bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of solar power plants with hybrid systems
Authors: Koko J , Riza A , Mohamad Khadik U K 
Published: May 2021

Abstract
The design of hybrid power plants aims to provide alternative solutions to the community in the event of a power outage. This solar power generation system utilizes solar panels that have the function of converting sunlight energy into direct electrical energy which is used as the main source in battery charging. In a hybrid solar power plant system that is made equipped with a logger system that stores data about temperature, current, voltage on the solar panel, battery percentage, output power at the load, charging source and the power used at the load. From the results of the design and testing of the hybrid charging system, the main power source of the solar panel, if the battery power is less than 40%, the charging system moves to PLN (the state electricity company) and when the battery power is above 50%, the charging from the PLN will be turned off, at Auto Transfer Switch (ATS) system will be active if the power from the PLN goes out, the relay will move the PLN power to battery power for 3 seconds due to the start of the inverter, if the PLN power is on, the power from the inverter will move to PLN directly with no pause.
OCTID: a one-class learning-based Python package for tumor image detection
Authors: Wang Yanan , Yang Litao , Webb Geoffrey I , Ge Zongyuan , Song Jiangning 
Published: May 2021

Abstract

Motivation
Tumor tile selection is a necessary prerequisite in patch-based cancer whole slide image analysis, which is labor-intensive and requires expertise. Whole slides are annotated as tumor or tumor free, but tiles within a tumor slide are not. As all tiles within a tumor free slide are tumor free, these can be used to capture tumor-free patterns using the one-class learning strategy.

Results
We present a Python package, termed OCTID, which combines a pretrained convolutional neural network (CNN) model, Uniform Manifold Approximation and Projection (UMAP) and one-class support vector machine to achieve accurate tumor tile classification using a training set of tumor free tiles. Benchmarking experiments on four H&E image datasets achieved remarkable performance in terms of F1-score (0.90 ± 0.06), Matthews correlation coefficient (0.93 ± 0.05) and accuracy (0.94 ± 0.03).

Availability and implementation
Detailed information can be found in the Supplementary File.

Supplementary information
Supplementary data are available at Bioinformatics online.
Dynamic Network Analysis Demonstrates the Formation of Stable Functional Networks During Rule Learning
Authors: Morin Thomas M , Chang Allen E , Ma Weida , McGuire Joseph T , Stern Chantal E 
Published: May 2021

AbstractVariations in the functional connectivity of large-scale cortical brain networks may explain individual differences in learning ability. We used a dynamic network analysis of fMRI data to identify changes in functional brain networks that are associated with context-dependent rule learning. During fMRI scanning, naïve subjects performed a cognitive task designed to test their ability to learn context-dependent rules. Notably, subjects were given minimal instructions about the task prior to scanning. We identified several key network characteristics associated with fast and accurate rule learning. First, consistent with the formation of stable functional networks, a dynamic community detection analysis revealed regionally specific reductions in flexible switching between different functional communities in successful learners. Second, successful rule learners showed decreased centrality of ventral attention regions and increased assortative mixing of cognitive control regions as the rules were learned. Finally, successful subjects showed greater decoupling of default and attention communities throughout the entire task, whereas ventral attention and cognitive control regions became more connected during learning. Overall, the results support a framework by which a stable ventral attention community and more flexible cognitive control community support sustained attention and the formation of rule representations in successful learners.
The Incubation Period Distribution of Coronavirus Disease 2019: A Systematic Review and Meta-analysis
Authors: Xin Hualei , Wong Jessica Y , Murphy Caitriona , Yeung Amy , Taslim Ali Sheikh , Wu Peng , Cowling Benjamin J 
Published: May 2021

Abstract
Incubation period is an important parameter to inform quarantine period and to study transmission dynamics of infectious diseases. We conducted a systematic review and meta-analysis on published estimates of the incubation period distribution of coronavirus disease 2019, and showed that the pooled median of the point estimates of the mean, median and 95th percentile for incubation period are 6.3 days (range, 1.8–11.9 days), 5.4 days (range, 2.0–17.9 days), and 13.1 days (range, 3.2–17.8 days), respectively. Estimates of the mean and 95th percentile of the incubation period distribution were considerably shorter before the epidemic peak in China compared to after the peak, and variation was also noticed for different choices of methodological approach in estimation. Our findings implied that corrections may be needed before directly applying estimates of incubation period into control of or further studies on emerging infectious diseases.
NIAID ClinRegs—a Public Database of Country Clinical Research Regulatory and Ethics Requirements: Design and Utilization Analysis
Authors: Kagan Jonathan , Goodman Geoffrey N , Oh Rachel , Whitworth Diane , Gladden Darcie , Graves Gail , Nguyen Antonia , Shrestha Orish , Burge Gerald , Smolskis Mary , Andrews Janet , Cramer Brian , Lane H Clifford 
Published: May 2021

Abstract
Regulatory compliance is challenging for multinational clinical trials. Conflicts between country requirements impedes research and slows the approval of medicines, leading the pharmaceutical industry to devote significant resources to this area. Many academic centers and nonprofits cannot support industry-level investment and are vulnerable to noncompliance. To address an insufficiency in public access to this information, the National Institute of Allergy and Infectious Diseases developed ClinRegs—a public access database of clinical research regulations. This report describes ClinRegs’ features, maintenance, and usage. From September 2019 through August 2020, ClinRegs had 68 504 users, 60% from outside the United States, demonstrating the demand for accessible, reliable, country-specific regulatory information. Tools such as ClinRegs can help increase regulatory compliance and free up resources for research. We encourage our partner agencies and biomedical research industries to promote greater regulatory knowledge sharing and harmonization for the betterment of clinical research and improved public health.
KMDATA: a curated database of reconstructed individual patient-level data from 153 oncology clinical trials
Authors: Fell Geoffrey , Redd Robert A , Vanderbeek Alyssa M , Rahman Rifaquat , Louv Bill , McDunn Jon , Arfè Andrea , Alexander Brian M , Ventz Steffen , Trippa Lorenzo 
Published: May 2021

AbstractWe created a database of reconstructed patient-level data from published clinical trials that includes multiple time-to-event outcomes such as overall survival and progression-free survival. Outcomes were extracted from Kaplan–Meier (KM) curves reported in 153 oncology Phase III clinical trial publications identified through a PubMed search of clinical trials in breast, lung, prostate and colorectal cancer, published between 2014 and 2016. For each trial that met our search criteria, we curated study-level information and digitized all reported KM curves with the software Digitizelt. We then used the digitized KM survival curves to estimate (possibly censored) patient-level time-to-event outcomes. Collections of time-to-event datasets from completed trials can be used to support the choice of appropriate trial designs for future clinical studies. Patient-level data allow investigators to tailor clinical trial designs to diseases and classes of treatments. Patient-level data also allow investigators to estimate the operating characteristics (e.g. power and type I error rate) of candidate statistical designs and methods.Database URL: https://10.6084/m9.figshare.14642247.v1
DOP53 Pregnancy outcomes in the ozanimod clinical development program in relapsing multiple sclerosis, Ulcerative Colitis, and Crohn’s Disease
Authors: Dubinsky M C , Mahadevan U , Charles L , Afsari S , Henry A , Comi G , Selmaj K , van der Woude C J 
Published: May 2021

Abstract

Background
Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, has demonstrated efficacy in patients with relapsing multiple sclerosis (rMS) and ulcerative colitis (UC), and is being studied in Crohn’s disease (CD). S1P1-3 receptors are involved in vascular formation during embryogenesis. Within studies in the ozanimod clinical development program, female participants of childbearing potential were required to use effective contraception while receiving and up to 3 months after discontinuing ozanimod; treatment discontinuation was required if pregnancy was confirmed. Here we review pregnancy outcomes data with ozanimod use in rMS, UC, and CD.

Methods
All pregnancies, including participant and partner pregnancies, in the ozanimod clinical development program with an initial diagnosis prior to a cut-off date of September 30, 2020 were assessed for pregnancy outcomes.

Results
At cut-off, safety data on 4131 participants were available. A total of 83 pregnancies were reported in the safety database of participants treated with ozanimod or their partners (Table). All pregnancy exposures occurred during the first trimester. Of the 60 pregnancies in ozanimod clinical trials, 9 were reported in patients with UC, and 3 in patients with CD. Participants discontinued study medication promptly except for those who elected pregnancy termination and did not discontinue study medication. Among all pregnancies in the ozanimod clinical development program, the incidence of spontaneous abortion in clinical trial participants was 15%; the rate in the general population is between 12% and 22%. The rate of preterm birth was 10.7% of live births; as reference, the global population estimate is 10.6% and the European estimate is 8.7%. No teratogenicity was observed. Outcomes in patients with UC included 2 live births that resulted in 2 full-term healthy newborns, 2 ongoing pregnancies, 2 spontaneous early losses, and 3 elective terminations.

Conclusion
While pregnancy should be avoided in patients on and 3 months after stopping ozanimod and clinical experience with ozanimod during pregnancy is limited, there has been no increased event of foetal abnormalities or adverse pregnancy outcomes seen with ozanimod exposure in early pregnancy.
DOP55 Histopathological features at diagnosis to predict long-term disease course of Crohn’s Disease
Authors: Rezazadeh Ardabili A , Goudkade D , Wintjens D S J , Romberg-Camps M J L , Winkens B , Pierik M J , Grabsch H I , Jonkers D M A E 
Published: May 2021

Abstract

Background
Crohn’s disease (CD) is characterized by a heterogeneous disease course and treatment response. There is a clinical need to identify CD patients at diagnosis who are at risk for developing a severe disease course. Patient stratification using state-of-the-art clinical, serological or genetic markers does not predict disease course sufficiently to facilitate clinical decision making. The current study aimed to investigate the additive predictive value of histopathological features at diagnosis to discriminate between patients with a long-term mild and severe disease course.

Methods
Diagnostic biopsies from treatment-naïve CD patients with mild or severe disease courses in the first 10 years after diagnosis (i.e. based on the number of quarterly flares) were reviewed by two senior gastrointestinal pathologists after developing a standardized form comprising 15 histopathological features related to acute and chronic inflammation. Multivariable logistic regression models were built to identify predictive features and compute receiver operating characteristics (ROC) curves. Model 1 included clinically relevant baseline characteristics (Montreal classification, smoking status and gender). Next, histopathological were added by applying two different model-building strategies (forward selection and purposeful selection algorithm)(Model 2). Prediction models were internally validated using bootstrapping to obtain optimism-corrected performance estimates.

Results
In total, 817 biopsies from 137 CD patients (64 mild disease course, 73 severe disease course) were included. Based on clinical baseline characteristics alone, disease course could only be moderately predicted (Model 1 Area under ROC (AUROC): 0.738 (optimism 0.018), 95%CI 0.65–0.83, sensitivity 83.6%, specificity 53.1%). When adding histopathological features, in colonic, but not ileal, biopsies a combination of (1) basal plasmacytosis, (2) severe lymphocyte and plasma cell infiltration in the lamina propria, (3) Paneth cell metaplasia and (4) absence of ulcers were identified and resulted in significantly better prediction of a severe disease course (Model 2 AUROC: 0.883 (optimism 0.033), 95%CI 0.82–0.94, sensitivity 80.4%, specificity 84.2%, model 2 vs. model 1 AUROC p = 0.001)[Figure 1].

Conclusion
In this first study investigating the additive predictive value of multiple histopathological features in biopsies at CD diagnosis, we found that certain features of chronic inflammation in colonic biopsies contributed to prediction of a severe disease course, thereby presenting a novel approach to improve stratification and facilitate clinical decision making.
DOP64 Endoscopically injected allogeneic mesenchymal stromal cells alter the mucosal immune cell compartment in patients with ulcerative proctitis
Authors: Ouboter L , Barnhoorn M , Plug L , van Pel M , Zwaginga J J , Roelen D , Pascutti F , Koning F , Hawinkels L , Verspaget H , van der Meulen - de Jong A 
Published: May 2021

Abstract

Background
Local mesenchymal stromal cell (MSC)-therapy is approved for the treatment of Crohn’s disease-associated perianal fistulas. However, little is known about the working mechanism of local MSC-therapy. For the first time we evaluated engraftment and immunoregulatory effects of local MSC-therapy in patients with refractory proctitis. To do so, we analyzed biopsies and serum from patients with ulcerative proctitis before and after treatment with endoscopically injected MSCs in a phase IIa clinical trial (EudraCT number 2017-003524-75).

Methods
Thirteen therapy-refractory ulcerative proctitis patients were endoscopically injected bone marrow-derived allogeneic MSCs from healthy donors. Clinical efficacy was evaluated by the endoscopic and full Mayo score. Engraftment of the MSCs was investigated using fluorescence in-situ hybridization (FISH) of sex chromosomes on post-treatment biopsies. The presence of anti-HLA-antibodies against the MSC-donor was determined in the serum. Changes in immune cell subsets were evaluated using cytometry-by-time-of-flight (CyTOF) analysis.

Results
Thirteen patients with an endoscopic Mayo score of 2 (n=3) or 3 (n=10) of the rectum were treated with local MSC-therapy. Although complete remission was not achieved, full Mayo score was improved at week 6 (median 8 [IQR 6–10]) compared to baseline (median 11 [IQR 9.5–12]) (p=0.001). Preliminary data using FISH on the Y-chromosome, indicated the presence of MSCs in the rectum biopsies of female patients treated with male donor derived-MSCs at week 6. At baseline, HLA-antibodies were present in four patients. Six weeks after local injection of the MSCs, two out of thirteen patients developed new class I and II HLA-antibodies against the MSCs. Interestingly, in two patients pre-existing HLA-antibodies showed increased/boosted levels after local MSC-therapy, while one additionally developed new HLA-antibodies. CyTOF analysis of inflamed rectal biopsies 6 weeks after MSC treatment revealed significantly increased frequencies of several myeloid subsets (i.e. CD11b+CD14+CCR7+/-CD127+CD25+HLADR+ and CD14+HLA-DR-CD123-CCR7+) and a subset of CD4+ memory T cells with a more exhausted/regulated phenotype (PD-1+TIGIT+CD69+CD38+CD69).

Conclusion
Local MSC-therapy in patients with refractory proctitis changed the rectal immune profile characterised by a significant increase in a subset of effector memory CD4+ cells and several myeloid subsets, which might be associated with immune modulation. These results provide the basis for future studies on the mechanism of action of MSCs on rectal mucosa. New anti-HLA class antibodies developed in 2/13 patients after local administration. Whether these latter results have consequences for MSC-donor selection deserves further study.
OP01 Comparison of fecal transplantation, fecal transplantation with the novel UC diet or the UC diet alone for Refractory Mild to Moderate Active Ulcerative Colitis: The CRAFT UC randomized controlled trial
Authors: Levine A , Scaldaferri F , Sarbagili Shabat C , Zittan E , Hirsch A , Mentella M C , Musca T , Cohen N A , Ron Y , Fliss Isakov N , Pfeffer J , Yaakov M , Fanali C , Turchini L , Masucci L , Quaranta G , Anastasia G , Weinberger A , Kopylov U , Maharshak N 
Published: May 2021

Abstract

Background
We evaluated if integration of novel diets for donors and patients in addition to fecal transplantation (FT) could increase FT remission in refractory ulcerative colitis (UC) or have an independent effect on remission. We developed a novel diet specifically designed for the dysbiosis of UC and to decrease factors that impair goblet cells or mucous production.

Methods
This was a blinded randomized controlled pilot trial in adults with UC, defined by a simple clinical colitis activity index (SCCAI) of ≥5 and &lt; 11 and endoscopic Mayo score 2–3, refractory to medication. Group 1 received free diet and standard FT by colonoscopy on day 1and rectal enemas from a single donor on days 2 and 14 without dietary conditioning of the donor. Group 2: FT as above but with dietary pre-conditioning of the donor for 14 days and a diet (UC Diet- UCD) for the patients after FT. Group 3 received the UC Diet alone without FT. Patients underwent a repeat endoscopy at week 8. The primary endpoint was clinical steroid free remission, defined as SCCAI &lt;3, at week 8.

Results
Fifty-one of the 96 planned patients were enrolled. The mean age was 40.4 ±12.5 years, 28/51(54.9%) had failed a biologic, 15/40 (29.4%) were on steroids at enrolment. Remission week 8 in Group 1 was 2/17(11.8%), Group 2 was 4/19 (21.1%), and 6/15 (40%) Group 3 (NS). Endoscopic remission was present in Group 1: 2/17(12%), Group 2: 3/19(16%) and 4/15 (27%) Group 3. Mucosal healing (Mayo 0) was achieved only in Group 3 (3/15, 20%) vs. 0/36 patients receiving FT (P=0.022). Exacerbation of disease occurred in 3/17 (17.6%) Group1, 4/19 (21.1%) Group 2, and 1/15 (6.7%) Group 3 (NS). The study was stopped for futility by a safety monitoring board.

Conclusion
Fecal transplantation was not effective in this UC cohort. A UC Diet alone appeared to achieve higher clinical remission (40%) and mucosal healing than single donor FT with or without diet in mild to moderate UC failing medical therapy. This diet should be investigated further in a RCT specifically designed for the UCD. This study was supported by an ECCO Pioneer grant
OP09 Patient reported outcomes reflect histologic disease activity in patients with Ulcerative Colitis: Interim analysis of the APOLLO study
Authors: Verstockt B , Jorissen C , Hoefkens E , Lembrechts N , Pouillon L , Bossuyt P 
Published: May 2021

Abstract

Background
Treating beyond endoscopic remission, aiming for histological remission, has shown to reduce relapse and hospitalization rates in patients with ulcerative colitis (UC). However, very little is known on how histological remission associates with patient reported outcomes (PROMs).

Methods
PROMs (Simple clinical colitis activity index [SCCAI], IBD disk and Visual Analogue Scales [VAS]) were prospectively collected through a digital questionnaire in all patients with UC undergoing colonoscopy between July 21st 2020-Jan 21st 2021. Mayo endoscopic sub score and UCEIS were determined, as well as the Nancy histologic index (NHI) of the most affected area. Endoscopic remission was defined as Mayo endoscopic sub score 0 and UCEIS 0; histologic remission as NHI 0, absence of active inflammation as NHI ≤ 1. PRO2 remission was defined as stool frequency ≤ 1 (absolute stool frequency ≤ 3 OR 1–2 stools more than usual) and rectal bleeding score of 0.

Results
Fifty-six paired assessments were collected in 48 unique patients (Table 1), with a histologic, endoscopic and PRO-2 remission rate of 23.2%, 28.6% and 38.2% respectively. Patients with histologic remission or absence of histologic inflammation had a significantly lower overall IBD disability (p=0.007, p=0.003) and disease activity score (p=0.003, p&lt;0.001), as compared to patients without. In line, NHI correlated with the overall IBD disk (r=0.40, p=0.002) and SCCAI score (r=0.50, p&lt;0.001). Many individual components of both scores (abdominal pain, arthralgia, impact on education and work/interpersonal interactions/sexual function, regulation of defecation, blood loss, general wellbeing, joint pain, numbers of stools during night/day, urgency) differed significantly between patients with and without histologic remission. VAS scores assessing general wellbeing (r=0.33, p=0.01), impact on daily activities (r=0.41, p=0.002), UC-related symptoms (r=0.42, p=0.001) and worries (r=0.40, p=0.002) correlated with histology. Quartile analysis of the overall IBD disk and SCCAI scores confirmed the highest likelihood for histologic remission in patients with the lowest scores (Q1-Q2 vs Q3-Q4 39.3% vs 7.1%, p=0.01; 40.0% vs 9.7%, p=0.01) (Figure 1). Nevertheless, the overall accuracy of the IBD disk (0.75) or SCCAI score (0.76) for histologic remission is lower (p&lt;0.05) than the accuracy of the Mayo endoscopic (0.90) or UCEIS (0.90) score.
Table 1: Baseline features

Abstract OP09 – Figure 1: Quartile analysis

Conclusion
In patients with UC, PROMs for disability and clinical disease activity reflect histologic disease activity and should therefore be further explored in (trial) endpoint discussions. However, they cannot fully replace endoscopic and histologic findings, and should be considered complementary.