bluuebunny/crossref_metadata_2025_split huggingface dataset:
REAL WORLD EFFECTIVENESS AND SAFETY OF OZANIMOD: INITIAL RESULTS FROM A LARGE TERTIARY CENTER
Authors: Cohen Nathaniel , Choden Tenzin , Choi David , Cleveland Noa , Cohen Russell , Dalal Sushila , Sakuraba Atsushi , Hanan Ira , Rubin David 
Published: January 2022

Abstract

BACKGROUND
In May 2021 the United Stated Food and Drug Administration (FDA) approved the use of ozanimod for moderate to severe ulcerative colitis (UC) based on the results of the pivotal phase 3 TRUE NORTH trials. We present the first report of real world data describing the use of ozanimod in clinical practice.

METHODS
This prospective, observational cohort study includes consecutive patients with active UC who initiated ozanimod at our center following FDA approval. We collected demographic, clinical, and laboratory data. Clinical disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI). Clinical response was defined as a decrease in ≥3 points in SCCAI from baseline, and clinical remission was defined as an SCCAI score of ≤ 2. Adverse events were extracted from the electronic medical records (EMR) and regular clinical pharmacist follow up.

RESULTS
18 patients have initiated ozanimod therapy at our center. We observed 15 patients with UC, 1 patient with indeterminate colitis (IC), 1 patient with Crohn’s colitis, and 1 patient with lymphocytic colitis. All patients were included in the safety analysis and only patients with UC or IC were included in the effectiveness analysis. The mean age was 44.7 ± 18.5 with a mean age at disease duration of 9.6 ± 10.4. Ten (62%) patients were male, most patients 11 (69) had left sided colitis; 12 (75%) had previous biologic exposure. Additional demographics are described in Table 1. At week 4, follow up was available for 11 patients. Among these, 7 (64%) patients demonstrated clinical response, 2 (18%) were in clinical remission, and 1 patient achieved corticosteroid (CS) free remission. At week 8, follow up data was available for 7 patients; 3 (43%) patients had a clinical response and 1 (14%) patient achieved CS free remission (Figure 1A). 7 patients had complete blood counts at weeks 0 and 4, and all of these patients had a reduction in absolute lymphocyte counts (mean ± SD 1.46±0.47 109 cells/liter) (Figure 1B). There were 5 adverse events during the follow up period, none of which required treatment cessation. 1 patient had self-limited gastroenteritis, 1 patient had transient fatigue and another transient nausea. 1 patient developed mild liver enzyme derangement. 1 patient had non-specific chest pain and therapy was paused for a day until investigations returned negative.

CONCLUSION
This is the first real world data from a relatively treatment refractory cohort of UC patients and shows promising effectiveness and safety of ozanimod. Longer follow-up in larger patient cohorts is required to assess ozanimod’s role in clinical practice.
SUCCESSFUL CLEARANCE OF CYTOMEGALOVIRUS COLITIS IN ACUTE SEVERE ULCERATIVE COLITIS DURING INDUCTION OF OZANIMOD
Authors: Mohamed Rana , Kern Cody , Fein Aaron , Barrett Terrence , Perry Courtney 
Published: January 2022

Abstract

INTRODUCTION
Cytomegalovirus (CMV) colitis, commonly observed in patients with acute severe ulcerative colitis (UC), increases the risk for colectomy and treatment resistance. Unfortunately, corticosteroids and immunomodulators increase CMV reactivation and infection. The use of certain biologics such as anti-TNF mAb increase the risk for CMV colitis, while experience with newer biologics is limited leaving clinicians with few validated options. Ozanimod, an oral sphingosine-1-phosphate receptor modulator, was recently approved for induction and maintenance therapy for UC. Experience with ozanimod in the setting of UC complicated by CMV infection has not been reported to this date. We report here on a severe UC patient with tissue proven CMV ulceration that cleared the viral infection during ozanimod induction.

CASE REPORT
A 21-year-old male with UC treated with tofacitinib presented with five days of diffuse abdominal pain and 10-12 episodes of bloody diarrhea per day with CRP 341mg/L (&lt;8.0mg/L) and calprotectin &gt;3000μg/g (&lt;49μg/g). Computed topography of the abdomen and pelvis showed diffuse wall thickening and mucosal enhancement throughout the entire colon and rectum. He was started on methylprednisolone 20mg TID for acute severe UC. He previously failed infliximab, adalimumab, ustekinumab, and vedolizumab. Colonoscopy showed pancolitis (Mayo score 3) with deep ulceration in the cecum. Random colon biopsies were consistent with active colitis with an area of CMV infection in an area of cecal ulceration (Figure 1). Serum CMV Quantitative PCR was 410IU/ml (normal &lt;50IU/ml). The patient refused colectomy and was started on IV ganciclovir 5mg/kg q12h while transitioning to prednisone 40mg/day. Three weeks after initial presentation and eleven days after starting ganciclovir, the patient began ozanimod. He remained on ganciclovir for three weeks then transitioned to oral valganciclovir 900mg BID. The patient’s symptoms improved, CRP normalized, and calprotectin levels dropped (1200μg/g). Repeat colonoscopy performed eighteen days after ozanimod initiation revealed moderately-improved pancolitis (Mayo 2) with multiple healing cecal ulcers. Analysis of cecal ulceration IHC and peripheral blood PCR indicated clearing of the infection from the colon (Figure 2).

DISCUSSION
Cytomegalovirus colitis remains a common complication in severe UC, while avoidance of colectomy with viral clearance remains a challenge. Ozanimod and ganciclovir were chosen by this patient after refusing surgical resection. The improvement in clinical biomarkers of colitis and viral clearance suggest that ozanimod given with ganciclovir may be an exciting rescue therapy in these patients. Future studies will be needed to ascertain the rates of ozanimod response and CMV clearance in a larger patient cohort.
Preliminary Evidence on the Association of Complementary and Integrative Health Care Program Participation and Medical Cost in Veterans
Authors: Haun Jolie N , Paykel Jacquelyn , Fowler Christopher A , Lapcevic William A , Panaite Vanessa , Alman Amy C , Melillo Christine , Venkatachalam Hari H , French Dustin D 
Published: January 2022

ABSTRACT

Introduction
Transforming Health and Resilience through Integration of Values-based Experiences (THRIVE) is a complimentary and integrative health program. THRIVE is delivered through shared medical appointments where participants engage in provider-led education and group discussion on wellness-related topics. THRIVE has been associated with improved patient-reported outcomes in a female veteran cohort. This quality improvement study evaluated the association between THRIVE participation and Veterans Health Administration (VHA) healthcare costs across a 1 year period.

Materials and Methods
A cohort study design (n = 184) used VHA administrative data to estimate the cost difference between 1 year pre- and post-THRIVE participation. The 1 year post-cost of the THRIVE cohort was then compared to the 1 year cost of a quasi-experimental waitlist control group (n = 156). Data sources included VHA administrative and electronic health records.

Results
Patients were roughly 51 years old, were typically White/Caucasian, and had a service priority level representing catastrophic disability. The adjusted post-THRIVE cost was $26,291 [95% confidence interval (CI): $23,014–29,015]; $1,720 higher than the previous year’s cost but was not statistically significant (P = 0.289). However, a comparison between the THRIVE cohort and a group of waitlist THRIVE patients (n = 156) the intervention group on average was $8,108 more than the waitlist group (95% CI: $3,194–14,005; P &lt; 0.01).

Conclusions
In summary, data analysis of veterans’ annual healthcare cost trajectories were inconclusive. This preliminary study produced mixed results requiring more research with larger samples and randomized control trial methodology. Evidence of whether the THRIVE intervention can maintain cost effectiveness while maintaining its supported evidence of healthcare quality is needed.
Perceptions of Telemedicine and Costs Incurred by a Visit to a General Infectious Diseases Clinic: A Survey
Authors: Evers Emily C , Fritz Stephanie A , Colditz Graham A , Burnham Jason P 
Published: January 2022

Abstract

Background
The costs of attending in-person general infectious diseases clinics and preferences for visit type (telemedicine vs in-person) are not well known. We aimed to measure the time-related, monetary, social, and societal costs associated with travel to an in-person clinic visit and to assess patients’ preferences, questions, and concerns regarding telemedicine.

Methods
Patients (≥18 years, living ≥25 miles from clinic at time of clinic visit) were recruited for this survey study from the general infectious diseases (ID) clinic at Washington University from June 2019 to February 2020. We calculated time and money potentially saved by telemedicine, as well as carbon dioxide emissions, with the assistance of Google Maps (low/high estimates). We also determined patient preferences regarding telemedicine for ID care.

Results
Seventy-five patients completed the study. The round-trip mean travel distance was 227.2 ± 142.6 miles, mean travel time was 3.6 ± 2.0 hours to 4.5 ± 2.3 hours (low and high estimates from Google Maps), travel costs were $131.34 ± $82.27, and mean carbon dioxide emissions were 91.79 ± 57.60 kg. Fifty-eight patients (77.3%) said they would be willing to have a telemedicine visit in the future, and 30 (40.5%) said they would rather have had their visit the day the survey was completed as a telemedicine visit.

Conclusions
Telemedicine has the potential to significantly reduce patient costs, both monetary and time-related, and offers substantial environmental benefits, while being an acceptable method of care delivery to most patients at a general ID clinic.
COVID-19, policy change, and post-pandemic data governance: a case analysis of contact tracing applications in East Asia
Authors: Li Veronica Q T , Ma Liang , Wu Xun 
Published: January 2022

Abstract
In an era of digitalization, governments often turn to digital solutions for pressing policy issues, and the use of digital contact tracing and quarantine enforcement for COVID-19 is no exception. The long-term impacts of the digital solutions, however, cannot be taken for granted. The development and use of data tools for pandemic control, for example, may have potentially detrimental and irreversible impacts on data governance and, more broadly, society, in the long run. In this paper, we aim to explore the extent to which COVID-19 and digital contact tracing have led to policy change in data governance, if at all, and what the implications of such change would be for a post-COVID world. We compare the use of contact tracing and monitoring applications across mainland China, Hong Kong, and Singapore to illustrate both the enormous benefits and potential risks arising from the design of contact tracing applications and the involvement of stakeholders in the various stages of the policy cycle to combat the COVID-19 pandemic. We argue that, while COVID-19 has not changed the nature of issues, such as public trust in data governance, the increasing involvement of big tech in data policies, and data privacy risks, it has exacerbated those issues through the accelerated adoption of data technologies.
Predicting mechanical ventilation effects on six human tissue transcriptomes
Authors: Somekh Judith , Lotan Nir , Sussman Ehud , Yehuda Gur Arieh 
Published: January 2022

AbstractBackgroundMechanical ventilation (MV) is a lifesaving therapy used for patients with respiratory failure. Nevertheless, MV is associated with numerous complications and increased mortality. The aim of this study is to define the effects of MV on gene expression of direct and peripheral human tissues.MethodsClassification models were applied to Genotype-Tissue Expression Project (GTEx) gene expression data of six representative tissues– liver, adipose, skin, nerve-tibial, muscle and lung, for performance comparison and feature analysis. We utilized 18 prediction models using the Random Forest (RF), XGBoost (eXtreme Gradient Boosting) decision tree and ANN (Artificial Neural Network) methods to classify ventilation and non-ventilation samples and to compare their prediction performance for the six tissues. In the model comparison, the AUC (area under receiver operating curve), accuracy, precision, recall, and F1 score were used to evaluate the predictive performance of each model. We then conducted feature analysis per each tissue to detect MV marker genes followed by pathway enrichment analysis for these genes.ResultsXGBoost outperformed the other methods and predicted samples had undergone MV with an average accuracy for the six tissues of 0.951 and average AUC of 0.945. The feature analysis detected a combination of MV marker genes per each tested tissue, some common across several tissues. MV marker genes were mainly related to inflammation and fibrosis as well as cell development and movement regulation. The MV marker genes were significantly enriched in inflammatory and viral pathways.ConclusionThe XGBoost method demonstrated clear enhanced performance and feature analysis compared to the other models. XGBoost was helpful in detecting the tissue-specific marker genes for identifying transcriptomic changes related to MV. Our results show that MV is associated with reduced development and movement in the tissues and higher inflammation and injury not only in direct tissues such as the lungs but also in peripheral tissues and thus should be carefully considered before being implemented.
Epigenetic anti-cancer treatment with a stabilized carbocyclic Decitabine analogue
Authors: Traube Franziska R. , Brás Natércia F. , Roos Wynand P. , Sommermann Corinna C. , Diehl Tamara , Mayer Robert J. , Ofial Armin R. , Müller Markus , Zipse Hendrik , Carell Thomas 
Published: January 2022

Abstract5-Aza-2’-deoxycytidine (Decitabine, AzadC) is a nucleoside analogue, which is in clinical use to treat patients with myelodysplastic syndrome or acute myeloid leukemia. Its mode of action is unusual because the compound is one of the few drugs that act at the epigenetic level of the genetic code. AzadC is incorporated as an antimetabolite into the genome and creates covalent, inhibitory links to DNA methyltransferases (DNMTs) that methylate 2’-deoxycytidine (dC) to 5-methyl-dC (mdC). Consequently, AzadC treatment leads to a global loss of mdC, which presumably results in a reactivation of silenced genes, among them tumor suppressor and DNA damage response genes. Because AzadC suffers from severe instability, which limits its use in the clinic, a more sophisticated AzadC derivative would be highly valuable. Here, we report that a recently developed carbocyclic AzadC analogue (cAzadC) blocks DNMT1 in the AML cell line MOLM-13 as efficient as AzadC. Moreover, cAzadC has a surprisingly strong anti-proliferative effect and leads to a significantly higher number of double strand breaks compared to AzadC, while showing less off-target toxicity. These results show that cAzadC triggers more deleterious repair and apoptotic pathways in cancer cells than AzadC, which makes cAzadC a promising next generation epigenetic drug.
Mosquito odorant receptor sensitive to natural spatial repellents and inhibitory compounds
Authors: Xu Pingxi , Choo Young-Moo , An Sunny , Leal Gabriel M. , Leal Walter S. 
Published: January 2022

AbstractPreviously, we have identified an odorant receptor (OR) from the southern house mosquito Culex quinquefasciatus, CquiOR32, which responded to both odorants (agonists) and inhibitory compounds (antagonists). CquiOR32/CquiOrco-expressing oocytes responded to methyl salicylate and other odorants with inward (regular) currents but gave currents in the reverse direction when challenged with eucalyptol and other inhibitors. To determine whether hitherto unknown ORs show this intrareceptor inhibition, we have now examined two other receptors in the same cluster, CquiOR27 and CquiOR28. We cloned and tested four variants of CquiOR28, but none of the 250 compounds in our panel of odorants, including an Orco ligand candidate (OCL12), elicited inward or outward currents. By contrast, CquiOR27/CquiOrco-expressing oocytes gave robust, dose-dependent inward currents when challenged with γ-octalactone and other odorants. On the other hand, octylamine and other phenolic compounds elicited dose-dependent currents in the reverse direction. When stimulatory and inhibitory compounds were presented in binary mixtures, γ-octalactone-elicited inward currents were attenuated in a dose-dependent manner according to the concentration of octylamine. As part of our chemical ecology approach, we tested the repellency activity of the best ligands in the surface landing and feeding assay and a newly reported hand-in cage assay. Protection elicited by γ-octalactone did not differ significantly from that of DEET at the same dose. In the hand-in cage assay, a cream formulation of γ-octalactone showed 97.0 ± 1.3% protection, with 47.6 ± 8.3% and 1.4 ± 0.7% landings per trial in the hands covered with a control and γ-octalactone cream, respectively (N=8, p=0.0078, Wilcoxon matched-pairs signed-rank test).
Meta-analysis of Microbiome Association Networks Reveal Patterns of Dysbiosis in Diseased Microbiomes
Authors: Lam Tony J. , Ye Yuzhen 
Published: January 2022

AbstractThe human gut microbiome is composed of a diverse and dynamic population of microbial species which play key roles in modulating host health and physiology. While individual microbial species have been found to be associated with certain disease states, increasing evidence suggests that higher-order microbial interactions may have an equal or greater contribution to host fitness. To better understand microbial community dynamics, we utilize complex networks to study interactions through a meta-analysis of microbial association networks between healthy and disease gut microbiomes. Taking advantage of the large number of metagenomes derived from healthy individuals and patients with various diseases, together with recent advances in network inference that can deal with sparse compositional data, we inferred microbial association networks based on co-occurrence of gut microbial species and made the networks publicly available as a resource (github repository named GutNet). Through our meta-analysis of inferred networks, we were able to identify network-associated features that help stratify between healthy and disease states such as the differentiation of various bacterial phyla and enrichment of Proteobacteria interactions in diseased networks. Additionally, our findings show that the contributions of taxa in microbial associations are disproportionate to their abundances and that rarer taxa of microbial species play an integral part in shaping dynamics of microbial community interactions. Overall, this meta-analysis revealed valuable insights into microbial community dynamics between healthy and disease phenotypes.
Longitudinal Morphological and Functional Characterization of Human Heart Organoids Using Optical Coherence Tomography
Authors: Ming Yixuan , Hao Senyue , Xu Zhiyao , Goestenkors Anna , Lewis-Israeli Yonatan R. , Volmert Brett D. , Aguirre Aitor , Zhou Chao 
Published: January 2022

AbstractOrganoids play an increasingly important role asin vitromodels for studying organ development, disease mechanisms, and drug discovery. Organoids are self-organizing, organ-like three-dimensional (3D) cell cultures developing organ-specific cell types and functions. Recently, three groups independently developed self-assembling human heart organoids (hHOs) from human pluripotent stem cells (hPSCs). In this study, we utilized a customized spectral-domain optical coherence tomography (SD-OCT) system to characterize the growth of hHOs. Development of chamber structures and beating patterns of the hHOs were observed via OCT and calcium imaging. We demonstrated the capability of OCT to produce 3D images in a fast, label-free, and non-destructive manner. The hHOs formed cavities of various sizes, and complex interconnections were observed as early as on day 4 of differentiation. The hHOs models and the OCT imaging system showed promising insights as anin vitroplatform for investigating heart development and disease mechanisms.
ATLIGATOR: Editing protein interactions with an atlas-based approach
Authors: Kynast Josef Paul , Schwägerl Felix , Höcker Birte 
Published: January 2022

AbstractMotivationRecognition of specific molecules by proteins is a fundamental cellular mechanism and relevant for many applications. Being able to modify binding is a key interest and can be achieved by repurposing established interaction motifs. We were specifically interested in a methodology for the design of peptide binding modules. By leveraging interaction data from known protein structures, we plan to accelerate the design of novel protein or peptide binders.ResultsWe developed ATLIGATOR – a computational method to support the analysis and design of a protein’s interaction with a single side chain. Our program enables the building of interaction atlases based on structures from the PDB. From these atlases pocket definitions are extracted that can be searched for frequent interactions. These searches can reveal similarities in unrelated proteins as we show here for one example. Such frequent interactions can then be grafted onto a new protein scaffold as a starting point of the design process. The ATLIGATOR tool is made accessible through a python API as well as a CLI with python scripts.Availability and ImplementationSource code can be downloaded at github (https://www.github.com/Hoecker-Lab/atligator), installed from PyPI (“atligator”) and is implemented in Python 3.
A natural fungal gene drive enacts killing through targeting DNA
Authors: Urquhart Andrew S. , Gardiner Donald M. 
Published: January 2022

AbstractFungal spore-killers are a class of selfish genetic elements that positively bias their own inheritance by killing non-inheriting gametes following meiosis. As killing takes place specifically within the developing fungal ascus, a tissue which is experimentally difficult to isolate, our understanding of the mechanisms underlying spore killers are limited. In particular, how these loci kill other spores within the fungal ascus is largely unknown. Here we overcome these experimental barriers by developing model systems in two evolutionary distant organisms, Escherichia coli (bacterium) and Saccharomyces cerevisiae (yeast). Using these systems, we show that the Podospora anserina spore killer protein Spok1 enacts killing through targeting DNA.Significance StatementNatural gene drives have shaped the genomes of many eukaryotes and recently have been considered for applications to control undesirable species. In fungi these loci are called spore-killers. Despite their importance in evolutionary processes and possible applications our understanding of how they enact killing is limited. We show that the spore killer protein Spok1, which has homologues throughout the fungal tree of life, acts via DNA disruption. Spok1 is only the second spore killer locus in which the cellular target of killing has been identified and is the first known to target DNA. We also show that the DNA disrupting activity of Spok1 is functional in both bacteria and yeast suggesting a highly conserved mode of action.