bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concentrations of canine prostate specific esterase, CPSE, at baseline are associated with the relative size of the prostate at three-year follow-up
Authors: Holst Bodil S. , Carlin Sofia , Fouriez-Lablée Virginie , Hanås Sofia , Ödling Sofie , Langborg Liss-Marie , Ubhayasekera S. J. Kumari A. , Bergquist Jonas , Rydén Jesper , Holmroos Elin , Hansson Kerstin 
Published: April 2021

Abstract
Background
Enlargement of the prostate is associated with prostatic diseases in dogs, and an estimation of prostatic size is a central part in the diagnostic workup. Ultrasonography is often the method of choice, but biomarkers constitute an alternative. Canine prostate specific esterase (CPSE) shares many characteristics with human prostate specific antigen (PSA) and is related to prostate size. In men with clinical symptoms of prostatic disease, PSA concentrations are related to prostate growth. The aims of the present follow-up study were to evaluate if the concentration of CPSE is associated with future growth of the prostate, and if analysis of a panel of 16 steroids gives further information on prostatic growth. Owners of dogs included in a previous study were 3 years later contacted for a follow-up study that included an interview and a clinical examination. The prostate was examined by ultrasonography. Serum concentrations of CPSE were measured, as was a panel of steroids.

Results
Of the 79 dogs included at baseline, owners of 77 dogs (97%) were reached for an interview, and 22 were available for a follow-up examination. Six of the 79 dogs had clinical signs of prostatic disease at baseline, and eight of the remaining 73 dogs (11%) developed clinical signs between baseline and follow-up, information was lacking for two dogs. Development of clinical signs was significantly more common in dogs with a relative prostate size of ≥2.5 at baseline (n = 20) than in dogs with smaller prostates (n = 51). Serum concentrations of CPSE at baseline were not associated with the change in prostatic size between baseline and follow-up. Serum concentrations of CPSE at baseline and at follow-up were positively associated with the relative prostatic size (Srel) at follow-up. Concentrations of corticosterone (P = 0.024), and the class corticosteroids (P = 0.0035) were positively associated with the difference in Srel between baseline and follow-up.

Conclusions
The results support the use of CPSE for estimating present and future prostatic size in dogs ≥4 years, and the clinical usefulness of prostatic size for predicting development of clinical signs of prostatic disease in the dog. The association between corticosteroids and prostate growth warrants further investigation.
Morphological changes in bitches endometrium affected by cystic endometrial hyperplasia - pyometra complex – the value of histopathological examination
Authors: Woźna-Wysocka Magdalena , Rybska Marta , Błaszak Beata , Jaśkowski Bartłomiej M. , Kulus Magdalena , Jaśkowski Jędrzej M. 
Published: April 2021

Abstract
Background
Cystic endometrial hyperplasia-pyometra complex (CEH-P) is one of the most common uteropathies in bitches. In diseases with mild or obscure clinical signs and normal uterine size, a diagnosis based on a clinical assessment might be incorrect.
The main aim of the research was to determine the morphological variables accompanying uterine diseases in bitches in microscopic evaluation. Consequently, the obtained results can be used to create a new classification system for uterine pathological changes during the development of the CEH-P, diagnosed by microscopic examination in bitches. Material for the study consisted of the uteri of 120 female dogs, aged 1–16 years, obtained during routine ovariohysterectomies. Macroscopic observation after a longitudinal incision of the uterine horns, allowed a preliminary classification of the uteri into research groups: control group (physiological uteri), and groups GI-III uteri collected form bitches with varying degrees of endometrial pathology. These preliminary classifications were then verified by histological analysis (H&E stain).

Results
The obtained results made it possible to determine and describe the prevalence (%) of pathological changes characteristic of the analyzed uterine diseases in the examined bitches. Histopathological analyses that were conducted have confirmed preliminary macroscopic evaluation for the control group, group GII (CEH), and group GIII (pyometra). In the uteri of the GI group, a severe congestion of the endometrium has been observed – this is typical of inflammation – which was not confirmed during histopathological examinations. However, these examinations revealed acute endometrial haemorrhage of varying severity.

Conclusions
Early reproduction disorders in bitches are, in general, not confirmed by clinical signs in the examined animals. The results show that during classification of typical morphological changes in the endometrium over the development of the CEH-P complex in bitches microscopic examinations are required. The obtained results indicate a frequent lack of consistency in the macroscopic assessment and histological analysis of the endometrium, observed in the analyzed uterine diseases, which in most cases is not followed by clinical symptoms. The presented classification of uterine diseases may be useful as a diagnostic tool in reproductive disorders in bitches and in examination in the field of basic research.
Practical application and validation of the 2018 ATS/ERS/JRS/ALAT and Fleischner Society guidelines for the diagnosis of idiopathic pulmonary fibrosis
Authors: Shih Angela R. , Nitiwarangkul Chayanin , Little Brent P. , Roop Benjamin W. , Nandy Sreyankar , Szabari Margit V. , Mercaldo Nathaniel , Mercaldo Sarah , Montesi Sydney B. , Muniappan Ashok , Berigei Sarita R. , Lynch David A. , Sharma Amita , Hariri Lida P. 
Published: April 2021

Abstract
Background
Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is essential to inform prognosis and treatment. In 2018, the ATS/ERS/JRS/ALAT and Fleischner Society released new diagnostic guidelines for usual interstitial pneumonitis (UIP)/IPF, adding Probable UIP as a CT category based on prior studies demonstrating this category had relatively high positive predictive value (PPV) for histopathologic UIP/Probable UIP. This study applies the 2018 ATS/ERS/JRS/ALAT and Fleischner Society guidelines to determine test characteristics of CT categories in academic clinical practice.

Methods
CT and histopathology were evaluated by three thoracic radiologists and two thoracic pathologists. Comparison of consensus categorization by the 2018 ATS and Fleischner Society guidelines by CT and histopathology was performed.

Results
Of patients with CT UIP, 87% (PPV, 95% CI: 60–98%) had histopathologic UIP with 97% (CI: 90–100%) specificity. Of patients with CT Probable UIP, 38% (PPV, CI: 14–68%) had histopathologic UIP and 46% (PPV, CI: 19–75%) had either histopathologic UIP or Probable UIP, with 88% (CI: 77–95%) specificity. Patients with CT Indeterminate and Alternative Diagnosis had histopathologic UIP in 27% (PPV, CI: 6–61%) and 21% (PPV, CI: 11–33%) of cases with specificities of 90% (CI: 80–96%) and 25% (CI: 16–37%). Interobserver variability (kappa) between radiologists ranged 0.32–0.81.

Conclusions
CT UIP and Probable UIP have high specificity for histopathologic UIP, and CT UIP has high PPV for histopathologic UIP. PPV of CT Probable UIP was 46% for combined histopathologic UIP/Probable UIP. Our results indicate that additional studies are needed to further assess and refine the guideline criteria to improve classification performance.
Portable NIV for patients with moderate to severe COPD: two randomized crossover trials
Authors: Majorski Daniel Sebastian , Magnet Friederike Sophie , Thilemann Saadia , Schmoor Claudia , Windisch Wolfram , Schwarz Sarah Bettina 
Published: April 2021

Abstract
Background
Long-term non-invasive ventilation (NIV) is as an established treatment option for chronic hypercapnic COPD patients. Beneficial effects have also been shown during exercise, but this is restricted to rehabilitation programs. New portable NIV (pNIV) devices may now enable NIV application during walking at home.

Study design and methods
In two randomized crossover trials, the impact of pNIV on dyspnea and endurance capacity was investigated in patients with moderate to severe COPD. Participants performed a standardized 6-min walking test, with and without pNIV, using a pre-set inspiratory/expiratory positive airway pressure of 18/8 cmH2O. The first study was performed in NIV-naïve patients (Study I), while the second study was performed in those already established on long-term NIV (Study II).

Results
38 patients (66.9 ± 7.4 years, mean FEV1: 30.3 ± 8%pred) and 23 patients (67.6 ± 8.7 years, mean FEV1: 29.8 ± 10.4%pred) participated in Study I and II, respectively. In Study I, the mean difference in the Borg Dyspnea Scale (BDS, primary outcome) score following walking was 3.2 (IQR 2–4) without pNIV, compared to 2.6 (IQR 1–4) with pNIV (ΔBDS 0.65, P = 0.04), while walking distance increased from 311.8 m (95%CI 276.9–346.6 m) to 326.3 m (95%CI 291.5–361.2 m) (P = 0.044) when pNIV was used. Accordingly, in Study II, the mean difference in BDS was 4.4 (IQR 3–6) without pNIV, compared to 4.5 (IQR 3–6) with pNIV (ΔBDS 0.09, P = 0.54), while walking distance decreased from 291.5 m (95%CI 246.1–336.9 m) to 258.4 m (95%CI 213–303.8 m) (P ≤ 0.001).

Interpretation
The use of a pNIV device during walking can improve dyspnea and walking distance in patients with moderate to severe COPD. Patients who do not already receive long-term NIV therapy are more likely to benefit compared to those undergoing long-term NIV. Careful patient selection is mandatory.
Clinical Trial Register: DRKS00013203; DRKS00012913 registered October 20th 2017 and October 16th 2017; https://www.drks.de/drks_web/
The role of RNA m6A methylation in the regulation of postnatal hypoxia-induced pulmonary hypertension
Authors: Xu Shanshan , Xu Xuefeng , Zhang Ziming , Yan Lingling , Zhang Liyan , Du Lizhong 
Published: April 2021

Abstract
Background
Pulmonary hypertension (PH) is a complex pulmonary vascular disease characterized by an imbalance in vasoconstrictor/vasodilator signaling within the pulmonary vasculature. Recent evidence suggests that exposure to hypoxia early in life can cause alterations in the pulmonary vasculature and lead to the development of PH. However, the long-term impact of postnatal hypoxia on lung development and pulmonary function remains unknown. N6-methyladenosine (m6A) regulates gene expression and governs many important biological processes. However, the function of m6A in the development of PH remains poorly characterized. Thus, the purpose of this investigation was to test the two-fold hypothesis that (1) postnatal exposure to hypoxia would alter lung development leading to PH in adult rats, and (2) m6A modification would change in rats exposed to hypoxia, suggesting it plays a role in the development of PH.

Methods
Twenty-four male Sprague–Dawley rats were exposed to a hypoxic environment (FiO2: 12%) within 24 h after birth for 2 weeks. PH was defined as an increased right ventricular pressure (RVP) and pathologic changes of pulmonary vasculature measured by α-SMA immunohistochemical staining. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was performed to analyze m6A modification changes in lung tissue in 2- and 9-week-old rats that were exposed to postnatal hypoxia.

Results
Mean pulmonary arterial pressure, lung/body weight ratio, and the Fulton index was significantly greater in rats exposed to hypoxia when compared to control and the difference persisted into adulthood. m6A methyltransferase and demethylase proteins were significantly downregulated in postnatal hypoxia-induced PH. Distinct m6A modification peak-related genes differed between the two groups, and these genes were associated with lung development.

Conclusions
Our results indicate postnatal hypoxia can cause PH, which can persist into adulthood. The development and persistence of PH may be because of the continuous low expression of methyltransferase like 3 affecting the m6A level of PH-related genes. Our findings provide new insights into the impact of postnatal hypoxia and the role of m6A in the development of pulmonary vascular pathophysiology.
The VIM-AS1/miR-655/ZEB1 axis modulates bladder cancer cell metastasis by regulating epithelial–mesenchymal transition
Authors: Xiong Yaoyao , Zu Xiongbing , Wang Long , Li Yuan , Chen Minfeng , He Wei , Qi Lin 
Published: April 2021

Abstract
Background
Invasive bladder tumors cause a worse prognosis in patients and remain a clinical challenge. Epithelial–mesenchymal transition (EMT) is associated with bladder cancer metastasis. In the present research, we attempted to demonstrate a novel mechanism by which a long noncoding RNA (lncRNA)-miRNA-mRNA axis regulates EMT and metastasis in bladder cancer.

Methods
Immunofluorescence (IF) staining was used to detect Vimentin expression. The protein expression of ZEB1, Vimentin, E-cadherin, and Snail was investigated by using immunoblotting assays. Transwell assays were performed to detect the invasive capacity of bladder cancer cells. A wound healing assay was used to measure the migratory capacity of bladder cancer cells.

Results
Herein, we identified lncRNA VIM-AS1 as a highly- expressed lncRNA in bladder cancer, especially in metastatic bladder cancer tissues and high-metastatic bladder cancer cell lines. By acting as a ceRNA for miR-655, VIM-AS1 competed with ZEB1 for miR-655 binding, therefore eliminating the miR-655-mediated suppression of ZEB1, finally promoting EMT in both high- and low-metastatic bladder cancer cells and enhancing cancer cell metastasis.

Conclusions
In conclusion, the VIM-AS1/miR-655/ZEB1 axis might be a promising target for improving bladder cancer metastasis via an EMT-related mechanism.
LINC01783 facilitates cell proliferation, migration and invasion in non-small cell lung cancer by targeting miR-432-5p to activate the notch pathway
Authors: Deng Yanchao , Zhang Liwei , Luo Ruiying 
Published: April 2021

Abstract
Background
Non-small cell lung cancer (NSCLC) is a common malignancy around the globe. Increasing long non-coding RNAs (lncRNAs) have been confirmed to be associated with the progression of cancers, including NSCLC. Long intergenic non-protein coding RNA 1783 (LINC01783) is a novel lncRNA and its regulatory function as competing endogenous RNA (ceRNA) has not been studied in NSCLC.

Methods
RT-qPCR measured the expression level of LINC01783 in NSCLC cells. CCK-8, EdU, transwell and wound healing assays were conducted to detect cell proliferation, migration and invasion in NSCLC. The relationship between miR-432-5p and LINC01783 along with delta like 1 (DLL-1) was illustrated by RNA pull down, RIP and luciferase reporter assays.

Results
LINC01783 was found remarkably increased in NSCLC cell lines, and down-regulation of LINC01783 suppressed cell proliferation, migration and invasion. Then, we discovered Notch pathway was related to the progression of NSCLC, and DLL-1 expression was reduced by LINC01783 knockdown. Furthermore, DLL-1 overexpression could counteract the suppressive effects of LINC01783 down-regulation on the growth of NSCLC cells. MiR-432-5p was observed to be the mutual miRNA that could bind with both LINC01783 and DLL-1. Overexpression of miR-432-5p inhibited DLL-1 expression. In the rescue assays, miR-432-5p depletion offset the impacts of LINC01783 knockdown, and then DLL-1 silence recovered the influence of miR-432-5p down-regulation on NSCLC cell growth.

Conclusion
LINC01783 aggravates NSCLC cell growth by regulating Notch pathway and sponging miR-432-5p, being a potential target in the treatment for NSCLC.
Minocycline attenuation of rat corpus callosum abnormality mediated by low-dose lipopolysaccharide-induced microglia activation
Authors: Zhang Jingdong , Boska Michael , Zheng Ya , Liu Jianuo , Fox Howard S. , Xiong Huangui 
Published: April 2021

AbstractBackgroundMicroglia are resident innate immune cells in the brain, and activation of these myeloid cells results in secretion of a variety of pro-inflammatory molecules, leading to the development of neurodegenerative disorders. Lipopolysaccharide (LPS) is a widely used experimental stimulant in microglia activation. We have previously shown that LPS produced microglia activation and evoked detectable functional abnormalities in rat corpus callosum (CC) in vitro. Here, we further validated the effects of low-dose LPS-induced microglia activation and resultant white matter abnormality in the CC in an animal model and examined its attenuation by an anti-inflammatory agent minocycline.MethodsTwenty-four SD rats were divided randomly into three groups and intra-peritoneally injected daily with saline, LPS, and LPS + minocycline, respectively. All animals were subject to MRI tests 6 days post-injection. The animals were then sacrificed to harvest the CC tissues for electrophysiology, western blotting, and immunocytochemistry. One-way ANOVA with Tukey’s post-test of all pair of columns was employed statistical analyses.ResultsSystemic administration of LPS produced microglial activation in the CC as illustrated by Iba-1 immunofluorescent staining. We observed that a large number of Iba-1-positive microglial cells were hyper-ramified with hypertrophic somata or even amoeba like in the LPS-treated animals, and such changes were significantly reduced by co-administration of minocycline. Electrophysiological recordings of axonal compound action potential (CAP) in the brain slices contained the CC revealed an impairment on the CC functionality as detected by a reduction in CAP magnitude. Such an impairment was supported by a reduction of fast axonal transportation evidenced by β-amyloid precursor protein accumulation. These alterations were attenuated by minocycline, demonstrating minocycline reduction of microglia-mediated interruption of white matter integrity and function in the CC.ConclusionsSystemic administration of LPS produced microglia activation in the CC and resultant functional abnormalities that were attenuated by an anti-inflammatory agent minocycline.
Impact of strategic use of antiretroviral therapy intervention to the HIV continuum of care in 13 cities in Indonesia: an interrupted time series analysis
Authors: Tarigan Yane N. , Woodman Richard J. , Miller Emma R. , Wisaksana Rudi , Ward Paul R. 
Published: April 2021

Abstract
Background
In 2013 the Indonesian government introduced the strategic use of antiretroviral therapy (SUFA) initiative of expanding access to HIV test and treatment, to help achieve the UNAIDS 90–90–90 targets. However, there has been no comprehensive evaluation of the impact of this intervention in Indonesia. We conducted an interrupted time series (ITS) analysis across 6-years to assess its immediate and medium-term impact.

Methods
Monthly aggregated HIV data from all HIV care clinics for persons aged ≥ 15 years were collected from 13 pilot cities. The data period encompassed 3-years prior to SUFA (26 Dec 2010–25 Dec 2013) and 3-years post-SUFA (26 Dec 2013–25 Dec 2016). The ITS was performed using a multilevel negative binomial regression model to assess the immediate and trend changes in each stage of the HIV continuum of care.

Results
In the pre-SUFA period, the overall coverage in the respective risk populations for HIV tests, cases, enrolments, eligible cases and ARV initiation were 1.0%, 8.6%, 98.9%, 76.9% and 75.8% respectively. In the post-SUFA period coverage was 3%, 3.8%, 98.6%, 90.3% and 81.2% respectively—with a significant increase in the median number of HIV tests, HIV cases, those eligible for ARV treatment and treatment initiation (p < 0.05 for each). The ITS analysis demonstrated immediate increases in HIV tests (IRR = 1.41, 95% CI 1.25, 1.59; p < 0.001) and an immediate decrease in detected HIV cases per person tested (IRR = 0.77, 95% CI 0.69–0.86; p < 0.001) in the month following commencement of SUFA. There was also a 3% decline in the monthly trend for HIV tests performed (IRR = 0.97; 95% CI 0.97–0.98, p < 0.001), a 1% increase for detected cases (IRR = 1.01, 95% CI 1.0–1.02, p < 0.001), and a 1% decline for treatment initiation (IRR = 0.99,95% CI 0.99–1.0 p < 0.05).

Conclusions
SUFA was associated with an immediate and sustained increase in the absolute number of HIV tests performed, detected HIV cases, and close to complete coverage of detected cases that were enrolled to care and defined as eligible for treatment. However, treatment initiation remained sub-optimal. The findings of this study provide valuable information on the real-world effect of accelerating ARV utilizing Treatment as Prevention for the full HIV continuum of care in limited resource countries.
Functional morphology of immature mating in a widow spider
Authors: Sentenská Lenka , Neumann Aileen , Lubin Yael , Uhl Gabriele 
Published: April 2021

Abstract
Background
Mating generally occurs after individuals reach adulthood. In many arthropods including spiders, the adult stage is marked by a final moult after which the genitalia are fully developed and functional. In several widow spider species (genus Latrodectus), however, immature females may mate a few days before they moult to adulthood, i.e. in their late-subadult stage. While the “adult” mating typically results in cannibalism, males survive the “immature” mating. During both “immature” and “adult” matings, males leave parts of their paired copulatory organs within female genitalia, which may act as mating plugs. To study potential costs and benefits of the two mating tactics, we investigated female genital morphology of the brown widow spider, L. geometricus. Light microscopy, histology and micro-computed tomography of early-subadult, late-subadult and adult females were conducted to determine the overall pattern of genital maturation. We compared genitalia of mated late-subadult and adult females to reveal potential differences in the genitalic details that might indicate differential success in sperm transfer and different environments for sperm storage and sperm competition.

Results
We found that the paired sperm storage organs (spermathecae) and copulatory ducts are developed already in late-subadult females and host sperm after immature mating. However, the thickness of the spermathecal cuticle and the staining of the secretions inside differ significantly between the late-subadult and adult females. In late-subadult females mating plugs were found with higher probability in both spermathecae compared to adult females.

Conclusions
Sperm transfer in matings with late-subadult females follows the same route as in matings with adult females. The observed differences in the secretions inside the spermathecae of adult and late-subadult females likely reflect different storage conditions for the transferred sperm which may lead to a disadvantage under sperm competition if the subadult female later re-mates with another male. However, since males mating with late-subadult females typically transfer sperm to both spermathecae they might benefit from numerical sperm competition as well as from monopolizing access to the female sperm storage organs. The assessment of re-mating probability and relative paternity will clarify the costs and benefits of the two mating tactics in light of these findings.