bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol for a randomized, placebo-controlled, and multicenter trial
Authors: Boesing Maria , Abig Kristin , Brändle Michael , Brutsche Martin , Burri Emanuel , Frye Björn C. , Giezendanner Stéphanie , Grutters Jan C. , Haas Philippe , Heisler Justian , Jaun Fabienne , Leuppi-Taegtmeyer Anne B. , Lüthi-Corridori Giorgia , Müller-Quernheim Joachim , Nüesch Reto , Pohl Wolfgang , Rassouli Frank , Leuppi Jörg D. 
Published: September 2022

AbstractBackgroundDespite the fast establishment of new therapeutic agents in the management of COVID-19 and large-scale vaccination campaigns since the beginning of the SARS-CoV-2 pandemic in early 2020, severe disease courses still represent a threat, especially to patients with risk factors. This indicates the need for alternative strategies to prevent respiratory complications like acute respiratory distress syndrome (ARDS) associated with COVID-19. Aviptadil, a synthetic form of human vasoactive intestinal peptide, might be beneficial for COVID-19 patients at high risk of developing ARDS because of its ability to influence the regulation of exaggerated pro-inflammatory proteins and orchestrate the lung homeostasis. Aviptadil has recently been shown to considerably improve the prognosis of ARDS in COVID-19 when applied intravenously. An inhaled application of aviptadil has the advantages of achieving a higher concentration in the lung tissue, fast onset of activity, avoiding the hepatic first-pass metabolism, and the reduction of adverse effects. The overall objective of this project is to assess the efficacy and safety of inhaled aviptadil in patients hospitalized for COVID-19 at high risk of developing ARDS.MethodsThis multicenter, placebo-controlled, double-blinded, randomized trial with 132 adult patients hospitalized for COVID-19 and at high risk for ARDS (adapted early acute lung injury score ≥ 2 points) is conducted in five public hospitals in Europe. Key exclusion criteria are mechanical ventilation at baseline, need for intensive care at baseline, and severe hemodynamic instability. Patients are randomly allocated to either inhale 67 μg aviptadil or normal saline (three times a day for 10 days), in addition to standard care, stratified by center. The primary endpoint is time from hospitalization to clinical improvement, defined as either hospital discharge, or improvement of at least two levels on the nine-level scale for clinical status suggested by the World Health Organization.DiscussionTreatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19.Trial registrationClinicalTrials.gov,NCT04536350. Registered 02 September 2020.
Regional gain and global loss of 5-hydroxymethylcytosine coexist in genitourinary cancers and regulate different oncogenic pathways
Authors: Qi Jie , Shi Yue , Tan Yezhen , Zhang Qi , Zhang Jianye , Wang Jilu , Huang Cong , Ci Weimin 
Published: September 2022

Abstract
Background
DNA 5-hydroxymethylcytosine (5hmC) is produced by dynamic 5mC oxidation process contributing to tissue specification, and loss of 5hmC has been reported in multiple cancers including genitourinary cancers. However, 5hmC is also cell-type specific, and its variability may exist between differentiated tumor cells and cancer stem cells. Thus, cancer-associated changes in 5hmC may be contributed by distinct sets of tumor cells within the tumor tissues.

Results
Here, we applied a sensitive immunoprecipitation-based method (hMeDIP-seq) to analyze 5hmC changes during genitourinary carcinogenesis (including prostate, urothelial and kidney). We confirmed the tissue-specific distribution of 5hmC in genitourinary tissues and identified regional gain and global loss of 5hmC coexisting in genitourinary cancers. The genes with gain of 5hmC during tumorigenesis were functionally enriched in regulating stemness and hypoxia, whereas were associated with poor clinical prognosis irrespective of their differences in tumor type. We identified that gain of 5hmC occurred in soft fibrin gel-induced 3D tumor spheres with a tumor-repopulating phenotype in two prostate cancer cell lines, 22RV1 and PC3, compared with conventional two-dimensional (2D) rigid dishes. Then, we defined a malignant signature derived from the differentially hydroxymethylated regions affected genes of cancer stem-like cells, which could predict a worse clinical outcome and identified phenotypically malignant populations of cells from prostate cancer tumors. Notably, an oxidation-resistant vitamin C derivative, ascorbyl phosphate magnesium, restored 5hmC and killed the cancer stem cell-like cells leading to apoptosis in prostate cancer cell lines.

Conclusions
Collectively, our study dissects the regional gain of 5hmC in maintaining cancer stem-like cells and related to poor prognosis, which provides proof of concept for an epigenetic differentiation therapy with vitamin C by 5hmC reprogramming.

Graphic Abstract
Identification of reindeer fine-scale foraging behaviour using tri-axial accelerometer data
Authors: Rautiainen Heidi , Alam Moudud , Blackwell Paul G. , Skarin Anna 
Published: September 2022

AbstractAnimal behavioural responses to the environment ultimately affect their survival. Monitoring animal fine-scale behaviour may improve understanding of animal functional response to the environment and provide an important indicator of the welfare of both wild and domesticated species. In this study, we illustrate the application of collar-attached acceleration sensors for investigating reindeer fine-scale behaviour. Using data from 19 reindeer, we tested the supervised machine learning algorithms Random forests, Support vector machines, and hidden Markov models to classify reindeer behaviour into seven classes: grazing, browsing low from shrubs or browsing high from trees, inactivity, walking, trotting, and other behaviours. We implemented leave-one-subject-out cross-validation to assess generalizable results on new individuals. Our main results illustrated that hidden Markov models were able to classify collar-attached accelerometer data into all our pre-defined behaviours of reindeer with reasonable accuracy while Random forests and Support vector machines were biased towards dominant classes. Random forests using 5-s windows had the highest overall accuracy (85%), while hidden Markov models were able to best predict individual behaviours and handle rare behaviours such as trotting and browsing high. We conclude that hidden Markov models provide a useful tool to remotely monitor reindeer and potentially other large herbivore species behaviour. These methods will allow us to quantify fine-scale behavioural processes in relation to environmental events.
Research on copper production of the Bohai Kingdom in Northeast China
Authors: Li Chenyuan , Wu Song , Li Qiang , Song Yubin , Jia Ying , Li Yanxiang 
Published: September 2022

Abstract
The systematic investment and rearrangement of the unearthed artefacts of Longtoushan Royal Cemetery of the Bohai Kingdom have provided a bunch of new information for the archaeometallurgy research on non-ferrous metal production. We have synthesised the latest discoveries of several related mining/smelting sites and urban relics for making a direct approach to the chain of copper production in this research. SEM-EDS and p-XRF unveiled the distinction between copper and bronze artefacts. The yield gap between the scale of smelting and the number of artefacts was also discussed based on historical records. The evidence and detail of indigenous copper production could help the researcher comprehend the technology and material exchange and geopolitical relationship development of the Bohai Kingdom.
Seismic analysis, design, and retrofit of built-environments: a procedural review of current practices and case studies
Authors: Kim Ju-Hyung , Hessek Christopher J. , Kim Yail J. , Park Hong-Gun 
Published: September 2022

AbstractThis paper presents a synthesis of current practices in regard to the seismic analysis, design, and retrofit of built-environments. Background information on the behavior of existing buildings subjected to earthquake loadings is gathered and rehabilitation methodologies are elaborated. The first part of the review examines design standards and guidelines that are used in the structural engineering community. These documents are mandatory for the legal adoption of a model code by the governing jurisdiction where the building in question is to be located. The second part discusses retrofit procedures alongside specific provisions dominating the requirements and techniques appertaining to ground motions. The third part handles case studies emphasizing an upgrade of school buildings that are non-conforming to contemporary specifications and guidelines. For substantiating the performance of proposed methodologies, laboratory tests are conducted in conjunction with finite element analysis, which form the technical foundation of site implementations.
Aging Impairs Adaptive Unfolded Protein Response and Drives Beta Cell Dedifferentiation in Humans
Authors: Song Jiaxi , Ni Qicheng , Sun Jiajun , Xie Jing , Liu Jianmin , Ning Guang , Wang Weiqing , Wang Qidi 
Published: September 2022

Abstract

Context
Diabetes is an age-related disease; however, the mechanism underlying senescent beta cell failure is still unknown.

Objective
The present study was designed to investigate whether and how the differentiated state was altered in senescent human beta cells by excluding the effects of impaired glucose tolerance.

Methods
We calculated the percentage of hormone-negative/chromogranin A–positive endocrine cells and evaluated the expressions of forkhead box O1 (FoxO1) and Urocortin 3 (UCN3) in islets from 31 nondiabetic individuals, divided into young (&lt;40 years), middle-aged (40-60 years) and elderly (&gt;60 years) groups. We also assessed adaptive unfolded protein response markers glucose-regulated protein 94 (GRP94), and spliced X-box binding protein 1 (XBP1s) in senescent beta cells and their possible contributions to maintaining beta cell identity and differentiation state.

Results
We found an almost 2-fold increase in the proportion of dedifferentiated cells in elderly and middle-aged groups compared with the young group (3.1 ± 1.0% and 3.0 ± 0.9% vs 1.7 ± 0.5%, P &lt; .001). This was accompanied by inactivation of FoxO1 and loss of UCN3 expression in senescent human beta cells. In addition, we demonstrated that the expression levels of adaptive unfolded protein response (UPR) components GRP94 and XBP1s declined with age. In vitro data showed knockdown GRP94 in Min6-triggered cells to dedifferentiate and acquire progenitor features, while restored GRP94 levels in H2O2-induced senescent Min6 cells rescued beta cell identity.

Conclusion
Our finding highlights that the failure to establish proper adaptive UPR in senescent human beta cells shifts their differentiated states, possibly representing a crucial step in the pathogenesis of age-related beta cell failure.
Idiopathic Hirsutism and Metabolic Status: A Population-based Prospective Cohort Study
Authors: Mahmoudieh Leila , Amiri Mina , Rahmati Maryam , Habibi Moeini Ali Siamak , Sarvghadi Farzaneh , Azizi Fereidoun , Ramezani Tehrani Fahimeh 
Published: September 2022

Abstract

Background
A limited number of studies have investigated the impact of idiopathic hirsutism (IH) on cardiometabolic parameters with contradictory and inconclusive results. This study aimed to explore the effect of IH on metabolic outcomes.

Method
In this population-based prospective study, 334 women with IH and 1226 women as healthy controls were selected from Tehran Lipid and Glucose Study. The generalized estimation equations method was applied to investigate the secular longitudinal trends of metabolic indices, including fasting blood sugar (FBS), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL), non-HDL, triglyceride (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and waist circumference (WC) in both groups. Unadjusted and adjusted Cox regression models were applied to assess the hazard ratios (HR) and 95% CIs for the association between IH and metabolic disorders. Potential confounding factors such as age, body mass index, smoking, physical activity, history of hypertension (HTN), and family history of diabetes were included in the adjusted model.

Results
This study showed that compared with healthy controls, women with IH had lower SHBG and higher total testosterone (median [interquartile ratio; IQR]: 0.37 [0.16-0.70] vs 0.33 [0.14-0.58]; P = 0.01), free androgen index (median [IQR]: 0.85 [0.38-1.54] vs 0.54 [0.26-0.97]; P = 0.001), androstenedione (median [IQR]: 1.60 [1.00-2.25] vs 1.10 [0.90-1.70]; P = 0.001), and dehydroepiandrosterone sulfate (median [IQR]: 168.5 [91.1-227.8] vs 125.2 [66.3-181]; P = 0.001). Over time, mean changes of FBS, HDL-C, LDL-C, non-HDL-C, TG, SBP, DBP, and WC were not significantly different in women with IH, compared with healthy controls. According to the unadjusted Cox regression model, except for type 2 diabetes mellitus (T2DM) (HR [95% CI]: 1.45 [1.00-2.11]) P = 0.05; there was no statistically significant difference in hazard of metabolic disorders (ie, HTN, pre-HTN, pre-T2DM, and metabolic syndrome) in IH, compared with healthy controls. Besides, the adjusted Cox regression model showed no significant differences in the hazard of these outcomes.

Conclusion
This study showed no significant difference in overtime mean changes of metabolic risk factors and cardiometabolic outcomes in women with IH, compared with the healthy control group, except marginally significant difference on T2DM, which disappeared after further adjustment for potential confounders. Accordingly, routine screening of women for these metabolic outcomes should not recommend.
Circulating Plasma Concentrations of ACE2 in Primary Aldosteronism and Cardiovascular Outcomes
Authors: Wu Vin-Cent , Peng Kang-Yung , Hu Ya-Hui , Chang Chin-Chen , Chan Chieh-Kai , Lai Tai-Shuan , Lin Yen-Hung , Wang Shuo-Meng , Lu Ching-Chu , Liu Yu-Chun , Tsai Yao-Chou , Chueh Jeff S 
Published: September 2022

Abstract

Context
The plasma concentrations of angiotensin-converting enzyme 2 (pACE2) has been independently associated with cardiovascular diseases.

Objective
Higher pACE2 concentrations may be found in patients with primary aldosteronism (PA) and might lead to increased cardiovascular events.

Methods
Using an inception observational cohort, we examined pACE2 among 168 incident patients with PA. The expression of ACE2, serine protease 2 (TMPRSS2), and metalloprotease 17 (ADAM17) were assessed in peripheral blood mononuclear cells.

Results
Incident PA and essential hypertension (EH) patients had similarly elevated pACE2 (47.04 ± 22.06 vs 46.73 ± 21.06 ng/mL; P = .937). Age was negatively (β = −2.15; P = .033) and higher serum potassium level (β = 2.29; P = .024) was positively correlated with higher pACE2 in PA patients. Clinical complete hypertension remission after adrenalectomy (Primary Aldosteronism Surgery Outcome criteria) was achieved in 36 (50%) of 72 surgically treated unilateral PA (uPA) patients. At follow-up, pACE2 decreased in surgically treated patients who had (P &lt; .001) or had no (P = .006) hypertension remission, but the pACE2 attenuation was not statistically significant in uPA (P = .085) and bilateral PA (P = .409) administered with mineralocorticoid receptor antagonist (MRA). Persistently elevated pACE2 (&gt; 23 ng/mL) after targeted treatments was related to all-cause mortality and cardiovascular events among PA patients (hazard ratio = 8.8; P = .04); with a mean follow-up of 3.29 years. TMPRSS2 messenger RNA (mRNA) expression was higher in uPA (P = .018) and EH (P = .038) patients than in normotensive controls; it was also decreased after adrenalectomy (P &lt; .001).

Conclusion
PA and EH patients had elevated pACE2 and higher expression of TMPRSS2 mRNA compared to those of normotensive population. Persistently elevated pACE2 (&gt; 23 ng/mL) after targeted treatments was associated risk of mortality and incident cardiovascular events.
Risk factors for postoperative infectious complications after RIRS treatment of kidney and ureteral stones
Authors: Stachura Tomasz , Bąk Sebastian , Budzeń Kamil , Wesołowski Paweł , Gładysz Konrad , Marzęda Magdalena , Blicharz Agnieszka , Sygacz Oliwer 
Published: September 2022

Abstract
Introduction and aim of the study: Urolithiasis is a disease involving the formation of deposits in the lumen of the urinary tract. The continued development of minimally invasive treatment methods allows for more effective treatment with greater operator comfort and less risk to the patient. It has been concluded that retrograde intrarenal surgery (RIRS) is superior to other therapeutic methods in many respects. The aim of this study is to review the available studies and publications and to identify potential complications following treatment of kidney and ureteral stones by RIRS, with a particular focus on infectious complications and their risk factors.

Method and materials: We reviewed the literature available on PubMed and Google Scholar, using the words 'urolithiasis'; 'urolithiasis treatment'; 'retrograde intrarenal surgery'; 'infectious complications of retrograde intrarenal surgery'.

Results: Among the risk factors associated with infectious complications after RIRS, long duration of surgery, recent positive urine culture, urinary tract infections or antibiotic use, purulent urine, urinary nitrites, obstructed access through the ureter, struvite stones, co-morbidities play a special role.

Conclusions: Among the complications of surgical treatment of nephrolithiasis and ureteral stones by RIRS, infectious complications are of particular concern. In view of the knowledge of their risk factors, preventive measures should include limiting the duration of surgery, possible antibiotic therapy and considering the use of a larger diameter UAS. This is especially true for patients with abnormal urine results, struvite stones, a history of urinary tract infection or predisposing comorbidities.

Key words: Urolithiasis; Kidney Calculi; Retrograde Intrarenal Surgery; Urolithiasis infection;
Nearly degenerate two-color impulsive coherent Raman hyperspectral imaging
Authors: Smith David R. , Shivkumar Siddarth , Field Jeff , Wilson Jesse W. , Rigneault Hervé , Bartels Randy A. 
Published: September 2022

Impulsive stimulated Raman scattering (ISRS) is a robust technique for studying low frequency (<300 cm−1) Raman vibrational modes, but ISRS has faced difficulty in translation to an imaging modality. A primary challenge is the separation of the pump and probe pulses. Here we introduce and demonstrate a simple strategy for ISRS spectroscopy and hyperspectral imaging that uses complementary steep edge spectral filters to separate the probe beam detection from the pump and enables simple ISRS microscopy with a single-color ultrafast laser source. ISRS spectra are obtained that span from the fingerprint region down to <50 cm−1 vibrational modes. Hyperspectral imaging and polarization-dependent Raman spectra are also demonstrated.
Decontamination of Geobacillus Stearothermophilus using the Arca Aerosolized Hydrogen Peroxide decontamination system
Authors: Mead Loren Benjamin , Mathison Tanner , Osborne Garry , Richards Anne Marie 
Published: September 2022

Introduction
In response to the limited supply of personal protective equipment during the pandemic caused by SARS-CoV-2, recent studies demonstrate that gaseous H2O2 is an effective decontaminant of N95 filtering facepiece respirators to enable reuse of these items in a clinical setting. This paper evaluates the efficacy of the Arca Aerosolized Hydrogen Peroxide Decontamination System (Arca), a novel aerosolized H2O2 decontamination system, using biologic indicator testing.

Materials and methods
The Arca produces and circulates H2O2 aerosol inside of a sealed stainless steel chamber. The Arca’s decontamination efficacy was evaluated in 8 decontamination trials with 2 H2O2 concentrations (3% and 12%) and 4 decontamination cycle durations (45, 60, 90, and 120 minutes). Efficacy was evaluated by testing: 1) the concentration in parts per million (ppm) of H2O2 produced inside the chamber and the concentration in ppm of H2O2 vented from the chamber, and 2) the decontamination of Mesa Biologic Indicator filter strips (BI) inoculated with Geobacillus Stearothermophilus. Control tests were conducted by submerging BI strips in 3mL of 3% and 12% H2O2 for 120 minutes (negative controls) and by not exposing one BI strip to H2O2 (positive control).

Results
Greater than 5000 ppm of H2O2 was detected on the concentration strips inside the chamber for each of the eight decontamination trials. No vented H2O2 was detected on the external concentration strips after any decontamination trial. No growth was observed for any of the negative controls after seven days. The positive control was positive for growth.

Conclusion
The Arca Aerosolized Hydrogen Peroxide Decontamination System is effective at decontaminating bacterial G. Stearothermophilus at a cycle time of 45 minutes utilizing 6mL of 3% H2O2 solution.
Enflicoxib for canine osteoarthritis: A randomized, blind, multicentre, non-inferiority clinical trial compared to mavacoxib
Authors: Salichs Marta , Badiella Llorenç , Sarasola Patxi , Homedes Josep 
Published: September 2022

Background
This prospective, multisite, blinded, randomized, non-inferiority clinical study aimed to confirm the efficacy and safety of enflicoxib in the treatment of pain and inflammation associated with canine osteoarthritis. A total of 180 dogs were randomized to receive enflicoxib (n = 78), mavacoxib (n = 80) or placebo (n = 22). Dogs underwent veterinary assessments from day 0 to day 42 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). The primary efficacy endpoint was the overall CSS from day 0 to day 42.

Results
The overall CSS expressed as area under the curve demonstrated non-inferiority of enflicoxib compared to mavacoxib, and both showed superiority over placebo. At the end of the study, average CSS, and the percentage of CSS responders for enflicoxib (3.64 and 74%) and mavacoxib (4.49 and 68%), was superior to placebo (7.15 and 29%). A faster onset of action was observed for enflicoxib as superiority over placebo was evidenced from the first efficacy assessment (day 7) onwards for both parameters, whereas mavacoxib was only significantly different from day 14 onwards. According to the owner assessment, the percentage of CBPI responders was 90%, 79%, and 43% for dogs treated with enflicoxib, mavacoxib and placebo, respectively, and superiority over placebo was demonstrated for both active treatments. In all secondary parameters, non-inferiority of enflicoxib versus mavacoxib was confirmed. The dog’s quality of life improved in all groups, but only enflicoxib showed superiority versus placebo. When assessing severely affected dogs only, results were similar, thus confirming the efficacy of enflicoxib in all stages of canine OA. There were no differences between groups in the frequency of adverse events, which were most frequently mild affecting the gastrointestinal tract and recovered without treatment.

Conclusions
Enflicoxib is efficacious and safe for the treatment of pain and inflammation in any stage of canine osteoarthritis with a faster onset of action compared to mavacoxib.