bluuebunny/crossref_metadata_2025_split huggingface dataset:
OXPHOS DRIVES CRYPT FISSIONING REQUIRED FOR HEALING OF IBD ULCERS
Authors: Abomhya Ahmed , Goretsky Tatiana , Kapur Neeraj , Perry Courtney , Avdiushko Margarita , Bradford Emily , Barrett Terrence 
Published: January 2022

Abstract

INTRODUCTION
The failure of ulcers healing is a characteristic feature of IBD. Mitochondrial dysfunction in intestinal epithelial cells (IEC) occurs in IBD and is linked to worse clinical outcomes in pediatric Crohn’s and ulcerative colitis (Kugrathasan et al Lancet 2017, Haberman et al Nat Comm 2019). Cellular polarization and maintenance of cell polarity are energy-dependent and highly regulated by mitochondrial biogenesis (Hardie DG et al Genes Dev 2011). Yet, it is unclear how mitochondria participate in mucosal repair.

METHODS
To model mitochondrial deficiency, TFAM, a transcriptional factor needed for mitochondrial DNA (mtDNA)-encoded genes was silenced in human colonoids (shTFAM) and VilCre/mTmG/TFAMfl/fl (IEC-TFAM-/-) mice. Levels of crypt branching and intestinal stem cell (ISC) and mitochondrial gene mRNA levels were assessed in colonoids cultured in Wnt-containing (WENR) media. Effects on IEC mitochondrial complex levels and oxygen consumption rates (OCR) were assessed in control IEC-TFAM-/- mice and effects on disease activity and ulcer healing assessed in DSS colitis IEC-TFAM-/- mice (fed DSS x 7d, peak ulcer healing-D13-15). Dual florescence confocal microscopy examined crypt fissioning and IHC in WT (Tom+) and Tfamfl/fl (GFP+) crypts during windows of peak ulcer healing.

RESULTS
shTFAM-treated colonoids expressed 55-92% lower mitochondrial gene mRNA (Cox6A1, mt-CO1, ATP5A1) levels (p&lt;0.01) {A} and displayed reduced size (35%) and budding (86%) compared to WT cells (p&lt;0.005) {B}. Studies on IEC from IEC-TFAM-/- mice revealed lower mitochondrial complex protein levels {C i-iv}, and &gt;65% lower mtDNA (p&lt;0.01) {D} compared to controls that correlated with 43 and 65% lower IEC OCR (using Oroboros). In DSS mice, levels of ulceration were greater in IEC-TFAM-/- mice (25%) compared to WT (7.5%) (P&lt;0.005). More importantly, levels of crypt fissioning were 85% lower in TFAM-deficient (GFP+) compared to WT (Tom+) crypts {E}. WT fissioning crypt stained for SOX9 {F} and nuclear pβCat552 {G}.

CONCLUSION
Together, these results suggest that IEC mitochondrial deficiency as seen in IBD patients, impairs crypt fissioning during ulcer healing through a process that impairs cooperation between Wnt and PI3K signaling pathways. The data argue that therapeutic improvement of mitochondrial function may enhance mucosal repair in IBD by promoting crypt fissioning needed to re-establish barrier function.
A NOVEL MICROBIALLY-DERIVED PROTEIN CAN BE EXPRESSED INLACTOCOCCUS LACTIS AND DELIVERED ORALLY TO IMPROVE GUT BARRIER FUNCTION AND PREVENT FIBROGENESIS BY INTERACTING WITH THE EXTRACELLULAR MATRIX DURING GI INJURY
Authors: La Chat Chip La , Nigatu Eskedar , Messner Elisabeth , Raja Bernat Baeza , Desnoyer Jill , Johnson Amy Jo , Willcoxon Michi , Banas Stefanie , Han Andrew , DeSantis Todd , Dabbagh Karim , Shilova Irina , Yamamoto Lynn 
Published: January 2022

Abstract
Intestinal barrier dysfunction or the loss of the epithelial integrity allowing the permeation of microorganisms, dietary antigens and other particles into the gastrointestinal (GI) mucosa results in the activation of the immune system and drives inflammation during IBD. Ongoing inflammation in the GI tract and loss of the mucosal barrier are key features of active disease and predict relapse and serious complications. Existing drugs approved in IBD have limited effects on endoscopic remission and improvement in mucosal healing, driving a critical need for therapies which lead directly to mucosal healing. We have identified a microbial protein, SG-2-0776, that directly improves barrier function and reduces fibrogenesis in vitro and in vivo with potential to become a driver of mucosal healing. SG-2-0776 was identified through a novel algorithm, multi-technology meta-analysis (MTMA), using mucosal biopsies from UC patients and control subjects. Two bacterial strains, Eubacterium eligens and Roseburia hominis were significantly reduced in UC samples. Screening of proteins predicted to be secreted from these strains using in vitro transepithelial/endothelial electrical resistance (TEER) and wound healing assays, identified SG-2-0776, a novel protein, which significantly improved epithelial barrier integrity and reduced fibrogenesis. Administration of recombinant SG-2-0776 protein showed improvement in intestinal barrier function, reduced inflammation and fibrosis in rodent models of colitis. Moreover, SG-2-0776 was expressed in Lactococcus lactis as a delivery vehicle and administered orally to act locally for therapeutic effects in these models of colitis. Mechanism of action studies demonstrated that SG-2-0776 interacts with extracellular matrix proteins regulating myofibroblasts differentiation, leading to reduced fibrogenic phenotypes. Altogether, these results demonstrate SG-2-0776 has the potential, as a standalone or adjunct therapy to existing treatments, to ameliorate mucosal barrier function and prevent fibrogenesis in IBD patients.
THE MICROBIAL LANDSCAPE OF ULCERATIVE COLITIS IN ENDOSCOPIC REMISSION
Authors: Jangi Sushrut , Robison Glenn , Sebastiani Paola , Crott Jimmy , Weinstock Joel , Singh Siddharth , Michaud Dominique 
Published: January 2022

Abstract

BACKGROUND
Achieving endoscopic remission (Mayo endoscopic score of 1 or 0) appears to be the optimal clinical target in ulcerative colitis, reducing risk of relapse, hospitalizations, complications, and need for surgery. While attaining complete endoscopic remission (MES 0) appears to reduce these risks further over mild endoscopic activity (MES 1), the etiologic factors for why MES 0 might be the superior target is poorly understood. Given the putative role of the gut microbiome in driving underlying endoscopic activity and subsequent relapse risk, we sought to define the microbial landscape of UC among patients who achieve either MES 0 vs MES 1 endoscopic remission, especially since the colonic microbial constituents of UC in remission remain uncharacterized.

METHODS
We performed a retrospective cohort study, utilizing data from The Study of a Prospective Adult Research Cohort with IBD (SPARC IBD), part of the IBD Plexus network established by the Crohn’s and Colitis Foundation. SPARC IBD is a national, multi-center, longitudinal cohort study enrolling eligible (&gt;= 18 years) patients with IBD that includes demographic and disease specific clinical data, endoscopic scores, and stool metagenomics. To examine the microbiome, we evaluated beta-diversity (Bray-curtis dissimilarity), and phylum and genera-level differential taxal abundance, utilizing linear models (limma), between patients with UC in either MES 1 vs MES 0 endoscopic remission. Statistical analysis was performed using phyloseq and limma packages in R (ver 4.1).

RESULTS
Within the SPARC cohort, we identified 77 patients in endoscopic remission (48 with MES 0, 29 with MES 1), of which 52% were female and 91% white, with median age of 48. Patients in MES 0 or MES 1 had no significant differences in exposure to anti-TNF therapy (50% vs 50%), vedolizumab (25% vs 19%) or mesalamine (69% vs 72%). Beta-diversity was similar between MES 0 and MES 1 remission [Figure 1]. Both MES 1 and MES 0 remission were dominated by Bacteroidetes and Firmicutes, and were specifically abundant for Bacteroides uniformis, unclassified Subdoligranulum, and Akkermansia mucuniphila. Compared to MES 1 remission, patients with MES 0 remission had increased abundance of Bacteroidetes, Firmicutes, and Actinobacteria, but reduced levels of Proteobacteria and Verrucomicrobia, although after adjusting for multiple comparisons, differential abundance at the phylum and taxa-level between both groups were comparable [Figure 2].

CONCLUSIONS
The microbial landscape of ulcerative colitis in MES 1 vs MES 0 endoscopic remission is comparable with respect to beta-diversity, phylum and genera-level differential taxal abundance. Further investigation will include comparison of UC in remission to healthy controls, and whether the presence of specific microbial groups in remission can predict subsequent relapse.
PREVALENCE AND IMPACTS OF POST-TRAUMATIC STRESS SYMPTOMS IN IBD PATIENTS FROM UNDER-REPRESENTED MINORY GROUPS
Authors: McGarva Josie , Taft Tiffany 
Published: January 2022

Abstract

INTRODUCTION
Post Traumatic Stress (PTS) is a chronic psychological condition that occurs in response to a traumatic event, and includes symptoms of re-experiencing, avoidance behaviors, changes in mood, and hyperarousal. Left untreated, PTS is associated with poor outcomes and significant impairments in quality of life (HRQoL). Recent studies find 20-30% of IBD patients report significant PTS symptoms due to IBD experiences. The majority of participants in these studies are white, non-Hispanic making results difficult to generalize to other populations. As such, we aim to characterize IBD related PTS in under-represented minority (URM) patients.

METHODS
Adult patients 18+ who identify as a URM (Latino/a, African American, Asian, Middle Eastern, Native American or Native Pacific Islander) recruited via social media and researchmatch.org website completed an anonymous online survey: demographics, disease information, Harvey Bradshaw Index (HBI) or simple clinical colitis activity index (SCCAI) with &gt;4 = active IBD, NIH-PROMIS QoL module (fatigue, sleep disturbance, social isolation, pain interreference), and PTSD Checklist-5 (PCL5) with &gt;30 = suggested IBD-PTS, with subscale scores. Independent samples t-Test, Pearson’s correlation, and hierarchical linear regression statistics were used.

RESULTS
67 participants: 46% UC, 79% female, 73% South/Southeast Asian, 6% Hispanic, Age (Mean±SD) = 35.42±9.79 years. 55% had active IBD (HBI/SCCAI &gt; 4; 5.57±4.51). 43% scored &gt;30 on PCL5. Specifically, 55.2% reported re-experiencing trauma, 59.7% avoiding trauma triggers, 62.7% mood changes/irritability, and 67.2% autonomic hyperarousal. Patients with active IBD reported higher IBD-PTS (p=.001) as well as more fatigue, sleep disturbance, pain interference, and social isolation (all p&lt;.001); no differences by IBD diagnosis, gender, or age. When controlling for HBI/SCCAI score, IBD-PTS severity was a significant predictor, but smaller than disease severity, of fatigue (β=.223, p=.025) and pain interference (β=.254, p=.006), and a larger predictor of sleep disturbance (β=.424, p&lt;.001) and social isolation (β= -.417, p&lt;.001). Only the PTS symptoms of hyperarousal and mood contributed to these relationships.

CONCLUSION
43% of URM met criteria for PTS, and scored above 50% in each symptom category of the PCL-5, suggesting URM patients are at even higher risk for IBD-related PTS. Despite disease severity, IBD-PTS severity predicted fatigue, pain interference, sleep disturbance, and social isolation domains of HRQoL; mood changes or hyperarousal presence appear to be the most important symptoms to address. IBD-PTS could have a greater influence on HRQoL than disease activity and should be assessed in patients with both active and inactive disease. More research is necessary to evaluate this relationship and the prevalence of IBD-PTS in URM.
‘Adaptation science’ is needed to inform the sustainable management of the world's oceans in the face of climate change
Authors: Hidalgo Manuel , Bartolino Valerio , Coll Marta , Hunsicker Mary E , Travers-Trolet Morgane , Browman Howard I 
Published: January 2022

AbstractThe global response to the challenge of increasingly rapid and severe climate change is shifting from a focus on mitigation and remediation of impacts to a pragmatic adaptation framework. Innovative adaptive solutions that transform the way in which we manage the world's oceans and, particularly, the harvesting of marine resources in a sustainable manner, are urgently needed. In that context, ICES Journal of Marine Science solicited contributions to the themed article set (TS), “Exploring adaptation capacity of the world's oceans and marine resources to climate change”. We summarize the contributions included in this TS that provide examples of emerging climate change impacts, assess system risks at subnational and international scales, prove and evaluate different adaptation options and approaches, and explore societal and stakeholder perceptions. We also provide some “food for thought" on possible future developments in a transdisciplinary “adaptation science” working at the interface between ecology, socio-economics, and policy-governance, and that will have to provide concrete solutions to the challenges represented by climate-change and anthropogenic activity. Success will depend on the extent to which new knowledge and approaches can be integrated into the decision-making process to support evidence-based climate policy and ecosystem-based management. This includes testing their effectiveness in real systems, but also consider how social acceptance of adaptive measures will/will not support their full implementation.
Weight Gain After Smoking Cessation and Cancer Risk in 3 Prospective Cohorts in the United States
Authors: Hu Yang , Zong Geng , Sun Qi , Giovannucci Edward , Song Mingyang 
Published: January 2022

Abstract

Background
It remains unknown how cancer risks vary by duration of smoking cessation and whether the benefit is attenuated by postcessation weight gain.

Methods
We prospectively followed 198 565 persons from the Nurses’ Health Study (1978-2016), Nurses’ Health Study II (1991-2017), and Health Professionals Follow-up Study (1988-2016) who were free of cancer at baseline. We used proportional hazard Cox models to compare cancer risk between current smokers and former smokers with different durations of smoking cessation and postcessation weight gains.

Results
During 4 718 199 person-years of follow-up, we identified 32 456 cases of total cancer. Compared with current smokers, the risks for total and smoking-related cancer in past smokers were reduced to the level similar to never smokers after abstaining smoking for more than 26 years, with the hazard ratio of 0.69 (95% confidence interval [CI] = 0.63 to 0.76) for total cancer and 0.31 (95% CI = 0.26 to 0.37) for smoking-related cancer, whereas no risk reduction was found for obesity-related cancer. Comparing former smokers with current smokers, the multivariable-adjusted hazard ratios for postcessation weight gain of 0-4.9 kg, 5-9.9 kg, and 10 kg or higher were 0.85 (95% CI = 0.81 to 0.89), 0.88 (95% CI = 0.83 to 0.93), and 0.93 (95% CI = 0.88 to 1.00) for total cancer and 0.62 (95% CI = 0.58 to 0.67), 0.65 (95% CI = 0.60 to 0.71), and 0.71 (95% CI = 0.65 to 0.78) for total smoking-related cancer. In contrast, higher weight gain following smoking cessation was associated with a modest increased obesity-related cancer risk.

Conclusion
Smoking cessation overall has a strong net association with lower risk of total cancer irrespective of weight gain. However, this inverse association may be attenuated by substantial postcessation weight gain, largely because of an increased risk of obesity-related cancers.
Overexpression mutants reveal a role for a chloroplast MPD protein in regulation of reactive oxygen species during chilling in Arabidopsis
Authors: Lunn Daniel , Smith Gracen A , Wallis James G , Browse John 
Published: January 2022

Abstract
Reactive oxygen species (ROS) contribute to cellular damage in several different contexts, but their role during chilling damage is poorly defined. Chilling sensitivity both limits the distribution of plant species and causes devastating crop losses worldwide. Our screen of chilling-tolerant Arabidopsis (Arabidopsis thaliana) for mutants that suffer chilling damage identified a gene (At4g03410) encoding a chloroplast Mpv17_PMP22 protein, MPD1, with no previous connection to chilling. The chilling-sensitive mpd1-1 mutant is an overexpression allele that we successfully phenocopied by creating transgenic lines with a similar level of MPD1 overexpression. In mammals and yeast, MPD1 homologs are associated with ROS management. In chilling conditions, Arabidopsis overexpressing MPD1 accumulated H2O2 to higher levels than wild-type controls and exhibited stronger induction of ROS response genes. Paraquat application exacerbated chilling damage, confirming that the phenotype occurs due to ROS dysregulation. We conclude that at low temperature increased MPD1 expression results in increased ROS production, causing chilling damage. Our discovery of the effect of MPD1 overexpression on ROS production under chilling stress implies that investigation of the nine other members of the Mpv17_PMP22 family in Arabidopsis may lead to new discoveries regarding ROS signaling and management in plants.
H-band temperature and metallicity indicators for cool giants empirical relations in bayesian framework
Authors: Ghosh Supriyo , Ninan J P , Ojha D K 
Published: January 2022

ABSTRACT
We explored here the near-infrared H-band atmospheric window aiming to provide quantitative diagnostic tools for deriving stellar parameters, for instance, effective temperature (Teff) and metallicity ([Fe/H]), of cool giants (Teff &lt; 5000 K) using low-resolution spectra. We obtained 177 cool giants from the X-shooter spectral library covering a wider metallicity range (−2.35 dex &lt; [Fe/H] &lt; 0.5 dex) than in earlier works. Degrading the spectral resolution to R ∼ 1200, we estimated equivalent widths of several important spectral features, and the behaviour of spectral features with stellar parameters are studied. Also, the empirical relations for deriving Teff and [Fe/H] are established in the Bayesian framework. We found that 12CO at 1.56 and 1.62 $\mu$m, and 12CO + MgI at 1.71 $\mu$m are the best threeTeff indicators with a typical accuracy of 153, 123, and 107 K, respectively. The cubic Bayesian model provides the best metallicity estimator with a typical accuracy of 0.22, 0.28, and 0.24 dex for FeH at 1.62 $\mu$m, 12CO at 1.64 $\mu$m, and Fe I at 1.66 $\mu$m, respectively. We also showed a detailed quantitative metallicity dependence ofTeff–EWs correlations defining three metallicity groups, supersolar ([Fe/H] &gt; 0.0 dex), solar (−0.3 dex &lt; [Fe/H] &lt; 0.3 dex), and subsolar ([Fe/H] &lt;−0.3 dex), from Hierarchical Bayesian modelling. The difference between the solar and subsolar relationship is statistically significant, but such difference is not evident between the solar and supersolar groups.
Out of one, many: distinguishing time delays from lensed supernovae
Authors: Denissenya Mikhail , Bag Satadru , Kim Alex G , Linder Eric V , Shafieloo Arman 
Published: January 2022

ABSTRACT
Gravitationally lensed Type Ia supernovae are an emerging probe with great potential for constraining dark energy, spatial curvature, and the Hubble constant. The multiple images and their time delayed and magnified fluxes may be unresolved, however, blended into a single light curve. We demonstrate methods without a fixed source template matching for extracting the individual images, determining whether there are one (no lensing) or two or four (lensed) images, and measuring the time delays between them that are valuable cosmological probes. We find 100 per cent success for determining the number of images for time delays greater than ∼10 d.
Deuterium chemistry and D/H ratios in Class 0/I proto-brown dwarfs
Authors: Riaz B , Thi W-F 
Published: January 2022

ABSTRACT
We have conducted the first extensive observational survey of several deuterated species in 16 Class 0/I proto-brown dwarfs (proto-BDs) and 4 Class Flat/Class II brown dwarfs. Observations were obtained with the IRAM 30m telescope in the DCO+ (3–2), DCN (3–2), DNC (3–2), and N2D+ (3–2) lines. The DCO+/H13CO+, DCN/H13CN, and DNC/HN13C ratios are comparatively higher and show a narrower range than the DCO+/HCO+, DCN/HCN, and DNC/HNC ratios, respectively. The mean D/H ratios for the proto-BDs derived from these molecules are in the range of ∼0.02–3. Both low-temperature gas-phase ion-molecule deuteron transfer and grain surface reactions are required to explain the enhanced deuterium fractionation. The very dense and cold ($n_{H_{2}} \ge 10^{6}$ cm−3, T ≤10 K) interior of the proto-BDs provide the suitable conditions for efficient deuterium fractionation in these cores. There is no correlation between the D/H ratios and the CO depletion factor, with the exception of the DCN/HCN ratios that show a strong anti-correlation possibly due to the difference in the peak emitting regions of the DCN and HCN molecules. Over a wide range in the bolometric luminosities spanning ∼0.002–40 L⊙, we find a trend of higher DCO+/HCO+ and DCN/HCN ratios, nearly constant DNC/HNC and DNC/HN13C ratios, and lower N2D+/N2H+ ratios in the proto-BDs compared to protostars. Only one Class II brown dwarf shows emission in the DCO+ (3–2) line. No correlation is seen between the D/H ratios and the evolutionary stage.
A principal component analysis of polycyclic aromatic hydrocarbon emission in NGC 7023
Authors: Sidhu Ameek , Bazely Josh , Peeters Els , Cami Jan 
Published: January 2022

ABSTRACT
We carried out a principal component analysis (PCA) of the fluxes of five polycyclic aromatic hydrocarbon (PAH) bands at 6.2, 7.7, 8.6, 11.0, and 11.2 µm in the reflection nebula NGC 7023 comprising of the photodissociation region (PDR) and a cavity. We find that only two principal components (PCs) are required to explain the majority of the observed variance in PAH fluxes ( 98 per cent). The first PC ( PC1), which is the primary driver of the variance, represents the total PAH emission. The second PC (PC2) is related to the ionization state of PAHs across the nebula. This is consistent with the results of a similar analysis of the PAH emission in NGC 2023. The biplots and the correlations of PCs with the various PAH ratios show that there are two subsets of ionic bands with the 6.2 and 7.7 µm bands forming one subset and the 8.6 and 11.0 µm bands the other. However, the distinction between these subsets is only present in the PDR. We have also carried out a separate PCA analysis of the PAH fluxes, this time only considering variations in the cavity. This shows that in the cavity, PC2 is not related to the charge state of PAHs but possibly to structural molecular changes.
The DRAKE mission: finding the frequency of life in the Cosmos
Authors: Sarkar Subhajit 
Published: January 2022

ABSTRACT
In the search for life in the Universe, exoplanets represent numerous natural experiments in planet formation, evolution, and the emergence of life. This raises the fascinating prospect of evaluating cosmic life on a statistical basis. One key statistic is the occurrence rate of life-bearing worlds, fL, the ‘frequency of life’ term in the famous Drake Equation. Measuring fL would give profound insight into how common life is and may help us to constrain origin-of-life theories. I propose fL as the goal for the DRAKE mission (Dedicated Research for Advancing Knowledge of Exobiology): a transit spectroscopy survey of M-dwarf habitable zone terrestrial planets. I investigate how the uncertainty on the observed value of fL scales with sample size. I determine that sampling error dominates over observational error and that the uncertainty is a function of the observed fL value. I show that even small sample sizes can provide significant constraints on fL, boding well for the transit spectroscopy approach. I perform a feasibility study of the DRAKE mission using a nominal instrument design and mission plan. Due to low observing efficiencies, DRAKE may need to be incorporated into a wider-ranging deep-space or lunar observatory. A 50-planet survey could constrain fL to ≤ 0.06 (at 95 per cent confidence) if the sample fL  = 0, or 0.03–0.2 if the sample fL  = 0.1. This can be achieved (on average) in 10 yr using a 17-m telescope with an unrestricted field-of-regard. DRAKE is a viable approach to attempting the first experimental measurement of fL.