bluuebunny/crossref_metadata_2025_split huggingface dataset:
A large database study of hospitalization charges and follow-up re-admissions in US lumbar fusion surgeries using a cellular bone allograft (CBA) versus recombinant human bone morphogenetic protein-2 (rhBMP-2)
Authors: Wetzell Bradley , McLean Julie B. , Moore Mark A. , Kondragunta Venkateswarlu , Dorsch Kimberly 
Published: November 2020

Abstract
Background
The objective of this study was to retrospectively compare initial procedure and 12-month follow-up hospitalization charges and resource utilization (lengths of stay; LOS) for lumbar fusion surgeries using either recombinant human bone morphogenetic protein-2 (rhBMP-2) or a cellular bone allograft comprised of viable lineage-committed bone cells (V-CBA) via a large US healthcare system database. Potentially relevant re-admissions during the follow-up period were also assessed.

Methods
A total of 16,172 patients underwent lumbar fusion surgery using V-CBA or rhBMP-2, of whom 3503 (21.66%) patients had follow-up re-admission data. Initial patient, procedure, and hospital characteristics were assessed to determine confounding factors. Multivariate regression modeling compared differences in hospitalization charges (in 2018 US dollars) and LOS (in days) between the groups, as well as incidences of potentially relevant re-admissions during the 12-month follow-up period.

Results
The adjusted mean initial procedure and 12-month follow-up hospital charges were significantly lower in the V-CBA group versus the rhBMP-2 group ($109,061 and $108,315 versus $160,191 and $130,406, respectively; P < 0.0001 for both comparisons). This disparity remained in an ad hoc comparison of charges for initial single-level treatments only (V-CBA = $103,064, rhBMP-2 = $149,620; P < 0.0001). The adjusted mean initial LOS were significantly lower in the V-CBA group (3.77 days) versus the rhBMP-2 group (3.88 days; P < 0.0001), but significantly higher for the cumulative follow-up hospitalizations in the 12-month follow-up period (7.87 versus 7.46 days, respectively; P < 0.0001). Differences in rates of follow-up re-admissions aligned with comorbidities at the initial procedure. Subsequent lumbar fusion rates were comparable, but significantly lower for V-CBA patients who had undergone single-level treatments only, in spite of V-CBA patients having significantly higher rates of initial comorbidities that could negatively impact clinical outcomes.

Conclusions
The results of this study indicate that use of V-CBA for lumbar fusion surgeries performed in the US may result in substantially lower overall hospitalization charges versus rhBMP-2, with both exhibiting similar rates of 12-month re-admissions and subsequent lumbar fusion procedures.
Better outcomes and reduced failures for arthroplasty over osteotomy for advanced compartmental knee osteoarthritis in patients older than 50 years
Authors: Migliorini Filippo , Driessen Arne , Oliva Francesco , Maffulli Gayle D. , Tingart Markus , Maffulli Nicola 
Published: November 2020

AbstractBackgroundBoth compartmental knee arthroplasty (CKA) and open-wedge high tibial osteotomy (HTO) may be used to treat patients older than 50 years of age with advanced compartmental osteoarthritis (OA) secondary to leg axis deformities. A meta-analysis was conducted to clarify the role of open-wedge HTO versus CKA for patients older than 50 years with advanced compartmental knee OA. The present investigation aimed to analyse the clinical outcomes, implant failure and survivorship.MethodsThis meta-analysis was performed in accordance with the PRISMA guidelines. In September 2020, the main online databases were accessed. All clinical trials comparing the outcomes of open-wedge HTO versus CKA for compartmental knee OA were considered. Data analysis was performed through the Review Manager Software 5.3 (the Nordic Cochrane Collaboration, Copenhagen). Implant survivorship was analysed with a Kaplan-Meier (KM) curve that was performed using the STATA/MP software (StataCorp, College Station, TX).ResultsData from 618 (HTO, 307; CKA, 311) patients were collected. Good baseline comparability among patient age, BMI and gender was detected. The Tegner Activity Scale was higher in the CKA group (P= 0.04), as were the Lysholm score (P= 0.001), the International Knee Documentation Committee (P= 0.0001) and the Knee injury and Osteoarthritis Outcome Score (P= 0.05). At a mean follow-up of 5 years, revisions were less in the CKA cohort (OR, 2.27;P= 0.004). The Kaplan-Meier curve evidenced longer implant survivorship in favour of the CKA group (P= 0.01).ConclusionIn patients older than 50 years of age with compartmental knee OA secondary to frontal axis leg deformities, CKA performed better than open-wedge HTO.
An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases
Authors: Robert Jerome , Weilinger Nicholas L. , Cao Li-Ping , Cataldi Stefano , Button Emily B. , Stukas Sophie , Martin Emma M. , Seibler Philip , Gilmour Megan , Caffrey Tara M. , Rowe Elyn M. , Fan Jianjia , MacVicar Brian , Farrer Matthew J. , Wellington Cheryl L. 
Published: November 2020

Abstract
Introduction
The neurovascular unit (NVU) – the interaction between the neurons and the cerebrovasculature – is increasingly important to interrogate through human-based experimental models. Although advanced models of cerebral capillaries have been developed in the last decade, there is currently no in vitro 3-dimensional (3D) perfusible model of the human cortical arterial NVU.

Method
We used a tissue-engineering technique to develop a scaffold-directed, perfusible, 3D human NVU that is cultured in native-like flow conditions that mimics the anatomy and physiology of cortical penetrating arteries.

Results
This system, composed of primary human vascular cells (endothelial cells, smooth muscle cells and astrocytes) and induced pluripotent stem cell (iPSC) derived neurons, demonstrates a physiological multilayer organization of the involved cell types. It reproduces key characteristics of cortical neurons and astrocytes and enables formation of a selective and functional endothelial barrier. We provide proof-of-principle data showing that this in vitro human arterial NVU may be suitable to study neurovascular components of neurodegenerative diseases such as Alzheimer’s disease (AD), as endogenously produced phosphorylated tau and beta-amyloid accumulate in the model over time. Finally, neuronal and glial fluid biomarkers relevant to neurodegenerative diseases are measurable in our arterial NVU model.

Conclusion
This model is a suitable research tool to investigate arterial NVU functions in healthy and disease states. Further, the design of the platform allows culture under native-like flow conditions for extended periods of time and yields sufficient tissue and media for downstream immunohistochemistry and biochemistry analyses.
COVID-19 in humanitarian settings: documenting and sharing context-specific programmatic experiences
Authors: Singh Neha S. , Abrahim Orit , Altare Chiara , Blanchet Karl , Favas Caroline , Odlum Alex , Spiegel Paul B. 
Published: November 2020

AbstractHumanitarian organizations have developed innovative and context specific interventions in response to the COVID-19 pandemic as guidance has been normative in nature and most are not humanitarian specific. In April 2020, three universities developed a COVID-19 humanitarian-specific website (www.covid19humanitarian.com) to allow humanitarians from the field to upload their experiences or be interviewed by academics to share their creative responses adapted to their specific country challenges in a standardised manner. These field experiences are reviewed by the three universities together with various guidance documents and uploaded to the website using an operational framework. The website currently hosts 135 guidance documents developed by 65 different organizations, and 65 field experiences shared by 29 organizations from 27 countries covering 38 thematic areas. Examples of challenges and innovative solutions from humanitarian settings are provided for triage and sexual and gender-based violence. Offering open access resources on a neutral platform by academics can provide a space for constructive dialogue among humanitarians at the country, regional and global levels, allowing humanitarian actors at the country level to have a strong and central voice. We believe that this neutral and openly accessible platform can serve as an example for future large-scale emergencies and epidemics.
Evodiamine suppresses non-small cell lung cancer by elevating CD8+ T cells and downregulating the MUC1-C/PD-L1 axis
Authors: Jiang Ze-Bo , Huang Ju-Min , Xie Ya-Jia , Zhang Yi- Zhong , Chang Chan , Lai Huan-Ling , Wang Wenjun , Yao Xiao-Jun , Fan Xing-Xing , Wu Qi-Biao , Xie Chun , Wang Mei-Fang , Leung Elaine Lai-Han 
Published: November 2020

Abstract
Background
Accumulating evidence showed that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Programmed Death Ligand 1 (PD-L1) is expressed in many cancer cell types, while its binding partner Programmed Death 1 (PD1) is expressed in activated T cells and antigen-presenting cells. Whereas, its dysregulation in the microenvironment is poorly understood. In the present study, we confirmed that evodiamine downregulates MUC1-C, resulting in modulating PD-L1 expression in non-small cell lung cancer (NSCLC).

Methods
Cell viability was measured by MTT assays. Apoptosis, cell cycle and surface PD-L1 expression on NSCLC cells were analyzed by flow cytometry. The expression of MUC1-C and PD-L1 mRNA was measured by real time RT-PCR methods. Protein expression was examined in evodiamine-treated NSCLC cells using immunoblotting or immunofluorescence assays. The effects of evodiamine treatment on NSCLC sensitivity towards T cells were investigated using human peripheral blood mononuclear cells and Jurkat, apoptosis and IL-2 secretion assays. Female H1975 xenograft nude mice were used to assess the effect of evodiamine on tumorigenesis in vivo. Lewis lung carcinoma model was used to investigate the therapeutic effects of combination evodiamine and anti-PD-1 treatment.

Results
We showed that evodiamine significantly inhibited growth, induced apoptosis and cell cycle arrest at G2 phase of NSCLC cells. Evodiamine suppressed IFN-γ-induced PD-L1 expression in H1975 and H1650. MUC1-C mRNA and protein expression were decreased by evodiamine in NSCLC cells as well. Evodiamine could downregulate the PD-L1 expression and diminish the apoptosis of T cells. It inhibited MUC1-C expression and potentiated CD8+ T cell effector function. Meanwhile, evodiamine showed good anti-tumor activity in H1975 tumor xenograft, which reduced tumor size. Evodiamine exhibited anti-tumor activity by elevation of CD8+ T cells in vivo in Lewis lung carcinoma model. Combination evodiamine and anti-PD-1 mAb treatment enhanced tumor growth control and survival of mice.

Conclusions
Evodiamine can suppress NSCLC by elevating of CD8+ T cells and downregulating of the MUC1-C/PD-L1 axis. Our findings uncover a novel mechanism of action of evodiamine and indicate that evodiamine represents a potential targeted agent suitable to be combined with immunotherapeutic approaches to treat NSCLC cancer patients. MUC1-C overexpression is common in female, non-smoker, patients with advanced-stage adenocarcinoma.
Deep sequencing reveals a DAP1 regulatory haplotype that potentiates autoimmunity in systemic lupus erythematosus
Authors: Raj Prithvi , Song Ran , Zhu Honglin , Riediger Linley , Jun Dong-Jae , Liang Chaoying , Arana Carlos , Zhang Bo , Gao Yajing , Wakeland Benjamin E. , Dozmorov Igor , Zhou Jinchun , Kelly Jennifer A. , Lauwerys Bernard R. , Guthridge Joel M. , Olsen Nancy J. , Nath Swapan K. , Pasare Chandrashekhar , van Oers Nicolai , Gilkeson Gary , Tsao Betty P. , Gaffney Patrick M. , Gregersen Peter K. , James Judith A. , Zuo Xiaoxia , Karp David R. , Li Quan-Zhen , Wakeland Edward K. 
Published: November 2020

AbstractBackgroundSystemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease characterized by the development of anti-nuclear antibodies. Susceptibility to SLE is multifactorial, with a combination of genetic and environmental risk factors contributing to disease development. Like other polygenic diseases, a significant proportion of estimated SLE heritability is not accounted for by common disease alleles analyzed by SNP array-based GWASs. Death-associated protein 1 (DAP1) was implicated as a candidate gene in a previous familial linkage study of SLE and rheumatoid arthritis, but the association has not been explored further.ResultsWe perform deep sequencing across the DAP1 genomic segment in 2032 SLE patients, and healthy controls, and discover a low-frequency functional haplotype strongly associated with SLE risk in multiple ethnicities. We find multiple cis-eQTLs embedded in a risk haplotype that progressively downregulates DAP1 transcription in immune cells. Decreased DAP1 transcription results in reduced DAP1 protein in peripheral blood mononuclear cells, monocytes, and lymphoblastoid cell lines, leading to enhanced autophagic flux in immune cells expressing the DAP1 risk haplotype. Patients with DAP1 risk allele exhibit significantly higher autoantibody titers and altered expression of the immune system, autophagy, and apoptosis pathway transcripts, indicating that the DAP1 risk allele mediates enhanced autophagy, leading to the survival of autoreactive lymphocytes and increased autoantibody.ConclusionsWe demonstrate how targeted sequencing captures low-frequency functional risk alleles that are missed by SNP array-based studies. SLE patients with the DAP1 genotype have distinct autoantibody and transcription profiles, supporting the dissection of SLE heterogeneity by genetic analysis.
Parasitic diseases of equids in Iran (1931–2020): a literature review
Authors: Sazmand Alireza , Bahari Aliasghar , Papi Sareh , Otranto Domenico 
Published: November 2020

AbstractParasitic infections can cause many respiratory, digestive and other diseases and contribute to some performance conditions in equids. However, knowledge on the biodiversity of parasites of equids in Iran is still limited. The present review covers all the information about parasitic diseases of horses, donkeys, mules and wild asses in Iran published as articles in Iranian and international journals, dissertations and congress papers from 1931 to July 2020. Parasites so far described in Iranian equids include species of 9 genera of the Protozoa (Trypanosoma,Giardia,Eimeria,Klossiella,Cryptosporidium,Toxoplasma,Neospora,TheileriaandBabesia), 50 helminth species from the digestive system (i.e., 2 trematodes, 3 cestodes and 37 nematodes) and from other organs (i.e.,Schistosoma turkestanica,Echinococcus granulosus,Dictyocaulus arnfieldi,Parafilaria multipapillosa,Setaria equinaand 3Onchocercaspp.). Furthermore, 16 species of hard ticks, 3 mite species causing mange, 2 lice species, and larvae of 4Gastrophilusspecies andHippobosca equinahave been reported from equids in Iran. Archeoparasitological findings in coprolites of equids includeFasciola hepatica,Oxyuris equi,Anoplocephalaspp.and intestinal strongyles. Parasitic diseases are important issues in terms of animal welfare, economics and public health; however, parasites and parasitic diseases of equines have not received adequate attention compared with ruminants and camels in Iran. The present review highlights the knowledge gaps related to equines about the presence, species, genotypes and subtypes ofNeospora hughesi,Sarcocystisspp.,Trichinellaspp.,Cryptosporidiumspp.,Giardia duodenalis,Blastocystisand microsporidia. Identification of ticks vectoring pathogenic parasites, bacteria and viruses has received little attention, too. The efficacy of common horse wormers also needs to be evaluated systematically.Graphical Abstract
Effect on autonomic nervous activity of applying hot towels for 10 s to the back during bed baths
Authors: Shishido Inaho , Konya Issei , Yano Rika 
Published: November 2020

Abstract
Background
Bed baths are a daily nursing activity to maintain patients’ hygiene. Those may provide not only comfort but also relaxation. Notably, applying a hot towel to the skin for 10 s (AHT10s) during bed baths helped to reduce the risk of skin tears and provided comfort and warmth in previous studies. However, it is still unclear whether autonomic nervous system is affected by bed baths. Thus, this study investigated the effect on the autonomic nervous activity of applying hot towels for 10 s to the back during bed baths.

Methods
This crossover study had 50 participants (25 men and women each; average age 22.2 ± 1.6 years; average body mass index 21.4 ± 2.2 kg/m2) who took bed baths with and without (control condition: CON) AHT10s on their back. Skin temperature, heart rate variability (HRV), and blood pressure (BP) were measured. Subjective evaluations and the State-Trait Anxiety Inventory in Japanese were also performed.

Results
A significant interaction of time and bed bath type on skin surface temperature was observed (p < .001). Regarding the means of skin surface temperature at each measurement time point, those for AHT10s were significantly higher than those for CON. Although the total state-anxiety score significantly decreased in both the bed bath types after intervention, the mean values of comfort and warmth were higher for bed baths with AHT10s than for CON (p < .05) during bed baths; AHT10s was significantly higher in warmth than CON after 15 min (p = .032). The interaction and main effects of time on HRV and BP and that of bed bath type were not significant.

Conclusion
Bed baths that involved AHT10s caused participants to maintain a higher skin temperature and warmer feeling than under the wiping-only condition; they also provided comfort during the interventions. However, the bed baths with AHT10s did not allow participants to reach a relaxed state; moreover, there was no change in autonomic nerve activity. This may be due to participants’ increased anxiety from skin exposure and the intervention being limited to one part of the body.
Digital phenotyping: towards replicable findings with comprehensive assessments and integrative models in bipolar disorders
Authors: Ebner-Priemer Ulrich W. , Mühlbauer Esther , Neubauer Andreas B. , Hill Holger , Beier Fabrice , Santangelo Philip S. , Ritter Philipp , Kleindienst Nikolaus , Bauer Michael , Schmiedek Florian , Severus Emanuel 
Published: November 2020

Abstract
Background
Digital phenotyping promises to unobtrusively obtaining a continuous and objective input of symptomatology from patients’ daily lives. The prime example are bipolar disorders, as smartphone parameters directly reflect bipolar symptomatology. Empirical studies, however, have yielded inconsistent findings. We believe that three main shortcomings have to be addressed to fully leverage the potential of digital phenotyping: short assessment periods, rare outcome assessments, and an extreme fragmentation of parameters without an integrative analytical strategy.

Methods
To demonstrate how to overcome these shortcomings, we conducted frequent (biweekly) dimensional and categorical expert ratings and daily self-ratings over an extensive assessment period (12 months) in 29 patients with bipolar disorder. Digital phenotypes were monitored continuously. As an integrative analytical strategy, we used structural equation modelling to build latent psychopathological outcomes (mania, depression) and latent digital phenotype predictors (sleep, activity, communicativeness).

Outcomes
Combining gold-standard categorical expert ratings with dimensional self and expert ratings resulted in two latent outcomes (mania and depression) with statistically meaningful factor loadings that dynamically varied over 299 days. Latent digital phenotypes of sleep and activity were associated with same-day latent manic psychopathology, suggesting that psychopathological alterations in bipolar disorders relate to domains (latent variables of sleep and activity) and not only to specific behaviors (such as the number of declined incoming calls). The identification of latent psychopathological outcomes that dimensionally vary on a daily basis will enable to empirically determine which combination of digital phenotypes at which days prior to an upcoming episode are viable as digital prodromal predictors.
Two novel anticancer compounds with minimum cardiotoxic property
Authors: Afsharirad Tayebeh , Tahmasvand Raheleh , Amini Mohsen , Daraei Bahram , Salimi Mona 
Published: November 2020

AbstractBackgroundAlthough two novel synthesized compounds with tri-aryl structures; 3-(4-chlorophenyl)-5-(4-fluorophenyl)-4-phenyl-4,5-dihydro-1,2,4-oxadiazole (A) and 3,5-bis-(4-chlorophenyl)-4-phenyl-4,5-dihydro-1,2,4-oxadiazole (B) have been previously demonstrated to possess remarkable anti-breast cancer activity, their cardiotoxicity remains a major concern due to their mechanism of action. To address this concern, we assessed the ability of these compounds to cause toxicity towards H9c2 cardiomyocytes as an in vitro model of cardiotoxicity.MethodsCytotoxic activity of both compounds was explored in vitro on H9c2 cells using MTT assay. Annexin V/PI method, intracellular ROS determination and mitochondrial membrane potential assay were applied to elucidate the mechanism of action of the cell death.ResultsMTT assay revealed a concentration- and time-dependent cardiotoxicity. Findings of apoptosis by double staining with annexin V and propidium iodide divulged no cell death including apoptosis and necrosis at the concentration that were effective to inhibit cancer cells proliferation (10 μM) at 24 and 48 h. Furthermore, flow cytometric measurement of membrane potential and ROS determination using DCFH-DA verified the safe concentration of the compounds against H9c2 cells with no cardiotoxic effect. However, the higher concentration of the compounds could induce cell death through ROS-mediated mitochondrial dysfunction.ConclusionsAltogether, the results represented two novel chemical molecules possessing anti-breast cancer activity with minimum cardiac side effect.
Knockdown of lncRNA TUG1 inhibits hippocampal neuronal apoptosis and participates in aerobic exercise-alleviated vascular cognitive impairment
Authors: Wang Jing , Niu Yali , Tao Huaying , Xue Mina , Wan Chunxiao 
Published: November 2020

Abstract
Objectives
Our previous study indicated that aerobic exercise relieves cognitive impairment in patients with vascular cognitive impairment (VCI) via regulating brain-derived neurotrophic factor (BDNF), but the mechanism is not yet clear. This study aimed to explore whether lncRNA taurine upregulated gene 1 (TUG1) participates in the process of VCI by regulating BDNF.

Methods
The expressions of TUG1 and BDNF in the serum of VCI patients were detected. The potential molecular mechanisms of TUG1 in regulating hippocampal neuronal apoptosis were explored in oxygen and glucose deprivation-induced (OGD-induced) hippocampal cell line HT22. The VCI mouse model was established, and TUG1 and BDNF were overexpressed via lentivirus injection. The cognitive impairment of mice was detected by the Morris water maze experiment after the aerobic exercise.

Results
The level of TUG1 was elevated in the serum of VCI patients compared with the control group. The knockdown of TUG1 in OGD-induced HT22 cells increased BDNF level and decreased cell apoptosis, and the downregulation of BDNF restored the decreased cell apoptosis. RNA immunoprecipitation and RNA pull-down assays showed that TUG1 could bind to BDNF protein. The aerobic exercise alleviated cognitive impairment and inhibited hippocampal apoptosis in VCI mice. Meanwhile, the overexpression of TUG1 reversed the therapeutic effects of aerobic exercise on cognitive impairment.

Conclusions
The knockdown of TUG1 reduced hippocampal neuronal apoptosis and participates in the aerobic exercise-alleviated VCI, which was partly through regulating BDNF.