bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study
Authors: Niwamoto Takafumi , Handa Tomohiro , Murase Yuko , Nakatsuka Yoshinari , Tanizawa Kiminobu , Taguchi Yoshio , Tomioka Hiromi , Tomii Keisuke , Kita Hideo , Uyama Michihiro , Tsuchiya Michiko , Emura Masahito , Kawamura Tetsuji , Arai Naoki , Arita Machiko , Uno Kazuko , Yoshizawa Akihiko , Uozumi Ryuji , Yamaguchi Izumi , Matsuda Fumihiko , Chin Kazuo , Hirai Toyohiro 
Published: June 2021

AbstractBackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not possible. This study aimed to evaluate serum cytokines/chemokines as potential biomarkers that can predict outcomes in IPF patients.MethodsA multi-institutional prospective two-stage discovery and validation design using two independent cohorts was adopted. For the discovery analysis, serum samples from 100 IPF patients and 32 healthy controls were examined using an unbiased, multiplex immunoassay of 48 cytokines/chemokines. The serum cytokine/chemokine values were compared between IPF patients and controls; the association between multiplex measurements and survival time was evaluated in IPF patients. In the validation analysis, the cytokines/chemokines identified in the discovery analysis were examined in serum samples from another 81 IPF patients to verify the ability of these cytokines/chemokines to predict survival. Immunohistochemical assessment of IPF-derived lung samples was also performed to determine where this novel biomarker is expressed.ResultsIn the discovery cohort, 18 cytokines/chemokines were significantly elevated in sera from IPF patients compared with those from controls. Interleukin-1 receptor alpha (IL-1Rα), interleukin-8 (IL-8), macrophage inflammatory protein 1 alpha (MIP-1α), and cutaneous T-cell-attracting chemokine (CTACK) were associated with survival: IL-1Rα, hazard ratio (HR) = 1.04 per 10 units, 95% confidence interval (95% CI) 1.01–1.07; IL-8, HR = 1.04, 95% CI 1.01–1.08; MIP-1α, HR = 1.19, 95% CI 1.00–1.36; and CTACK, HR = 1.12 per 100 units, 95% CI 1.02–1.21. A replication analysis was performed only for CTACK because others were previously reported to be potential biomarkers of interstitial lung diseases. In the validation cohort, CTACK was associated with survival: HR = 1.14 per 100 units, 95% CI 1.01–1.28. Immunohistochemistry revealed the expression of CTACK and CC chemokine receptor 10 (a ligand of CTACK) in airway and type II alveolar epithelial cells of IPF patients but not in those of controls.ConclusionsCTACK is a novel prognostic biomarker of IPF.Trial registrationNone (because of no healthcare intervention)
Aging and high-fat diet feeding lead to peripheral insulin resistance and sex-dependent changes in brain of mouse model of tau pathology THY-Tau22
Authors: Kacířová Miroslava , Železná Blanka , Blažková Michaela , Holubová Martina , Popelová Andrea , Kuneš Jaroslav , Šedivá Blanka , Maletínská Lenka 
Published: June 2021

Abstract
Background
Obesity leads to low-grade inflammation in the adipose tissue and liver and neuroinflammation in the brain. Obesity-induced insulin resistance (IR) and neuroinflammation seem to intensify neurodegeneration including Alzheimer’s disease. In this study, the impact of high-fat (HF) diet-induced obesity on potential neuroinflammation and peripheral IR was tested separately in males and females of THY-Tau22 mice, a model of tau pathology expressing mutated human tau protein.

Methods
Three-, 7-, and 11-month-old THY-Tau22 and wild-type males and females were tested for mobility, anxiety-like behavior, and short-term spatial memory in open-field and Y-maze tests. Plasma insulin, free fatty acid, cholesterol, and leptin were evaluated with commercial assays. Liver was stained with hematoxylin and eosin for histology. Brain sections were 3′,3′-diaminobenzidine (DAB) and/or fluorescently detected for ionized calcium-binding adapter molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and tau phosphorylated at T231 (pTau (T231)), and analyzed. Insulin signaling cascade, pTau, extracellular signal-regulated kinase 1/2 (ERK1/2), and protein phosphatase 2A (PP2A) were quantified by western blotting of hippocampi of 11-month-old mice. Data are mean ± SEM and were subjected to Mann-Whitney t test within age and sex and mixed-effects analysis and Bonferroni’s post hoc test for age comparison.

Results
Increased age most potently decreased mobility and increased anxiety in all mice. THY-Tau22 males showed impaired short-term spatial memory. HF diet increased body, fat, and liver weights and peripheral IR. HF diet-fed THY-Tau22 males showed massive Iba1+ microgliosis and GFAP+ astrocytosis in the hippocampus and amygdala. Activated astrocytes colocalized with pTau (T231) in THY-Tau22, although no significant difference in hippocampal tau phosphorylation was observed between 11-month-old HF and standard diet-fed THY-Tau22 mice. Eleven-month-old THY-Tau22 females, but not males, on both diets showed decreased synaptic and postsynaptic plasticity.

Conclusions
Significant sex differences in neurodegenerative signs were found in THY-Tau22. Impaired short-term spatial memory was observed in 11-month-old THY-tau22 males but not females, which corresponded to increased neuroinflammation colocalized with pTau(T231) in the hippocampi and amygdalae of THY-Tau22 males. A robust decrease in synaptic and postsynaptic plasticity was observed in 11-month-old females but not males. HF diet caused peripheral but not central IR in mice of both sexes.
Timber identification of Autranella, Baillonella and Tieghemella in the taxonomically challenging Sapotaceae family
Authors: Deklerck V. , Price E. , Vanden Abeele S. , Lievens K. , Espinoza E. , Beeckman H. 
Published: June 2021

Abstract
Background
To enforce timber import laws and perform timber species identification, the identity of the botanical species must be well-defined. Since the Sapotaceae family is known as a taxonomically challenging family, we focus in this study on the four most valuable Sapotaceae timber species from tropical Africa: Autranella congolensis (De Wild.) A.Chev., Baillonella toxisperma Pierre, Tieghemella africana Pierre and Tieghemella heckelii (A.Chev.) Pierre ex Dubard. The wood anatomical characteristic fiber lumen fraction and Direct Analysis in Real Time—Time of Flight Mass Spectrometry (DART-TOFMS) were used to differentiate the four species and to make inferences on species delineation and taxonomic identity.

Results
We observed differences in the fiber lumen fraction measurements and discerned two groups: (1) A. congolensis and B. toxisperma, and (2) T. africana and T. heckelii. In addition, all Mann–Whitney U comparisons and differences in distributions (Kolmogorov–Smirnov) for the fiber lumen fraction measurements were significant between all species. When permutating the data between species within those two groups, significant differences were still found between the species within those groups. This could indicate that the fiber lumen fraction is not diagnostic to discern the species. DART-TOFMS analysis showed that A. congolensis and B. toxisperma have distinct chemotypes, while T. heckelii and T. africana have remarkably similar chemotypes.

Conclusions
Based on our observations of similar chemotype and weakly differentiated fiber lumen ratio, we support an alternative taxonomic hypothesis that considers Tieghemella monotypic, because of the strong resemblance between T. heckelii and T. africana. Larger sample sizes and further research is required to develop methodology for the identification of these species. A taxonomic study utilizing molecular genetics would be beneficial to assess the status of the genus and the species limits. This could have implications towards their potential inclusion on CITES appendices if there is ever need for them to be listed. If Tieghemella africana and T. heckelii remain two distinct species, they should both be listed. Screening agents should be aware that the morphological and chemical differences between T. africana and T. heckelii are minimal.
Role of hippocampal location and radiation dose in glioblastoma patients with hippocampal atrophy
Authors: Le Fèvre Clara , Cheng Xue , Loit Marie-Pierre , Keller Audrey , Cebula Hélène , Antoni Delphine , Thiery Alicia , Constans Jean-Marc , Proust François , Noel Georges 
Published: June 2021

Abstract
Background
The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma.

Methods
All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was < 7.4 Gy, in the group 2 (n = 13), only the Hcontra D40% was < 7.4 Gy, and in the group 3 (n = 30), the D40% for both hippocampi was > 7.4 Gy.

Results
Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall.

Conclusions
There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved.
Trial registration Retrospectively registered.
T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathway
Authors: Cong Shan , Meng Yan , Wang Lingrui , Sun Jiao , shi·Nu er xia ti Ta bu , Luo Li 
Published: June 2021

Abstract
Background
The aim of this study was to investigate the effect of Iguratimod (T-614) on rat knee osteoarthritis (KOA) and further to explore its underlying mechanism.

Methods
In this study, papain-induced KOA model was constructed. Hematoxylin and eosin (H&E) staining was conducted to observe the pathological changes of cartilage tissue and Mankin scoring principle was used for quantitative scoring. Transmission electron microscopy (TEM) was applied to observe the ultrastructure of cartilage tissue. ELISA was used to measure the levels of matrix metalloproteinase 13 (MMP-13) and inflammatory factors (interleukin (IL)-6 and tumor necrosis factor a (TNF-a)) in serum. RT-qPCR and immunohistochemistry were conducted to detect mRNA expression and protein expression of key genes in Wnt/β-catenin pathway.

Results
H&E, Mankin scoring, and TEM data confirmed that compared with model group, T-614 significantly improved the degeneration of articular cartilage. Besides, we observed that low, middle, and high doses of T-614 could decrease the levels of MMP13, TNF-α, and IL-6 in serum to different degrees. Mechanically, T-614 downregulated the mRNA and protein expression of β-catenin and MMP13 in cartilage tissue via a dose-dependent manner, and on the contrary upregulated the mRNA and protein expression of glucogen synthase kinase-3 beta (GSK-3β).

Conclusion
Our results suggested that T-614 can reduce the level of its downstream target gene MMP-13 and downregulate the expression of inflammatory cytokines TNF-α and IL-6 by regulating the Wnt/β-catenin signaling pathway, thereby inhibiting joint inflammation and controlling KOA degeneration of articular cartilage.
LncRNA CASC19 accelerates chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis
Authors: Zhou Chang , He Tianda , Chen Liji 
Published: June 2021

Abstract
Background
Osteoarthritis (OA) is one kind of degenerative joint disease that happens in articular cartilage and other joint tissues. Long non-coding RNAs (lncRNAs) have been reported to serve as pivotal regulators in many diseases, including OA. However, the role and relevant regulatory mechanisms of CASC19 in OA remain unknown.

Methods
The expression levels of CASC19, miR-152-3p, and DDX6 were identified by reverse-transcription polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The relationship between miR-152-3p and CASC19 or DDX6 was predicted by bioinformatics tools and verified by the dual-luciferase reporter assay.

Results
CASC19 was verified to exhibit higher expression in OA tissues and cells. Moreover, inhibition of CASC19 weakened proinflammatory cytokine (IL-6, IL-8, and TNF-α) production and cell apoptosis but facilitated cell viability. Experiments of the ceRNA mechanism elucidated that miR-152-3p was a sponge for CASC19, and miR-152-3p targeted DDX6, suggesting that CASC19 sponged miR-152-3p to release DDX6. Finally, results from rescue assays proved that the impacts of CASC19 silencing on chondrocytes apoptosis and proinflammatory cytokine production could be reversed by DDX6 overexpression.

Conclusions
It was concluded that lncRNA CASC19 accelerated chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis. These findings may offer an effective biological target for OA treatment.
Impact of body mass index on early and mid-term outcomes after surgery for acute Stanford type A aortic dissection
Authors: Liu Yanxiang , Zhang Bowen , Liang Shenghua , Dun Yaojun , Wang Luchen , Gao Haoyu , Ren Jie , Guo Hongwei , Sun Xiaogang 
Published: June 2021

Abstract
Background
Obesity is dramatically increasing worldwide, and more obese patients may develop aortic dissection and present for surgical repair. The study aims to analyse the impact of body mass index (BMI) on surgical outcomes in patients with acute Stanford type A aortic dissection (ATAAD).

Methods
From January 2017 to June 2019, the clinical data of 268 ATAAD patients in a single centre were retrospectively reviewed. They were divided into three groups based on the BMI: normal weight (BMI 18.5 to < 25 kg/m2, n = 110), overweight (BMI 25 to < 30 kg/m2, n = 114) and obese (BMI ≥30 kg/m2, n = 44).

Results
There was no statistical difference among the three groups in terms of the composite adverse events including 30-day mortality, stroke, paraplegia, renal failure, hepatic failure, reintubation or tracheotomy and low cardiac output syndrome (20.9% vs 21.9% vs 18.2% for normal, overweight and obese, respectively; P = 0.882). No significant difference was found in the mid-term survival among the three groups. The proportion of prolonged ventilation was highest in the obese group followed by the overweight and normal groups (59.1% vs 45.6% vs 34.5%, respectively; P = 0.017). Multivariable logistic regression analysis suggested that BMI was not associated with the composite adverse events, while BMI ≥30 kg/m2 was an independent risk factor for prolonged ventilation (OR 2.261; 95% CI 1.056–4.838; P = 0.036).

Conclusions
BMI had no effect on the early major adverse outcomes and mid-term survival after surgery for ATAAD. Satisfactory surgical outcomes can be obtained in patients with ATAAD at all weights.
SARS-CoV-2 quantitative real time PCR and viral loads analysis among asymptomatic and symptomatic patients: an observational study on an outbreak in two nursing facilities in Campania Region (Southern Italy)
Authors: Cardillo Lorena , de Martinis Claudio , Viscardi Maurizio , Esposito Claudia , Sannino Emanuela , Lucibelli Gabriella , Limone Antonio , Pellino Stefania , Anastasio Rosa , Pellicanò Roberta , Baldi Loredana , Galiero Giorgio , Fusco Giovanna 
Published: June 2021

Abstract
Background
In December 2019 an outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 was first observed in Wuhan, China. The virus has spread rapidly throughout the world creating a pandemic scenario. Several risk factors have been identified, such as age, sex, concomitant diseases as well as viral load. A key point is the role of asymptomatic people in spreading SARS-CoV-2. An observational study in Southern Italy was conducted in order to elucidate the possible role of asymptomatic individuals related to their viral loads in the transmission of the virus within two nursing facilities.

Methods
Oro-nasopharyngeal swabs from 179 nursing health care workers and patients were collected. SARS-CoV-2 RT-qPCR was performed and viral loads were calculated by using standard curve. A statistical correlation between viral loads, the presence/absence of symptoms, age and sex variables was investigated.

Results
SARS-CoV-2 was confirmed in the 50.8 % (n = 91) of the cases. Median age of positive individuals resulted higher than negative ones. Over 65 year as well as female individuals showed higher susceptibility to SARS-CoV-2 infection, OR = 3.93 and 2.86, respectively. Among 91 tested positive, the 70.3 % was symptomatic while the 29.7 % was asymptomatic. Median viral loads of asymptomatic individuals were found statistically significant higher than symptomatic ones (p = 0.001), while no influence was observed in age and sex variables. The presence of comorbidities was 8.9 folds higher in patients who showed and developed symptoms compared to non-symptomatic ones. Moreover, higher viral loads were found in patients who remained asymptomatic than pre-symptomatic (p = 0.022).

Conclusions
A range from 9.2 to 69 % of confirmed SARS-CoV-2 cases remains asymptomatic, moreover, sporadic transmissions from asymptomatic people are reported, that makes their involvement an important issue to take into account in the spreading control of the virus. An asymptomatic clinical course was observed in the 29.7 % of positive individuals, moreover, median viral loads resulted to be statistically significant when compared to symptomatic ones. Surely, such a relevant frequency should not be ignored in relation to the spread of the disease in an environment which has not only important intrinsic (age, sex, concomitant diseases) but also extrinsic factors such as high population density and close contacts.
Enzymatic hydrolysis of the gelatinous layer in tension wood of Salix varieties as a measure of accessible cellulose for biofuels
Authors: Gao Jie , Jebrane Mohamed , Terziev Nasko , Daniel Geoffrey 
Published: June 2021

Abstract
Background
Salix (willow) species represent an important source of bioenergy and offer great potential for producing biofuels. Salix spp. like many hardwoods, produce tension wood (TW) characterized by special fibres (G-fibres) that produce a cellulose-rich lignin-free gelatinous (G) layer on the inner fibre cell wall. Presence of increased amounts of TW and G-fibres represents an increased source of cellulose. In the present study, the presence of TW in whole stems of different Salix varieties was characterized (i.e., physical measurements, histochemistry, image analysis, and microscopy) as a possible marker for the availability of freely available cellulose and potential for releasing d-glucose. Stem cross sections from different Salix varieties (Tora, Björn) were characterized for TW, and subjected to cellulase hydrolysis with the free d-glucose produced determined using a glucose oxidase/peroxidase (GOPOD) assay. Effect of cellulase on the cross sections and progressive hydrolysis of the G-layer was followed using light microscopy after staining and scanning electron microscopy (SEM).

Results
Tension wood fibres with G-layers were developed multilaterally in all stems studied. Salix TW from varieties Tora and Björn showed fibre G-layers were non-lignified with variable thickness. Results showed: (i) Differences in total % TW at different stem heights; (ii) that using a 3-day incubation period at 50 °C, the G-layers could be hydrolyzed with no apparent ultrastructural effects on lignified secondary cell wall layers and middle lamellae of other cell elements; and (iii) that by correlating the amount of d-glucose produced from cross sections at different stem heights together with total % TW and density, an estimate of the total free d-glucose in stems can be derived and compared between varieties. These values were used together with a literature value (45%) for estimating the contribution played by G-layer cellulose to the total cellulose content.

Conclusions
The stem section-enzyme method developed provides a viable approach to compare different Salix varieties ability to produce TW and thus freely available d-glucose for fermentation and biofuel production. The use of Salix stem cross sections rather than comminuted biomass allows direct correlation between tissue- and cell types with d-glucose release. Results allowed correlation between % TW in cross sections and entire Salix stems with d-glucose production from digested G-layers. Results further emphasize the importance of TW and G-fibre cellulose as an important marker for enhanced d-glucose release in Salix varieties.