bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoimmune hepatitis: Current and future therapeutic options
Authors: Doycheva Iliana , Watt Kymberly D. , Gulamhusein Aliya F. 
Published: February 2019

AbstractAutoimmune hepatitis (AIH) is a rare immune‐mediated liver disease with few major advances in treatment options over the last several decades. Available options are effective in most patients albeit are imprecise in their mechanisms. Novel and more tolerable induction regimens and alternative options for management of patients intolerant or with suboptimal response to traditional therapies including in the post‐transplant setting remain an important unmet need. This review aims to summarize recent data on pharmacological options and investigational drugs in development for patients with AIH. Standard therapy using prednisone with or without azathioprine remains the mainstay of therapy and is effective in most patients. Budesonide may be considered for induction in early disease and in those with mild fibrosis, but has not been approved for maintenance therapy. Mycophenolate mofetil (MMF) in combination with steroids might be an alternative first‐line therapy, but results from a randomized trial are awaited. MMF as a second‐line maintenance agent has moderate efficacy though more frequent adverse events in patients with cirrhosis may be seen. Tacrolimus may be an equally effective second‐line option particularly in non‐responders, but data remain limited. Management of recurrent AIH post‐liver transplantation remains controversial with insufficient data to support long‐term steroid use. Moving forward, expanding the scope of therapeutic options to include biologics including B‐cell depleting agents may be a promising step. Recent insights in understanding the pathogenesis of AIH could serve as a basis for future therapies, including the elucidation of different immunoregulatory pathways and the potential role of the intestinal microbiome.
Seed traits are pleiotropically regulated by the flowering time gene PERPETUAL FLOWERING 1 (PEP1) in the perennial Arabis alpina
Authors: Hughes Patrick William , Soppe Wim J. J. , Albani Maria C. 
Published: February 2019

AbstractThe life cycles of plants are characterized by two major life history transitions—germination and the initiation of flowering—the timing of which are important determinants of fitness. Unlike annuals, which make the transition from the vegetative to reproductive phase only once, perennials iterate reproduction in successive years. The floral repressor PERPETUAL FLOWERING 1 (PEP1), an ortholog of FLOWERING LOCUS C, in the alpine perennial Arabis alpina ensures the continuation of vegetative growth after flowering and thereby restricts the duration of the flowering episode. We performed greenhouse and garden experiments to compare flowering phenology, fecundity and seed traits between A. alpina accessions that have a functional PEP1 allele and flower seasonally and pep1 mutants and accessions that carry lesions in PEP1 and flower perpetually. In the garden, perpetual genotypes flower asynchronously and show higher winter mortality than seasonal ones. PEP1 also pleiotropically regulates seed dormancy and longevity in a way that is functionally divergent from FLC. Seeds from perpetual genotypes have shallow dormancy and reduced longevity regardless of whether they after‐ripened in plants grown in the greenhouse or in the experimental garden. These results suggest that perpetual genotypes have higher mortality during winter but compensate by showing higher seedling establishment. Differences in seed traits between seasonal and perpetual genotypes are also coupled with differences in hormone sensitivity and expression of genes involved in hormonal pathways. Our study highlights the existence of pleiotropic regulation of seed traits by hub developmental regulators such as PEP1, suggesting that seed and flowering traits in perennial plants might be optimized in a coordinated fashion.
Anisocoria caused by an abscess in the cisterna interpeduncularis in a patient with bacterial meningitis
Authors: Watanabe Toshiyuki Tony , Itaya Sakiko , Kamata Tomoyuki 
Published: February 2019

AbstractWhen bacterial meningitis is suspected in an emergency situation, a lumbar puncture is usually performed to obtain a cerebrospinal fluid culture for identifying the causative microorganism. However, in cases in which signs and symptoms of high intracranial pressure are obvious, lumbar puncture is contraindicated unless brain herniation is ruled out. We encountered a case of bacterial meningitis with anisocoria, which we regarded as a sign of high intracranial pressure, and refrained from performing a lumbar puncture. Subsequently, high intracranial pressure and brain herniation were ruled out, and abscess formation in the cisterna interpeduncularis was observed to have caused anisocoria. Thus, when anisocoria is observed in patients with bacterial meningitis, the cause should be established by methods such as magnetic resonance imaging, and only if the cause of anisocoria is obvious and the possibility of high intracranial pressure is low, should diagnostic lumbar puncture be performed.
The American neurogastroenterology and motility society gastroparesis cardinal symptom index‐daily diary (ANMS GCSI‐DD): Psychometric evaluation in patients with idiopathic or diabetic gastroparesis
Authors: Revicki Dennis A. , Speck Rebecca M. , Lavoie Sara , Puelles Jorge , Kuo Braden , Camilleri Michael , Almansa Cristina , Parkman Henry P. 
Published: February 2019

AbstractBackgroundThe purpose of this study was to evaluate the measurement properties of the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index‐Daily Diary, a patient‐reported outcome instrument developed to meet US FDA recommendations for a symptom‐based clinical trial endpoint in gastroparesis. The ANMS GCSI‐DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score from none (0) to very severe (4) and number of vomiting episodes during the past 24 hours. The composite score includes the first four symptoms, the core symptom score includes all five symptoms.MethodsSeventy‐one patients diagnosed with idiopathic or diabetic gastroparesis were recruited for a four‐week observational study. Patients completed the ANMS GCSI‐DD at home between Baseline and Week 4. Statistical analyses included confirmatory factor analysis, item response theory analysis, internal consistency, test‐retest reliability, and construct and known‐groups validity.Key ResultsUnidimensionality for the composite and core symptom scores was supported, and items exhibited good fit. Internal consistency (Cronbach's alpha =0.85 and 0.83) and test‐retest reliability were 0.89 and 0.88, for composite and core symptom scores, respectively. Convergent validity was supported by strong correlations with patient‐reported and clinician measures. Baseline and Week 4 scores differed for three measures used to define disease severity status (P < 0.0001), supporting known‐groups validity.Conclusions & InferencesThe ANMS GCSI‐DD has excellent reliability and validity, supporting its use to assess symptom‐based endpoints in gastroparesis clinical studies. Further analyses will be conducted using clinical trial data to ascertain treatment responsiveness and define a responder.
Seasonal and drought‐related changes in leaf area profiles depend on height and light environment in an Amazon forest
Authors: Smith Marielle N. , Stark Scott C. , Taylor Tyeen C. , Ferreira Mauricio L. , de Oliveira Eronaldo , Restrepo‐Coupe Natalia , Chen Shuli , Woodcock Tara , dos Santos Darlisson Bentes , Alves Luciana F. , Figueira Michela , de Camargo Plinio B. , de Oliveira Raimundo C. , Aragão Luiz E. O. C. , Falk Donald A. , McMahon Sean M. , Huxman Travis E. , Saleska Scott R. 
Published: February 2019

Summary

Seasonal dynamics in the vertical distribution of leaf area index (LAI) may impact the seasonality of forest productivity in Amazonian forests. However, until recently, fine‐scale observations critical to revealing ecological mechanisms underlying these changes have been lacking.

To investigate fine‐scale variation in leaf area with seasonality and drought we conducted monthly ground‐based LiDAR surveys over 4 yr at an Amazon forest site. We analysed temporal changes in vertically structured LAI along axes of both canopy height and light environments.

Upper canopy LAI increased during the dry season, whereas lower canopy LAI decreased. The low canopy decrease was driven by highly illuminated leaves of smaller trees in gaps. By contrast, understory LAI increased concurrently with the upper canopy. Hence, tree phenological strategies were stratified by height and light environments. Trends were amplified during a 2015–2016 severe El Niño drought.

Leaf area low in the canopy exhibited behaviour consistent with water limitation. Leaf loss from short trees in high light during drought may be associated with strategies to tolerate limited access to deep soil water and stressful leaf environments. Vertically and environmentally structured phenological processes suggest a critical role of canopy structural heterogeneity in seasonal changes in Amazon ecosystem function.
Efficacy of very low‐energy diet programs for weight loss: A systematic review with meta‐analysis of intervention studies in children and adolescents with obesity
Authors: Andela Sarah , Burrows Tracy L. , Baur Louise A. , Coyle Daisy H. , Collins Clare E. , Gow Megan L. 
Published: February 2019

SummaryThe objective of this review was to evaluate the efficacy and safety of very low‐energy diet (VLED) programs for weight loss in children and adolescents with obesity. Six electronic databases were searched identifying 24 eligible studies (16 pre‐post studies, four nonrandomized trials, two randomized controlled trials [RCTs], and two chart reviews) published up to October 2018. Studies were in English, implemented a VLED (≤3360 kJF/day [≤800 kcal/day] or <50% estimated energy requirements) in 5‐ to 18‐year‐olds with obesity, and reported at least one weight‐related outcome. Weight‐related outcomes significantly improved postintervention in all studies. Meta‐analysis of 20 studies indicated a mean 10.1 kg (95% confidence interval [CI], 8.7‐11.4 kg, P < 0.001; I2 = 92.3%) weight loss following interventions lasting 3 to 20 weeks. Moderator analysis indicated greater weight loss in adolescent‐only studies (10‐18 years) and formulated meal replacement interventions and inpatient settings. Meta‐analysis of seven studies reporting weight at follow‐up (5‐14.5 months from baseline) indicated 5.3 kg mean weight loss (CI, 2.5‐8.0 kg, P < 0.001; I2 = 50.6%). Details of adverse events were limited. VLED programs are effective for treating children and adolescents with obesity. However, conclusions on their safety cannot be drawn from the existing literature at this time. Future studies should include long‐term follow‐up with ongoing support and comprehensive monitoring of all adverse events.
Zoledronate treatment duration is linked to bisphosphonate‐related osteonecrosis of the jaw prevalence in rice rats with generalized periodontitis
Authors: Messer Jonathan G. , Jiron Jessica M. , Mendieta Calle Jorge L. , Castillo Evelyn J. , Israel Ronnie , Phillips Ean G. , Yarrow Joshua F. , Van Poznak Catherine , Kesavalu Lakshmyya , Kimmel Donald B. , Aguirre J. Ignacio 
Published: February 2019

AbstractObjectivesTo determine the extent that zoledronate (ZOL) dose and duration is associated with bisphosphonate‐related osteonecrosis of the jaw (BRONJ) prevalence in rice rats with generalized periodontitis (PD), characterize structural and tissue‐level features of BRONJ‐like lesions in this model, and examine the specific anti‐resorptive role of ZOL in BRONJ.Materials and MethodsRice rats (n = 228) consumed high sucrose‐casein diet to enhance generalized PD. Groups of rats received 0, 8, 20, 50 or 125 µg/kg IV ZOL/4 weeks encompassing osteoporosis and oncology ZOL doses. Rats from each dose group (n = 9–16) were necropsied after 12, 18, 24 and 30 weeks of treatment. BRONJ‐like lesion prevalence and tissue‐level features were assessed grossly, histopathologically and by MicroCT. ZOL bone turnover effects were assessed by femoral peripheral quantitative computed tomography, serum bone turnover marker ELISAs and osteoclast immunolabelling.ResultsPrevalence of BRONJ‐like lesions was significantly associated with (a) ZOL treatment duration, but plateaued at the lowest oncologic dose, and (b) there was a similar dose‐related plateau in the systemic anti‐resorptive effect of ZOL. ZOL and BRONJ‐like lesions also altered the structural and tissue‐level features of the jaw.ConclusionThe relationship between BRONJ‐like lesion prevalence and ZOL dose and duration varies depending on the co‐ or pre‐existing oral risk factor. At clinically relevant doses of ZOL, BRONJ‐like lesions are associated with anti‐resorptive activity.
DIET AND ENVIRONMENT IN SOUTH‐EASTERN IBERIA DURING THE BRONZE AGE, BASED ON ISOTOPE ANALYSIS OF HUMAN REMAINS
Authors: Molina‐González Fernando , Nocete‐Calvo Francisco , Delgado‐Huertas Antonio , Cámara‐Serrano Juan Antonio , Martínez‐Sánchez Rafael M. , Jiménez‐Brobéil Sylvia , Miranda‐León Mª. Teresa , Riquelme‐Cantal José Antonio , Spanedda Liliana , Pérez‐Bareas Cristóbal , Lizcano‐Prestel Rafael , Nieto‐Liñán José Miguel , Nájera‐Colino Trinidad , Granados‐Torres Arsenio , Carrión‐Méndez Francisco 
Published: February 2019

SummaryA large sample of human bones from a series of archaeological sites in the south‐eastern Iberian Peninsula was selected for δ13C and δ15N stable isotope analysis. Except for some contrast samples, the remains date from the first half of the second millennium cal BC and are ascribed to the Argar Culture, which developed during the Bronze Age in south‐eastern Iberia. Most authors have considered that this region reached a high degree of social hierarchical organization at this time, as demonstrated by the funerary record, both with regard to the grave goods and to the evidence of physical effort and diseases on the human remains. Results of the isotope analysis revealed the existence of differences among the settlements studied, as well as differences over time within every settlement and among the various individuals tested. Some variances can be assigned to social classes/status and others are linked to chronological factors. In particular, changes in δ13C can be explained by the increasing aridity of the first half of the second millennium cal BC, although other causes can be put forward too.
Ultrasound‐Guided Cervical Nerve Root Block for the Treatment of Acute Cervical Herpes Zoster: A Randomized Controlled Clinical Study
Authors: Zheng Shuyue , Li Xiuhua , Yang Xiaohui , He Liangliang , Xue Yanyan , Yang Zhanmin 
Published: February 2019

AbstractObjectivesTo evaluate the efficacy and safety of ultrasound‐guided cervical nerve root block (CRB) on acute pain and its preventive effects on post‐herpetic neuralgia (PHN) in patients with cervical herpes zoster (HZ).Methods140 recruited participants were randomized 1:1 to receive ultrasound‐guided CRB with either mixed drug liquid (treatment group) or similar looking placebo (placebo group). All patients received a 7‐day course of oral antiviral treatment, pregabalin, and analgesics as needed. The primary efficacy was assessed on the basis of HZ burden of illness (HZ‐BOI) scores over 30 days (BOI‐30AUC). Secondary outcomes included HZ‐BOI scores through 30 to 90 days (BOI‐30‐90AUC) and 90 to 180 days (BOI‐90‐180AUC), quality of life (QoL) outcomes, concomitant analgesic consumption, and the incidence of PHN. Adverse events were recorded to evaluate safety.ResultsThe BOI‐30AUC values were 92.55 and 112.72 for the treatment and placebo groups, respectively (P < 0.01). Both the BOI‐30‐90AUC and BOI‐90‐180AUC in the treatment group were lower than those in the placebo group (P < 0.01). The incidence of PHN at 90 days was significantly less than that at 180 days in the treatment group (P = 0.036). A better improvement in QoL was found in the treatment group (P < 0.05). There was a greater decrease in analgesic use in the treatment group as compared to the placebo group (P < 0.05). No serious adverse events were observed.ConclusionsUltrasound‐guided CRB represented an early intervention and preventive strategy to reduce the BOI due to acute HZ in the cervical dermatome region, and might be feasible to reduce the incidence of PHN.
Metacognitive improvement and symptom change in a 3‐month treatment for borderline personality disorder
Authors: Maillard Pauline , Dimaggio Giancarlo , Berthoud Laurent , de Roten Yves , Despland Jean‐Nicolas , Kramer Ueli 
Published: February 2019

ObjectivesRecognizing and reflecting on one's own and other people's mental states represent a major difficulty for patients with borderline personality disorder (BPD). Only recently have studies begun exploring whether these capacities increase with successful therapies and if such an improvement is linked with outcome. The present study investigated whether metacognition would improve and if its improvement was related with symptom change in BPD patients.DesignThe transcripts from the first and the penultimate session of a ten‐session version of good psychiatric management were analysed with the MAS‐R scale in a N = 37 BPD sample. Patients, selected from a previously published RCT (Kramer et al., 2014), were assigned either to the good psychiatric management treatment or to the same treatment with the addition of the Motive‐Oriented Therapeutic Relationship (Caspar, 2007), a form of therapeutic relationship based on an individualized case formulation. Symptoms were assessed with the OQ‐45.ResultsFindings partially support the hypotheses. First, improvement in capacities to understand others’ mind, to take a critical distance from one's own rigid and maladaptive beliefs, and to use behavioural and attentional strategies to face adversities is found in both treatment groups. Controlling for marital status, only the ability to differentiate between reality and representations remains significant. Second, no link between metacognitive change and symptom change during treatment is found. However, a link is observed between the increase in metacognition and symptom reduction at 6‐month follow‐up.ConclusionsResults invite to further investigate the role of metacognition in therapy change through different modalities and in longer‐term treatments.Practitioner points

The development of metacognitive processes and their links with symptom change were examined during a short‐term treatment in 37 borderline patients

Improvement was found in capacities to understand others’ mind, to take a critical distance from own rigid and maladaptive beliefs, and to use behavioural and attentional strategies even in a short‐term treatment

Controlling for marital status, only the ability to take a critical distance from representations remained significant

A link was observed between increase in metacognition and symptom reduction at 6‐month follow‐up

Understanding and tailoring interventions to specific metacognitive difficulties could be associated with symptom change during treatment for BPD patients.
Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities
Authors: Eroglu Zeynep , Holmen Sheri L. , Chen Qing , Khushalani Nikhil I. , Amaravadi Ravi , Thomas Reena , Ahmed Kamran A. , Tawbi Hussein , Chandra Sunandana , Markowitz Joseph , Smalley Inna , Liu James K. C. , Chen Yian Ann , Najjar Yana G. , Karreth Florian A. , Abate‐Daga Daniel , Glitza Isabella C. , Sosman Jeffrey A. , Sondak Vernon K. , Bosenberg Marcus , Herlyn Meenhard , Atkins Michael B. , Kluger Harriet , Margolin Kim , Forsyth Peter A. , Davies Michael A. , Smalley Keiran S. M. 
Published: February 2019

AbstractIn February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System (CNS) Metastases in Tampa, Florida. In this white paper, we outline the current status of basic science, translational, and clinical research into melanoma brain metastasis development and therapeutic management. We further outline the important challenges that remain for the field and the critical barriers that need to be overcome for continued progress to be made in this clinically difficult area.
Non‐invasive differentiation of non‐rejection kidney injury from acute rejection in pediatric renal transplant recipients
Authors: Archdekin Ben , Sharma Atul , Gibson Ian W. , Rush David , Wishart David S. , Blydt‐Hansen Tom D. 
Published: February 2019

AbstractAcute kidney injury (AKI) is a major concern in pediatric kidney transplant recipients, where non‐alloimmune causes must be distinguished from rejection. We sought to identify a urinary metabolite signature associated with non‐rejection kidney injury (NRKI) in pediatric kidney transplant recipients. Urine samples (n = 396) from 60 pediatric transplant participants were obtained at time of kidney biopsy and quantitatively assayed for 133 metabolites by mass spectrometry. Metabolite profiles were analyzed via projection on latent structures discriminant analysis. Mixed‐effects regression identified laboratory and clinical predictors of NRKI and distinguished NRKI from T cell–mediated rejection (CMR), antibody‐mediated rejection (AMR), and mixed CMR/AMR. Urine samples (n = 199) without rejection were split into NRKI (n = 26; ΔSCr ≥25%), pre‐NRKI (n = 35; ΔSCr ≥10% and <25%), and no NRKI (n = 138; ΔSCr <10%) groups. The NRKI discriminant score (dscore) distinguished between NRKI and no NRKI (AUC = 0.86; 95% CI = 0.79‐0.94), confirmed by leave‐one‐out cross‐validation (AUC = 0.79; 95% CI = 0.68‐0.89). The NRKI dscore also distinguished between NRKI and pre‐NRKI (AUC = 0.82; 95% CI = 0.71‐0.93). In a linear mixed‐effects regression model to account for repeated measures, the NRKI dscore was independent of concurrent rejection, but there was a non‐statistical trend for higher dscores with rejection severity. A second exploratory classifier developed to distinguish NRKI from clinical rejection had similar test characteristics (AUC = 0.81, 95% CI = 0.70‐0.92, confirmed by LOOCV). This study demonstrates the potential of a urine metabolite classifier to detect NRKI in pediatric kidney transplant patients and non‐invasively discriminate NRKI from rejection.