bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-31 expression in HIV-infected patients with different routes of disease transmission
Authors: Yan Changxin , Xu Huafeng , Rong Chunli , Cao Meilin , Miao Zhuo , Zhou Haizhou 
Published: June 2022

Abstract
Acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV). AIDS is characterized by an impaired immune system and low cellular immunity. The main manifestation of AIDS is a reduction in the number of CD4+ T cells and alteration in cytokine concentration. The present work aimed to explore the expression of IL-31 in HIV infection and disease progression.
Serum samples were collected from HIV-infected patients with different routes of disease transmission. The subjects included 24 patients who were infected with HIV upon blood transmission and 36 patients who had acquired the disease through sexual transmission (21 cases of homosexual transmission and 15 cases of heterosexual transmission). In addition, 20 normal healthy individuals were included to serve as the control group. The levels of IL-31 in the collected serum samples were estimated using the human IL-31 Platinum ELISA kit.
The serum analysis results revealed that the concentration of IL-31 in the serum samples for the blood transmission, sexually transmission, and normal group patients was 4.07 ± 1.63 pg/L, 7.43 ± 1.15 pg/L, and 2.87 ± 1.04 pg/L, respectively. The statistical analysis revealed that the concentration of IL-31 in HIV-1 infection was higher than that in the normal control. In addition, the expression of IL-31 was significantly higher in the sexual transmission group compared to the blood transmission group (P < .05).
IL-31 could have an important role in HIV infection, although the role of IL-31 in disease progression in HIV-infected individuals requires further research.
A Study of Postoperative Complications Occurring at Home With Pediatric Gastrostomy Feeding Tubes
Authors: Aedla Mihika , Zhou Anson , Sompel Kevin , Hu Katherine , Cheng Charlotte , Hsu Jocelyn , Qian Jason , Zhang Siya , Ho Anthony , Slagle Jacob , Logsdon Elizabeth A. , Sharma Karun V. , Weiss Clifford R. 
Published: June 2022

Objective:
Gastrostomy tubes (G-tubes) provide long-term feeding assistance to children with severe feeding dysfunction. Although there are a host of complications that occur at home with current pediatric G-tube feeding, their prevalences and outcomes remain relatively unstudied. This study aims to identify and describe such complications.

Methods:
A dual-round survey was administered to 98 participants through the Feeding Tube Awareness Foundation, a 501(c)(3) organization that supports parents and caretakers of G-tube-fed children. Information was collected broadly regarding G-tube complications, causes, and attitudes toward such complications.

Results:
Infection (56%), itching/irritation/redness (52%), and leakage (51%) were the leading G-tube related complications. The average time that G-tubes were replaced was 3.4 ± 1.2 months as compared to the typical recommended period of up to 6 months. Of the caretakers who had not experienced G-tube displacement, 7.9% wanted to see a change in current G-tubes to address the issue, compared with 75% of those who had experienced displacement. This 67.1% differential in caretakers’ attitudes toward G-tubes based on their prior experience with a particular complication was the largest gap among all other listed complications.

Conclusions:
G-tube complications are prevalent and varied. A sizable portion of G-tube users experience complications severe enough to require intervention. Of these, G-tube displacement is particularly critical and frequently precedes other prevalent complications, namely gastric leakage, infection, and tissue granulation.
Autoimmune Antibodies in Children and Adolescents With Nonalcoholic Fatty Liver Disease
Authors: Kohut Taisa , Shah Amit , Russo Pierre , Panganiban Jennifer 
Published: June 2022

Objectives:
The clinical significance of autoantibody positivity in nonalcoholic fatty liver disease (NAFLD) in the absence of autoimmune hepatitis (AIH) remains uncertain. We aimed to determine the prevalence of autoantibodies in a pediatric cohort with biopsy-proven NAFLD and investigate the association between autoantibodies and NAFLD histologic grade.

Methods:
Single-center, retrospective study of patients ≤21 years with biopsy-proven NAFLD from 2014 to 2019. Clinical and laboratory data were obtained within 90 days of liver biopsy. Autoantibody positivity was defined as serum titer ≥1:80 or units ≥20. Liver biopsies were evaluated for features of AIH, then scored for steatosis, hepatocyte ballooning, lobular inflammation, and NAFLD activity score (NAS) was calculated. Portal inflammation and fibrosis were scored separately. Multivariable logistic regression was used for continuous and binary outcomes.

Results:
Sixty-seven subjects met inclusion criteria. Positive antinuclear antibody (ANA), antismooth muscle antibody (ASMA), antineutrophil cytoplasmic antibody (ANCA), anti-F-actin antibody (F-actin), anti-liver kidney microsomal (LKM) antibody, or any combination was observed in 43%, 39%, 19%, 13%, 0%, and 66% of subjects, respectively. After controlling for confounders, positive ANA and alanine aminotransferase (ALT) >80 had 4.6 greater odds of having an NAS ≥5 (P = 0.035; 95% confidence interval [CI], 1.12–19.01). Autoantibody positivity resolution occurred in 10%–50% who underwent serial monitoring.

Conclusions:
Autoantibodies, except LKM, were frequently encountered in our pediatric NAFLD cohort in the absence of AIH. ANA positivity with ALT may help clinically stratify pediatric patients with suspected NAFLD targeting those at greater risk for nonalcoholic steatohepatitis (NASH).
Methotrexate for Primary Maintenance Therapy in Mild-to-Moderate Crohn Disease in Children
Authors: Baldwin Katherine , Goldfarb Alexa , Brimacombe Michael , Hopkins Dena , Hyams Jeffrey S. 
Published: June 2022

Objectives:
Despite limited data, methotrexate (MTX) is often used as primary maintenance therapy in pediatric Crohn disease (CD). We sought to assess the effectiveness of MTX as “initial” primary maintenance therapy in newly diagnosed mild/moderate pediatric CD and ascertain baseline predictive factors.

Methods:
Single-center 10-year retrospective review of newly diagnosed CD patients treated with MTX as primary maintenance therapy. We compared baseline characteristics of those patients with sustained response/clinical remission to those patients who escalated to anti-TNF therapy within 1 year. Pediatric Crohn Disease Activity Index (PCDAI) ≤ 10 defined remission.

Results:
We identified 65 patients (mean age, 11.8 years; 72 % male; mean ± SD PCDAI, 17.8 ± 10.5) who started MTX ≤4 months of diagnosis as their primary maintenance therapy. Initial therapy prior to MTX was corticosteroids (CS) (54/65), defined diet (4/65), and combination CS/diet (6/65). Oral dosing was used in 55%; mean dose was 11.4 mg/m2 orally and 12.5 mg/m2 subcutaneously. At 1 year, 36 of 65 (55%) were on MTX monotherapy, and of those, 32 of 36 were in clinical remission; 81% were in steroid-free remission for the year following induction. For the 36 patients on MTX at 1 year, 14 (39%) had gross mucosal healing (22% of the original cohort). Ten additional patients had mucosal improvement (37% of total healed/improved). Fifteen patients (23%) were early failures, transitioning to anti-TNF ≤4 months. Baseline PCDAI, hemoglobin, ESR, albumin, and route of administration were not predictive of outcome. MTX was well tolerated in our cohort, with only 1 patient stopping due to elevated aminotransferases. No patient required CD surgery in the 1-year follow-up.

Conclusions:
MTX may have a primary maintenance role in mild/moderate CD.
Indirect and Out-of-Pocket Disease-associated Costs in Pediatric Inflammatory Bowel Disease: A Cross-sectional Analysis
Authors: El-Matary Wael , Witt Julia , Bernstein Charles N. , Jacobson Kevan , Mack David , Otley Anthony , Walters Thomas D. , Huynh Hien Q. , deBruyn Jennifer , Griffiths Anne M. , Benchimol Eric I. 
Published: June 2022

Objectives:Data on pediatric inflammatory bowel disease (IBD)-associated indirect and out-of-pocket (OOP) costs are limited. We aimed to estimate indirect (lost work hours and productivity) and OOP pediatric IBD-associated costs in Canada.Methods:In a nation-wide cross-sectional analysis, caregivers of children with IBD were invited to complete a questionnaire on lost work hours and OOP costs related to IBD in the 4 weeks prior to the survey. Participants were reinvited to periodically answer the same questionnaire every 3–9 months for 2 years. Lost productivity was calculated using the Human Capital method. Costs were reported in 2018 inflation-adjusted Canadian dollars. Predictors of high cost users (top 25%) were examined using binary logistic regression.Results:Consecutive 243 (82 incident cases) of 262 (92.7%) approached participants completed the first survey with a total of 450 surveys longitudinally completed over 2 years. The median annual indirect cost per patient was $5966 (IQR $1809–$12,676), with $5721 (IQR $1366–$11,545) for Crohn’s disease (CD) and $7007 (IQR $2428–$14,057) for ulcerative colitis (UC) (P= 0.11). The annual median per patient OOP costs were $4550 with $4550 for CD and $5038 for UC (P= 0.53). Longer travel distance to clinic was associated with higher OOP costs (odds ratio = 4.55;P< 0.0001; 95% confidence interval: 1.99–10.40).Conclusions:Indirect and OOP IBD-associated costs are substantial and more likely to affect families living in remote communities.
An agonistic monoclonal antibody targeting cMet attenuates inflammation and upregulates collagen synthesis and angiogenesis in Type 2 diabetic mouse wounds
Authors: Choi Min-Ha , Jang Tae-Sik , Kim Hyeonwoo , Ku Inhoe , Lee Junghun , Jeong Jae-Gyun , Kim Sunyoung , Park Ji-Ung 
Published: June 2022

Background:
Diabetic wounds account for 25%–50% of total diabetic healthcare costs annually, and present overall healing rates of less than 50%. Since delayed diabetic wound healing is associated with impaired fibroblast function, we hypothesize that tyrosine kinase Met (cMet) agonistic monoclonal antibody (mAb) will promote diabetic wound healing via stable activation of HGF/cMet signaling.

Methods:
Two 6 mm dorsal wounds were created in each mice (6-week-old, male BKS.Cg-Dock7m+/+Leprdb/J, n=5). After subcutaneous injections of agonist (20 mg/kg) at 0 and 72h, the wound sizes were measured at days 0, 1, 3, 6, and 10. Histological and immunohistochemical analyses were performed at day 10 (cMet, α-SMA, CD68, and TGF-β). In vitro cytotoxicity and migration tests with diabetic fibroblasts were performed with/without agonist treatment (1 or 10 nM). cMet pathway activation of fibroblasts was confirmed through p-p44/42MAPK, p-mTOR, p-cMet, and ROCK-1 expression.

Results:
cMet agonistic mAb-treated group showed 1.60-fold lower wound area (p=0.027), 1.54-fold higher collagen synthesis (p=0.001), and 1.79-fold lower inflammatory cell infiltration (p=0.032) than the saline-treated control. The agonist increased cMet (1.86-fold, p=0.029), α-SMA (1.20-fold, p=0.018), and VEGF (1.68-fold, p=0.029) expression but suppressed CD68 (1.25-fold, p=0.043), TFG-β (1.25-fold, p=0.022), and MMP-2 (2.59-fold, p=0.029) expression. In vitro agonist treatment (10 nM) of diabetic fibroblasts increased their migration by 8.98-fold (p=0.029) and activated HGF/cMet pathway.

Conclusions:
cMet agonistic mAb treatment improved diabetic wound healing in mice and reduced wound-site inflammatory cell infiltration. These results need to be validated in large animals before piloting human trials.
Impact of Ischemia Duration on Lower Limb Salvage in Combat Casualties
Authors: Perkins Zane B. , Kersey Alexander J. , White Joseph M. , Lauria Alexis L. , Propper Brandon W. , Tai Nigel R.M. , Rasmussen Todd E. 
Published: June 2022

Introduction:
The 6-hour threshold to revascularization of an ischemic limb is ubiquitous in the trauma literature, however, contemporary evidence suggests that this threshold should be less. This study aims to characterize the relationship between the duration of limb ischemia and successful limb salvage following lower extremity arterial trauma.

Methods:
This is a cohort study of the United States and UK military service members injured while serving in Iraq or Afghanistan between 2003 and 2013. Consecutive patients who sustained iliac, femoral, or popliteal artery injuries, and underwent surgery to attempt revascularization, were included. The association between limb outcome and the duration of limb ischemia was assessed using the Kaplan-Meier method.

Results:
One hundred twenty-two patients (129 limbs) who sustained iliac (2.3%), femoral (56.6%), and popliteal (41.1%) arterial injuries were included. Overall, 87 limbs (67.4%) were successfully salvaged. The probability of limb salvage was 86.0% when ischemia was ≤1 hour; 68.3% when between 1 and 3 hours; 56.3% when between 3 and 6 hours; and 6.7% when >6 hours (P<0.0001). Shock more than doubled the risk of failed limb salvage [hazard ratio=2.42 (95% confidence interval: 1.27–4.62)].

Conclusions:
Limb salvage is critically dependent on the duration of ischemia with a 10% reduction in the probability of successful limb salvage for every hour delay to revascularization. The presence of shock significantly worsens this relationship. Military trauma systems should prioritize rapid hemorrhage control and early limb revascularization within 1 hour of injury.
Ecological complexity and the biosphere: the next 30 years
Authors: Solé Ricard , Levin Simon 
Published: June 2022

Global warming, habitat loss and overexploitation of limited resources are leading to alarming biodiversity declines. Ecosystems are complex adaptive systems that display multiple alternative states and can shift from one to another in abrupt ways. Some of these tipping points have been identified and predicted by mathematical and computational models. Moreover, multiple scales are involved and potential mitigation or intervention scenarios are tied to particular levels of complexity, from cells to human–environment coupled systems. In dealing with a biosphere where humans are part of a complex, endangered ecological network, novel theoretical and engineering approaches need to be considered. At the centre of most research efforts is biodiversity, which is essential to maintain community resilience and ecosystem services. What can be done to mitigate, counterbalance or prevent tipping points? Using a 30-year window, we explore recent approaches to sense, preserve and restore ecosystem resilience as well as a number of proposed interventions (from afforestation to bioengineering) directed to mitigate or reverse ecosystem collapse. The year 2050 is taken as a representative future horizon that combines a time scale where deep ecological changes will occur and proposed solutions might be effective.
This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.
Is the genomics ‘cart’ before the restoration ecology ‘horse’? Insights from qualitative interviews and trends from the literature
Authors: Mohr Jakki J. , Harrison Peter A. , Stanhope Jessica , Breed Martin F. 
Published: June 2022

Harnessing new technologies is vital to achieve global imperatives to restore degraded ecosystems. We explored the potential of genomics as one such tool. We aimed to understand barriers hindering the uptake of genomics, and how to overcome them, via exploratory interviews with leading scholars in both restoration and its sister discipline of conservation—a discipline that has successfully leveraged genomics. We also conducted an examination of research trends to explore some insights that emerged from the interviews, including publication trends that have used genomics to address restoration and conservation questions. Our qualitative findings revealed varied perspectives on harnessing genomics. For example, scholars in restoration without genomics experience felt genomics was over-hyped. Scholars with genomics experience emphatically emphasized the need to proceed cautiously in using genomics in restoration. Both genomics-experienced and less-experienced scholars called for case studies to demonstrate the benefits of genomics in restoration. These qualitative data contrasted with our examination of research trends, which revealed 70 restoration genomics studies, particularly studies using environmental DNA as a monitoring tool. We provide a roadmap to facilitate the uptake of genomics into restoration, to help the restoration sector meet the monumental task of restoring huge areas to biodiverse and functional ecosystems.
This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.
Complexity–biodiversity relationships on marine urban structures: reintroducing habitat heterogeneity through eco-engineering
Authors: Bishop Melanie J. , Vozzo Maria L. , Mayer-Pinto Mariana , Dafforn Katherine A. 
Published: June 2022

Urbanization is leading to biodiversity loss through habitat homogenization. The smooth, featureless surfaces of many marine urban structures support ecological communities, often of lower biodiversity, distinct from the complex natural habitats they replace. Eco-engineering (design for ecological co-benefits) seeks to enhance biodiversity and ecological functions on urban structures. We assessed the benefits to biodiversity of retrofitting four types of complex habitat panels to an intertidal seawall at patch (versus flat control panels) and site (versus unmodified control seawalls and reference rocky shores) scales. Two years after installation, patch-scale effects of complex panels on biodiversity ranged from neutral to positive, depending on the protective features they provided, though all but one design (honeycomb) supported unique species. Water-retaining features (rockpools) and crevices, which provided moisture retention and cooling, increased biodiversity and supported algae and invertebrates otherwise absent. At the site scale, biodiversity benefits ranged from neutral at the high- and mid-intertidal to positive at the low-intertidal elevation. The results highlight the importance of matching eco-engineering interventions to the niche of target species, and environmental conditions. While species richness was greatest on rockpool and crevice panels, the unique species supported by other panel designs highlights that to maximize biodiversity, habitat heterogeneity is essential.
This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.
Arginase 1 is a key driver of immune suppression in pancreatic cancer
Authors: Menjivar Rosa E. , Nwosu Zeribe C. , Du Wenting , Donahue Katelyn L. , Espinoza Carlos , Brown Kristee , Velez-Delgado Ashley , Yan Wei , Lima Fatima , Bischoff Allison , Kadiyala Padma , Salas-Escabillas Daniel , Crawford Howard , Bednar Filip , Carpenter Eileen , Zhang Yaqing , Halbrook Christopher J. , Lyssiotis Costas A. , Pasca di Magliano Marina 
Published: June 2022

AbstractAn extensive fibroinflammatory stroma rich in macrophages is a hallmark of pancreatic cancer. In this disease, it is well appreciated that macrophages are immunosuppressive and contribute to the poor response to immunotherapy; however, the mechanisms of immune suppression are complex and not fully understood. Immunosuppressive macrophages are classically defined by expression of the enzyme Arginase 1 (Arg1), which we demonstrated is potently expressed in pancreatic tumor associated macrophages from both human patients and mouse models. While routinely used as a polarization marker, Arg1 also catabolizes arginine, an amino acid required for T cell activation and proliferation. To investigate this metabolic function, we used a genetic and a pharmacologic approach to target Arg1 in pancreatic cancer. Genetic inactivation of Arg1 in macrophages, using a dual recombinase genetically engineered mouse model of pancreatic cancer, delayed formation of invasive disease, while increasing CD8+ T cell infiltration. Treatment of established tumors with the arginase inhibitor CB-1158 exhibited further increased CD8+ T cell infiltration, beyond that seen with the macrophage-specific knockout, and sensitized the tumors to anti-PD1 immune checkpoint blockade. Thus, our data demonstrate that Arg1 is more than simply a marker of macrophage function. Rather, Arg1 is also a driver of immune suppression and represents a promising immunotherapeutic target for pancreatic cancer.
Linking microenvironment modification to species interactions and demography in an alpine plant community
Authors: Ray Courtenay A. , Kapas Rozalia E. , Opedal Øystein H. , Blonder Benjamin W. 
Published: June 2022

AbstractIndividual plants can modify the microenvironment within their spatial neighborhood. However, the consequences of microenvironment modification for demography and species interactions remain unclear at the community scale. In a study of co-occurring alpine plants, we (1) determined the extent of species-specific microclimate modification by comparing temperature and soil moisture between vegetated and non-vegetated microsites for several focal species. We (2) determined how vital rates (survival, growth, fecundity) of all species varied in response to aboveground and belowground vegetative overlap with inter- and intraspecific neighbors as proxies for microenvironment modification. For (1), surface temperatures were buffered (lower maximums and higher minimums) and soil moisture was higher below the canopies of most species compared to non-vegetated areas. For (2), vegetative overlap predicted most vital rates, although the effect varied depending on whether aboveground or belowground overlap was considered. Vital rate response to microenvironment-modification proxies (vegetative overlap) was also frequently context dependent with respect to plant size and macroclimate. Microenvironment modification and spatial overlapping of individuals are key drivers of demography and species interactions in this alpine community.
A disease model for Diffuse Intrinsic Pontine Glioma (DIPG) with mutations in TP53 and its application for drug repurposing
Authors: Yuryev Anton , Nesterova Anastasia , Sozhin Sergey , Shkrob Maria 
Published: June 2022

1.1AbstractBrain cancers are ones of most aggressive and difficult to treat cancers. Despite numerous studies of the cellular mechanisms of gliomas, it is difficult to stop tumor growth. A complex genetic and epigenetic nature of many gliomas and poorly known pathways of human neuron precursors maturation suggest turning to big data analysis to find new insights and directions for drug development. We developed in silico molecular models and predicted molecular switches in signaling cascades that maintain multipotency of neuronal precursor cells in diffuse intrinsic pontine glioma (DIPG) driven by the H3K27M mutation and mutations in the TP53 gene. Oncogenes and biomarkers were predicted based on transcriptomics and mutational genomics data from a cohort of 30 patients with DIPG analyzed using Elsevier artificial intelligence methods and a collection of manually curated cancer hallmark pathways. The molecular models of DIPG with mutations in TP53 and histone 3 gene describe the mechanism of oligodendrocyte dedifferentiation due to activation of transcriptional factors OLIG2, SOX2 and POU5F1, epithelial-to-mesenchymal transition via strong EGFR and TGFR signaling, enhanced cell response to hypoxia via HIF1A signaling, and enhanced angiogenesis by VEGFA overexpression. Using in silico analysis, we identified drugs capable of inhibiting mutant TP53: vorinostat, cisplatin, paclitaxel, and statins were top ranked drugs. The predicted drugs and oncogenes had individual patient-level differences that can be visualized with created DIPG model and may be useful for future research in the field of personalized medicine.