bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colectomy Incidence Rates in Five-Year Data From the Observational Postmarketing Ulcerative Colitis Study of Originator Infliximab
Authors: Panés Julián , Lindsay James O , Teich Niels , Lindgren Stefan , Colombel Jean-Frédéric , Flynn Heather Ann , Huyck Susan , Yao Ruji , Philip George , Reinisch Walter 
Published: February 2021

Abstract

Background
This analysis of the Observational Postmarketing Ulcerative Colitis Study examined incidence rates of colectomy in patients with ulcerative colitis who received originator infliximab (IFX) or conventional therapies (ConvRx) as per their treating physician.

Methods
Cox proportional hazards models compared time to colectomy for both treatment groups. A secondary analysis examined colectomy incidence rates based on IFX exposure timing (defined by a 90-day window after the last IFX dose date).

Results
Of 2239 patients with data, 1059 enrolled in IFX and 1180 enrolled in ConvRx (including 296 patients who switched to IFX). Patients in the IFX group had more severe disease at baseline vs the ConvRx group (percentage with baseline partial Mayo score 7-9: 46.0% vs 30.5%, respectively). During 5 years of follow-up, 271 patients (12.1% of enrolled patients) had colectomy. Enrollment in the IFX group was associated with a higher risk of colectomy (hazard ratio = 3.12; 95% confidence interval, 2.25-4.34; P &lt; 0.001) compared with enrollment in the ConvRx group. A total of 174 colectomies occurred in the IFX group, but 97 of these colectomies occurred ≥90 days after the last IFX dose date.

Conclusions
Colectomy was reported at a higher rate in the IFX group than in the ConvRx group, although patients in the IFX group had more severe disease at baseline and most of the colectomies occurred after patients had been off of IFX for ≥90 days.
Blunt traumatic thoracic aortic injuries: a retrospective cohort analysis of 2 decades of experience
Authors: Prendes Carlota Fernandez , Stana Jan , Schneidwind Karina Domingos , Rantner Barbara , Konstantinou Nikolaos , Bruder Jan , Kammerlander Christian , Banafsche Ramin , Tsilimparis Nikolaos 
Published: February 2021

Abstract

OBJECTIVES
The aim of this study was to analyse and report the changes in the management of blunt traumatic aortic injuries (BTAIs) in a single centre during the last 2 decades.

METHODS
A retrospective analysis of all patients diagnosed with BTAI from January 1999 to January 2020 was performed. Data were collected from electronic/digitalized medical history records.

RESULTS
Forty-six patients were included [median age 42.4 years (16–84 years), 71.7% males]. The predominant cause of BTAI was car accidents (54.5%, n = 24) and all patients presented with concomitant injuries (93% bone fractures, 77.8% abdominal and 62.2% pelvic injuries). Over 70% presented grade III or IV BTAI. Urgent repair was performed in 73.8% of patients (n = 31), with a median of 2.75 h between admission and repair. Thoracic endovascular repair (TEVAR) was performed in 87% (n = 49), open surgery (OS) in 10.9% (n = 5) and conservative management in 2.1% (n = 1). Technical success was 82.6% (92.1% TEVAR, 79% OS). In-hospital mortality was 19.5% (17.5% TEVAR, 40% OS). Of these, 3 died from aortic-related causes. Seven (15.2%) required an early vascular reintervention. The median follow-up was 34 months (1–220 months), with 19% of early survivors having a follow-up of &gt;10 years. Only 1 vascular reintervention was necessary during follow-up: secondary TEVAR due to acute graft thrombosis. Of the patients who survived the initial event, 6.7% died during follow-up, none from aortic-related causes.

CONCLUSIONS
Even with all the described shortcomings, in our experience TEVAR for BTAI proved to be feasible and effective, with few complications and stable aortic reconstruction at mid-term follow-up. With the current technical expertise and wide availability of a variety of devices, it should be pursued as a first-line therapy in these challenging scenarios.
Divisor Varieties of Symmetric Products
Authors: Sheridan John 
Published: February 2021

Abstract
The geometry of divisors on algebraic curves has been studied extensively over the years. The foundational results of this Brill-Noether theory imply that on a general curve, the spaces parametrizing linear series (of fixed degree and dimension) are smooth, irreducible projective varieties of known dimension. For higher dimensional varieties, the story is less well understood. Our purpose in this paper is to study in detail one class of higher dimensional examples where one can hope for a quite detailed picture, namely (the spaces parametrizing) divisors on the symmetric product of a curve.
Presence of Pathogen-killed Larvae Influences Nesting Behavior of the Alfalfa Leafcutting Bee (Hymenoptera: Megachilidae)
Authors: Klinger Ellen G , Welker Dennis L , James Rosalind R 
Published: February 2021

Abstract
The alfalfa leafcutting bee (Megachile rotundata (Fabricius)), a commercial pollinator used for alfalfa seed production, is susceptible to chalkbrood disease via ingested fungal spores. Diseases of insects can elicit behavioral changes in their hosts, but there are no recorded behaviors of alfalfa leafcutting bees in response to this fungal exposure. We conducted field studies to determine whether bees in pathogen-dense environments altered their nesting patterns, specifically if bees exposed to fungal spores produced higher numbers of nest cells and whether the proportions of nest cells that failed as eggs or small larvae (a state known as ‘pollen ball’) were greater. We found that our control bees, nontreated bees which were not exposed to chalkbrood spores other than those in the natural environment, had the highest proportion of pollen ball cells. Bees experimentally exposed to infective spores created the lowest number of nests and the fewest cells. Bees experimentally exposed to heat killed noninfective spores produced the greatest number of nests and cells overall and the greatest number of healthy progeny. We conclude that there are underlying behaviors that are elicited in response to the presence of chalkbrood spores that reduce the proportion of failed nest cells (grooming) and increase retention of bees at nesting sites (delay of bee emergence). Through further study of these behaviors, bee managers can potentially increase the productivity of their bee populations.
Feminist Overview of International Investment Law—A Preliminary Inquiry
Authors: Sinha Amit Kumar , Anand Pushkar 
Published: February 2021

ABSTRACT
There have not been many studies to evaluate the tenets of international investment law from a feminist perspective. Thus, a study from a feminist perspective is not only desirable but also necessary to understand the position of women in this regime. To fill this gap, the article presents an analysis of the normative and structural frameworks of international investment law from a feminist standpoint. This article finds that women are under-represented in the structural framework of international investment law, and the normative framework barely touches upon the issues of women. The article suggests measures to gender-mainstream the investment law regime. It concludes that gender inclusiveness of the international investment regime can only be achieved when international investment policymaking is complemented by a flexible but robust municipal structure that supports gender equality and women’s participation in economic activities.
Eugenol modulates insulin sensitivity by upregulating insulin receptor substrate-2 in non-alcoholic fatty liver disease in rats
Authors: Fawzy Mariam H , Saeed Noha M , El-Sherbiny Doaa A , El-Demerdash Ebtehal 
Published: February 2021

Abstract

Objectives
The purpose of this study was to estimate the possible modulatory effect of Eugenol (EUG) on insulin resistance (IR) and liver fibrosis in high-fat diet (HFD)-induced experimental non-alcoholic fatty liver disease (NAFLD) in rats. It has been shown that EUG, a natural phenolic compound, has anti-hyperglycaemic, antioxidant and anti-inflammatory actions.

Methods
For 8 consecutive weeks, standard rat chow diet (control group, EUG only treated group) or HFD (HFD group and HFD+EUG-treated group) were fed to rats daily. HFD+EUG-treated group and EUG only treated group were administered EUG (10 mg/kg) orally three times per week. Various indices of hepatotoxicity, oxidative stress, indicators of inflammation and liver fibrosis were investigated.

Key findings
HFD-induced liver transaminases and triglycerides (TGs) were significantly decreased and histopathological lesions were improved with EUG treatment. EUG significantly improved IR evoked by HFD, as demonstrated by Homeostasis model assessment for insulin resistance (HOMA-IR) and increased insulin receptor substrate-2 (IRS-2) sensitivity. In addition, EUG improved oxidative stress damage elicited by HFD as shown by the restoration of reduced glutathione (GSH) level and nuclear factor erythroid-2-related factor 2 (Nrf-2) expression and plummeting lipid peroxidation. Further, EUG lessened pro-inflammatory cytokines surge [tumour necrosis factor-α (TNF-α) and IL-6] via inhibiting nuclear factor-κB (NF-κB) stimulation. As markers of fibrosis, EUG reduced collagen accumulation and smooth muscle alpha actin (SMaA) and TGF-β expression.

Conclusions
EUG may have protective effect against progression of fibrosis in NAFLD. The antifibrotic effect of EUG is probably due to EUG’s antioxidant, anti-inflammatory and anti-hyperglycaemic.
Design and characterisation of an amorphous formulation of nifedipine for the treatment of autonomic dysreflexia
Authors: Browne Emer , Quinn Sian , Cheyne Sheena , Healy Anne Marie 
Published: February 2021

Abstract

Objectives
Current treatment for autonomic dysreflexia (AD) involves rupturing a liquid-filled soft capsule of nifedipine to aid rapid drug release and absorption, however, this application is not covered under the manufacturer's license. The objective of the current work was to design a rapidly dissolving solid dosage formulation for the treatment of AD as an alternative to the off-license “bite and swallow” use of currently available commercial products.

Methods
Amorphous solid dispersions (ASDs) of nifedipine were prepared by spray-drying using three different polymers: hydroxypropyl methyl cellulose (HPMC), polyvinyl pyrrolidone (PVP) and polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol (Soluplus), at a 15% w/w drug loading and were formulated and compressed into tablets. Dissolution testing was performed in the paddle dissolution apparatus using either a monophasic or biphasic medium.

Key findings
The PVP–nifedipine ASD tablets exhibited rapid dissolution, with 35% of the total nifedipine dose dissolving within 15 min in the monophasic dissolution medium. The HPMC–nifedipine ASD exhibited a very slow dissolution, while the Solupus–nifedipine system exhibited no nifedipine release over 120 min. When tested in the biphasic dissolution medium, the PVP–nifedipine ASD tablets exhibited a release profile comparable to that of the pre-split/ruptured nifedipine soft capsule product.

Conclusions
This study demonstrates that a nifedipine–PVP ASD is a promising formulation strategy in the treatment of AD.
Does the management of woody edges in urban parks match aesthetic and ecological user perception?
Authors: Bergerot Benjamin , Hellier Emmanuelle , Burel Françoise 
Published: February 2021

AbstractIn recent times, the focus in urban park management has shifted from mere aesthetics to the difficult task of striking a balance between ecology and the aesthetic outlay of those parks. Park managers design the spatial arrangement, the structure and the ecological diversity of vegetation to mimic natural ecosystems. However, the ecological benefit is often associated with a decrease in the aesthetic value for users. To better understand this trade-off, we eye-tracked 196 users in Rennes (France) to test if ‘ecological’ management of woody edges was in accordance with their aesthetic preferences and ecological perception. We identified which were the visual areas of interest for users in four types of managed woody edges and analysed which were considered as the most aesthetic and the most ecologically valuable. Finally, we analysed if both aesthetic user preferences and ‘ecological’ management of woody edges were compatible. Based on a classification of increasing management complexity of woody edges, we showed that users’ aesthetic preferences were mainly focused on tree and shrub layers, while users identified the herb and shrub layers as the most favourable area for maintaining biodiversity. Thus, the more complex the edge, the more the relationship between aesthetic preferences and ecological management is for park management. More precisely, in complex woody edge structures, some vegetation layers such as shrub could represent a specific lever to fulfil both aesthetic and ecological purposes.
Phase I trial of intranasal NEO100, highly purified perillyl alcohol, in adult patients with recurrent glioblastoma
Authors: Schönthal Axel H , Peereboom David M , Wagle Naveed , Lai Rose , Mathew Anna J , Hurth Kyle M , Simmon Vincent F , Howard Steven P , Taylor Lynne P , Chow Frances , da Fonseca Clovis O , Chen Thomas C 
Published: February 2021

Abstract

Background
Better treatments for glioblastoma (GBM) patients, in particular in the recurrent setting, are urgently needed. Clinical trials performed in Brazil indicated that intranasal delivery of perillyl alcohol (POH) might be effective in this patient group. NEO100, a highly purified version of POH, was current good manufacturing practice (cGMP) manufactured to evaluate the safety and efficacy of this novel approach in a Phase I/IIa clinical trial in the United States.

Methods
A total of 12 patients with recurrent GBM were enrolled into Phase I of this trial. NEO100 was administered by intranasal delivery using a nebulizer and nasal mask. Dosing was 4 times a day, every day. Four cohorts of 3 patients received the following dosages: 96 mg/dose (384 mg/day), 144 mg/dose (576 mg/day), 192 mg/dose (768 mg/day), and 288 mg/dose (1152 mg/day). Completion of 28 days of treatment was recorded as 1 cycle. Adverse events were documented, and radiographic response via Response Assessment in Neuro-Oncology (RANO) criteria was evaluated every 2 months. Progression-free and overall survival were determined after 6 and 12 months, respectively (progression-free survival-6 [PFS-6], overall survival-12 [OS-12]).

Results
Intranasal NEO100 was well tolerated at all dose levels and no severe adverse events were reported. PFS-6 was 33%, OS-12 was 55%, and median OS was 15 months. Four patients (33%), all of them with isocitrate dehydrogenase 1 (IDH1)-mutant tumors, survived &gt;24 months.

Conclusion
Intranasal glioma therapy with NEO100 was well tolerated. It correlated with improved survival when compared to historical controls, pointing to the possibility that this novel intranasal approach could become useful for the treatment of recurrent GBM.
Genetic syndromes predisposing to pediatric brain tumors
Authors: Farouk Sait Sameer , Walsh Michael F , Karajannis Matthias A 
Published: February 2021

AbstractThe application of high-throughput sequencing approaches including paired tumor/normal sampling with therapeutic intent has demonstrated that 8%-19% of pediatric CNS tumor patients harbor a germline alteration in a classical tumor predisposition gene (NF1, P53). In addition, large-scale germline sequencing studies in unselected cohorts of pediatric neuro-oncology patients have demonstrated novel candidate tumor predisposition genes (ELP1 alterations in sonic hedgehog medulloblastoma). Therefore, the possibility of an underlying tumor predisposition syndrome (TPS) should be considered in all pediatric patients diagnosed with a CNS tumor which carries critical implications including accurate prognostication, selection of optimal therapy, screening, risk reduction, and family planning. The Pediatric Cancer Working Group of the American Association for Cancer Research (AACR) recently published consensus screening recommendations for children with the most common TPS. In this review, we provide an overview of the most relevant as well as recently identified TPS associated with the most frequently encountered pediatric CNS tumors with an emphasis on pathogenesis, genetic testing, clinical features, and treatment implications.
Chronotropic effects and mechanisms of long-chain omega-3 polyunsaturated fatty acids on heartbeat: the latest insights
Authors: Zhang Weiguo 
Published: February 2021

Abstract
The roles of the resting heart rate (RHR) have been actively investigated and increasingly recognized in recent decades, because of the growing evidence that fast RHR is associated with and predicts the risk of developing cardiovascular and metabolic disorders, as well as all-cause mortality. Long-chain omega-3 polyunsaturated fatty acids (PUFAs) (eg, eicosapentaenoic acid and docosahexaenoic acid) have been shown to have chronotropic effects on heartbeat in both healthy people and patients with various disease conditions. The aims of this review are (1) to briefly summarize the importance of elevated RHR in disease pathogenesis and mortality; (2) to provide an update on the negative chronotropic effect of omega-3 PUFAs on the heart; (3) to highlight how omega-3 PUFAs regulate heart rate through the autonomic nervous system – a central control mechanism; and (4) to highlight how omega-3 PUFAs modulate the trans-membrane ionic channels in cardiomyocytes – a fundamental mechanism of cardiac automaticity. Eicosapentaenoic acid and docosahexaenoic acid are nutrients derived from some aquatic organisms, and they can also be converted from digested oily seeds and nuts of some terrestrial plants in the body. The consumption of omega-3 PUFAs for RHR reduction represents a lifestyle modification for risk factor management and promises nutritional benefits for public health improvement.
The Effect of Antibiotic Restriction Programs on Prevalence of Antimicrobial Resistance: A Systematic Review and Meta-Analysis
Authors: Schuts Emelie C , Boyd Anders , Muller Anouk E , Mouton Johan W , Prins Jan M 
Published: February 2021

AbstractBackgroundIn hospital settings, restriction of selected classes of antibiotics is usually believed to contribute to containment of resistance development. We performed a systematic review and meta-analysis to assess the effect of restricting the use of specific antibiotic classes on the prevalence of resistant bacterial pathogens.MethodsWe conducted a systematic literature search in Embase and PubMed/OVID MEDLINE. We included studies until June 4, 2020 in which a restrictive antibiotic policy was applied and prevalence of resistance and use of antibiotics were reported. We calculated the overall effect of antimicrobial resistance between postintervention versus preintervention periods using pooled odds ratios (ORs) from a mixed-effects model. We stratified meta-analysis by antibiotic-pathogen combinations. We assessed heterogeneity between studies using the I2 statistic and sources of heterogeneity using meta-regression.ResultsWe included 15 individual studies with an overall low quality of evidence. In meta-analysis, significant reductions in resistance were only observed with nonfermenters after restricting fluoroquinolones (OR = 0.77, 95% confidence interval [CI] = 0.62–0.97) and piperacillin-tazobactam (OR = 0.81, 95% CI = 0.72–0.92). High degrees of heterogeneity were observed with studies restricting carbapenem (Enterobacterales, I2 = 70.8%; nonfermenters, I2 = 81.9%), third-generation cephalosporins (nonfermenters, I2 = 63.3%), and fluoroquiolones (nonfermenters, I2 = 64.0%). Results were comparable when excluding studies with fewer than 50 bacteria. There was no evidence of publication bias for any of the antibiotic-pathogen combinations.ConclusionsWe could not confirm that restricting carbapenems or third-generation cephalosporins leads to decrease in prevalence of antibiotic resistance among Enterobacterales, nonfermenters, or Gram-positive bacteria in hospitalized patients. Nevertheless, reducing fluoroquinolone and piperacilline-tazobactam use may decrease resistance in nonfermenters.
Solving the mystery of HBV-related mixed cryoglobulinemia: potential biomarkers of disease progression
Authors: Pocino Krizia , Napodano Cecilia , Gragnani Laura , Ciasca Gabriele , Colantuono Stefania  , Marri Silvia , Vantaggio Lorenzo , Gulli Francesca , Lorini Serena , Barini Antonella , Stefanile Annunziata , Miele Luca , Casato Milvia , Zignego Anna Linda , Rapaccini Gian Ludovico , Marino Mariapaola , Visentini Marcella , Basile Umberto 
Published: February 2021

AbstractObjectivesThe biomarkers of an immunological dysregulation due to a chronic HBV infection are indeed understudied. If untreated, this condition may evolve into liver impairment co-occurring with extrahepatic involvements. Here, we aim to identify a new panel of biomarkers [including immunoglobulin G (IgG) subclasses, RF, and Free Light Chains (FLCs)] that may be useful and reliable for clinical evaluation of HBV-related cryoglobulinemia.MethodsWe retrospectively analysed clinical data from 44 HBV-positive patients. The patients were stratified (according to the presence/absence of mixed cryoglobulinemia) into two groups: 22 with cryoglobulins (CGs) and 22 without CGs. Samples from 20 healthy blood donors (HDs) were used as negative controls. Serum samples were tested for IgG subclasses, RF (-IgM, -IgG, and -IgA type), and FLCs.ResultsWe detected a strikingly different distribution of serum IgG subclasses between HDs and HBV-positive patients, together with different RF isotypes; in addition, FLCs were significantly increased in HBV-positive patients compared with HDs, while no significant difference was shown between HBV-positive patients with/without mixed cryoglobulinemia.ConclusionThe immune-inflammatory response triggered by HBV may be monitored by a peculiar profile of biomarkers. Our results open a new perspective in the precision medicine era; in these challenging times, they could also be employed to monitor the clinical course of those COVID-19 patients who are at high risk of HBV reactivation due to liver impairment and/or immunosuppressive therapies.
Thymus variants on imaging in patients with rheumatoid arthritis—clinical and immunological significance
Authors: Murata Okinori , Suzuki Katsuya , Sugiura Hiroaki , Kondo Yasushi , Takeshita Masaru , Koga Keiko , Takiguchi Maiko , Kurisu Rina , Kassai Yoshiaki , Yasuoka Hidekata , Yamaoka Kunihiro , Morita Rimpei , Yoshimura Akihiko , Takeuchi Tsutomu 
Published: February 2021

Abstract

Objectives
We sought to clarify the presence of radiographic thymus variants using a scoring system, and their association with clinical and immunological features in RA patients.

Methods
A total of 387 RA patients were randomly selected from all patients visiting our department who underwent chest CT scanning, with exclusion of patients with thymoma or thymic cyst, or age &lt; 30 years. Thymus size and attenuation score in axial CT images were quantitatively interpreted and assessed. Associations between immunophenotype data and clinical and serological features were analysed in a subset of patients.

Results
Thymic enlargement was found in 76 (19.6%) patients, and a thymus attenuation score ≥ 2 was found in 50 (12.9%) patients. The score was significantly associated with antibodies to ACPA positivity. Thymic enlargement was significantly associated with the proportions of CD4+ effector memory T cells.

Conclusion
Radiographic thymus variants were frequently observed in RA patients and may reflect an abnormal immune response involved in the pathogenesis of RA.