for anticancer and antiviral activity
Authors: Jain Nancy , Jain Priyanshu , Rajput Devyani , Patil Umesh Kumar 
Published: May 2021

AbstractNanotechnology holds an emerging domain of medical science as it can be utilized virtually in all areas. Phyto-constituents are valuable and encouraging candidates for synthesizing green silver nanoparticles (AgNPs) which possess great potentials toward chronic diseases. This review gives an overview of the Green approach of AgNPs synthesis and its characterization. The present review further explores the potentials of Phyto-based AgNPs toward anticancer and antiviral activity including its probable mechanism of action. Green synthesized AgNPs prepared by numerous medicinal plants extract are critically reviewed for cancer and viral infection. Thus, this article mainly highlights green synthesized Phyto-based AgNPs with their potential applications for cancer and viral infection including mechanism of action and therapeutic future prospective in a single window.
Mössbauer study of iron gall inks on historical documents
Authors: Lerf A. , Wagner F. E. , Dreher M. , Espejo T. , Pérez-Rodríguez J.-L. 
Published: May 2021

Abstract
Iron gall ink was used in the Western world as a permanent writing material already in late Roman times and throughout the Middle Ages, until it became obsolete in the twentieth century. There is much interest in experimental methods to determine the state of the ink and its degradation products on historical documents. Mössbauer spectroscopy with 57Fe is such a method, and it has the particular advantage to be sensitive to the chemical bonding of iron, but this method has only rarely been applied to historical documents. In this paper we present Mössbauer data for two damaged documents from a Library in Granada and a handwritten German book from the eighteenth century. In addition to the inked parts of the manuscripts, ink-free parts were studied to determine the amount and chemical state of the iron in the papers. These new results are discussed in the context of previously published Mössbauer data. In one of the investigated documents Fe(II)-oxalate, FeC2O4·2H2O, was observed. The assignment of the various Fe3+ sites in the different documents is rather difficult and often there is a superposition of various species. Known forms of iron gallate are definitely not present on the inked papers. The observed ferric species can be remains of Fe3+ polyphenol complexes of the ink, complexes of Fe3+ with degradation products of the cellulose of the paper or gum arabic, or very small iron oxide or hydroxide nanoparticles.
Adequacy of alcohol-based handrub solution production practice in response to COVID-19 in public hospitals found in Addis Ababa, Ethiopia: a multicentered cross-sectional study
Authors: Selam Muluken Nigatu , Bayisa Regasa , Ababu Andualem , Abdella Mahdi , Diriba Edessa , Wale Minychel , Baye Assefa Mulu 
Published: May 2021

Abstract
Background
Proper hand hygiene using alcohol-based handrub (ABHR) is an effective preventive approach for the current Coronavirus Disease 2019 (COVID-19) pandemic and other infections. World Health Organization recommends local production of ABHR solution in healthcare settings which provides a feasible alternative to the use of relatively expensive commercially produced hand sanitizers. The aim of this study was to explore the adequacy of ABHR solution production practice in response to COVID-19 in public hospitals of Addis Ababa, Ethiopia.

Methods
A cross-sectional observational study was applied using assessment checklist for evaluation of the adequacy of ABHR production practice in compounding units of public hospitals. The evaluation was done with regard to the standard requirements as per the checklist. Statistical Package for Social Sciences (SPSS) version 23 was used for data entry and analysis. Descriptive statistics was employed for analyses of data and categorical variables were described by frequencies and percentages.

Results
Out of the 13 public hospitals observed in the study, 11 facilities had dedicated premises for compounding of ABHR solution. Seven facilities determined the concentration of ethanol in ABHR solution using alcoholmeters. Only one health facility had a titration kit and performed a strength test for the hydrogen peroxide raw material. Thermal and chemical disinfection processes were practiced for cleaning of recycled dispensing bottles only in 3 and 2 hospitals, respectively. Most of the hospitals (11 facilities) had standard operating procedures (SOPs) for production, but the majority lack SOPs for beyond-use-date assignment (11 facilities), premise and equipment cleaning (12 facilities), and disinfection of recycled bottles (12 facilities).

Conclusion
Most hospitals have fulfilled the majority requirements of premises required for compounding of ABHR solution in their facilities. Five hospitals did not verify the concentration of ethanol in the ABHR solution which might affect the effectiveness of the product. Generally, lower compliance of the majority studied hospitals to good compounding practice was observed during ABHR solution production especially for product preparation, quality control, and documentation.
Interleukin-9 promotes intestinal barrier injury of sepsis: a translational research
Authors: Sun Jia-Kui , Zhou Jing , Sun Xin-Pei , Shen Xiao , Zhu Dong-Mei , Wang Xiang , Zhou Su-Ming , Mu Xin-Wei 
Published: May 2021

Abstract
Background
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Intestinal mucosal barrier injury is one of the important manifestations of sepsis. Interleukin-9 (IL-9) and IL-9-producing CD4(+) T cells were emerging pro-inflammatory mediators with development of intestinal injury. However, it is unclear whether IL-9 is related to the intestinal barrier injury of sepsis.

Methods
To investigate the roles of IL-9-producing CD4(+) T cells and IL-9 in the process of barrier injury in sepsis, serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels were measured in septic patients and controls. The markers of barrier function in serum and intestinal tissue were also collected in septic rats. Moreover, the barrier injury degree and survival rate of septic rats were also investigated after increasing or interfering with IL-9 expression.

Results
The serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels were significantly higher in septic patients or rats than those in controls. IL-9-producing CD4(+) T cells and IL-9 levels were positively correlated with D-lactate levels and had a high predictive value of 28-day mortality in septic patients. The non-survivors had significantly higher serum T cell percentages, IL-9, and D-lactate levels compared with survivors. In septic rats, IL-9 increased the expression levels of D-lactate, whereas that decreased the expression levels of zonula occludens 1. Moreover, the barrier injury was aggravated or alleviated by increasing or interfering with IL-9 expression, respectively. Survival rate analysis also showed that IL-9 decreased the 14-day survival rate of septic rats.

Conclusion
IL-9 is closely related to intestinal mucosal barrier injury and mortality in sepsis. IL-9 blockade has the potential to improve the barrier injury in sepsis.

Trial registration
The study was registered at ClinicalTrials.gov (ID: NCT03791866, Date: December 2018).
Functional relationship between photosynthetic leaf gas exchange in response to silicon application and water stress mitigation in sugarcane
Authors: Verma Krishan K. , Song Xiu-Peng , Verma Chhedi Lal , Chen Zhong-Liang , Rajput Vishnu D. , Wu Kai-Chao , Liao Fen , Chen Gan-Lin , Li Yang-Rui 
Published: May 2021

Abstract
Background
Water stress is one of the serious abiotic stresses that negatively influences the growth, development and production of sugarcane in arid and semi-arid regions. However, silicon (Si) has been applied as an alleviation strategy subjected to environmental stresses.

Methods
In this experiment, Si was applied as soil irrigation in sugarcane plants to understand the mitigation effect of Si against harmful impact of water stress on photosynthetic leaf gas exchange.

Results
In the present study we primarily revealed the consequences of low soil moisture content, which affect overall plant performance of sugarcane significantly. Silicon application reduced the adverse effects of water stress by improving the net photosynthetic assimilation rate (Anet) 1.35–18.75%, stomatal conductance to water vapour (gs) 3.26–21.57% and rate of transpiration (E) 1.16–17.83%. The mathematical models developed from the proposed hypothesis explained the functional relationships between photosynthetic responses of Si application and water stress mitigation.

Conclusions
Silicon application showed high ameliorative effects on photosynthetic responses of sugarcane to water stress and could be used for mitigating environmental stresses in other crops, too, in future.
Long term results of accelerated 9 mW corneal crosslinking for early progressive keratoconus: the Siena Eye-Cross Study 2
Authors: Mazzotta Cosimo , Raiskup Frederik , Hafezi Farhad , Torres-Netto Emilio A , Armia Balamoun Ashraf , Giannaccare Giuseppe , Bagaglia Simone Alex 
Published: May 2021

Abstract
Purpose
To assess clinical results of the 9 mW/5.4 J/cm2 accelerated crosslinking (ACXL) in the treatment of progressive keratoconus (KC) over a span of 5 years.

Methods
The prospective open non-randomized interventional study (Siena Eye-Cross Study 2) included 156 eyes of 112 patients with early progressive KC undergoing the Epi-Off 9 mW/5.4 J/cm2 ACXL at the Siena Crosslinking Centre, Italy. The mean age was 18.05 ± 5.6 years. The 20-min treatments were performed using the New KXL I (Avedro, Waltham, USA), 10 min of 0.1% HPMC Riboflavin soaking (VibeX Rapid, Avedro, Waltham, USA) and 10 min of continuous-light UV-A irradiation. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), Kmax, coma, minimum corneal thickness (MCT), surface asymmetry index (SAI), endothelial cell count (ECC) were measured, and corneal OCT performed.

Results
UDVA and CDVA improved significantly at the 3rd (P = 0.028), Δ + 0.17 Snellen lines and 6th postoperative month, respectively (P < 0.001), Δ + 0.23 Snellen lines. Kmax improved at the 6th postoperative month (P = 0.03), Δ − 1.49 diopters from the baseline value. Also, coma aberration value improved significantly (P = 0.004). A mild temporary haze was recorded in 14.77% of patients without affecting visual acuity and without persistent complications. Corneal OCT revealed a mean demarcation line depth at 332.6 ± 33.6 μm.

Conclusion
The 5-year results of Epi-Off 9 mW/5.4 J/cm2 ACXL demonstrated statistically significant improvements in UCVA and CDVA, corneal curvature and corneal higher-order aberrations which confers a long-term stability for progressive ectasia. Based on the results of the Siena Eye-Cross Study 2, the 9 mW/5.4 J/cm2 ACXL is a candidate to be the natural evolution of Epi-Off CXL treatment for the management of early progressive corneal ectasia, and thus optimize clinic workflow.
Glycine receptor antibodies and coeliac disease-related neurological dysfunction
Authors: Kass-Iliyya Lewis , Sarrigiannis Ptolemaios G. , Sanders David S. , Hadjivassiliou Marios 
Published: May 2021

AbstractGluten sensitivity can manifest with a spectrum of neurological dysfunction including ataxia, encephalopathy and neuropathy with or without associated coeliac disease (CD). Gluten sensitivity can also present with central nervous system (CNS) hyperexcitability and cortical myoclonus which is often accompanied with refractory CD. CNS hyperexcitability can also be associated with Glutamic Acid Decarboxylase (GAD) antibodies or much less commonly with Glycine Receptor Antibodies (GlyR-Abs) but the direct pathogenic roles of these antibodies remain debatable. We have previously reported a link between gluten sensitivity and anti-GAD associated ataxia which improves with the adoption of gluten-free diet. It is unclear if a similar link exists between gluten driven CNS hyperexcitability and the presence of GlyR-Abs. We report two cases of CD presenting with CNS hyperexcitability and associated GlyR-Abs. Apart from ataxia and cortical myoclonus, one patient had refractory CD and died from enteropathy-associated T-cell lymphoma. The other patient not only improved with strict gluten-free diet but also showed serological elimination of circulating GlyR-Abs. We conclude that there is an interaction between gluten sensitivity and GlyR-Abs-associated CNS hyperexcitability and in such patients gluten-free diet is an important therapeutic intervention. The elimination of GlyR-Abs by the adoption of gluten free diet suggests that these antibodies may represent an epiphenomenon rather than being directly implicated in the pathogenesis.