bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of dual-point fluorine-18 fluorodeoxyglucose PET imaging, partial volume correction and glucose transporter-1 expression in resected nonsmall cell lung cancer patients.
Authors: Kaida Hayato , Azuma Koichi , Kawahara Akihiko , Takamori Shinzo , Akiba Jun , Fujimoto Kiminori , Ishii Kazunari , Ishibashi Masatoshi 
Published: November 2019

Objective
To investigate the relationship between the prognosis and glucose transporter-1 (Glut-1) expression or fluorine-18 fluorodeoxyglucose uptake using partial volume correction and dual-point imaging in surgically resected nonsmall cell lung cancer (NSCLC) patients.

Methods
Our patient population consisted of 108 NSCLC cases. The early maximum standardized uptake value (ESUVmax), delayed SUVmax (DSUVmax), partial volume correction SUVmax (cSUVmax) and retention index of primary lesions were calculated. Cox proportional hazard model was applied to evaluate the effects of PET parameters and Glut-1 expression. Overall survival (OS) and disease-free survival (DFS) were evaluated by Kaplan–Meier methods, and the difference in survival between subgroups was analyzed by log-rank test.

Results
On the Cox regression analysis, ESUVmax, DSUVmax, cSUVmax and Glut-1 were significantly related to DFS [ESUVmax, hazard ratio
= 2.301, 95% confidential interval (CI) = 1.146–4.618, P = 0.019; DSUVmax, hazard ratio = 2.483, 95% CI = 1.257–4.905, P = 0.009; cSUVmax, hazard ratio = 2.205, 95% CI = 1.038–4.686, P = 0.04; Glut-1, hazard ratio = 2.095, 95% CI = 1.086–4.041, P = 0.001] and OS (ESUVmax, hazard ratio = 3.197, 95% CI = 1.339–7.633, P = 0.009; DSUVmax, hazard ratio = 3.599, 95% CI = 1.521–8.516, P = 0.004; cSUVmax, hazard ratio = 8.655, 95% CI = 2.048–36.658, P = 0.003; Glut-1, hazard ratio = 2.427, 95% CI = 5.140, P = 0.021). Retention index had no significant association with DFS or OS. On the Kaplan–Meier survival curves, the patients with high ESUVmax, DSUVmax, cSUVmax and Glut-1 showed significantly worse prognosis than those with low values (ESUVmax: DFS, P = 0.001, OS, P = 0.003; DSUVmax: DFS, P = 0.002, OS, P = 0.004; cSUVmax: DFS, P < 0.001, OS, P = 0.013; Glut-1: DFS, P = 0.012, OS, P = 0.002).

Conclusions
cSUVmax, ESUVmax, DSUVmax and Glut-1 may be more useful biomarkers than retention index for predicting outcomes in NSCLC patients.
Leveraging Interprofessional Team-Based Care Toward Case Management Excellence
Authors: Fink-Samnick Ellen 
Published: November 2019

Health care teams are constructive and efficient ways to approach, assess, coordinate, plan, and facilitate the client-centric and population-based care. Some iteration of team is in place across most practice settings, comprising different professionals and specialists, from multidisciplinary, interdisciplinary, and transdisciplinary to the most recent interprofessional model. This 2-part article series sets the tone for how interprofessional team-based care (IPTBC) empowers the care process. Part 1 focused on the history and fundamental concepts of interprofessional models, with outcomes to promote the value proposition for IPTBC implementation.
This Part 2 article focuses on the identification of seminal group development and team processes. An original model, the Interprofessional Team Activation Cycle (ITAC), is presented, as well as defined tactics for professional case managers to promote successful implementation of IPTBC in their organizations.

Purpose/Objectives:

This article:
Identifies deterrents to implementing IPTBC;Explores timely and successful IPTBC models across the industry;Discusses models of group and team development;Explores the ITAC for professional case management; andIdentifies 10 tactics for case managers to sustain successful IPTBC.

Primary Practice Setting(s):
Applicable to all health and behavioral health settings where case management is practiced.

Findings/Conclusions:
Shifts in reimbursement models, organizational cultures, and client populations have yielded emphasis on the swift IPTBC implementation. In addition, the recognition of team development as a fluid process endemic to achieve client-centric outcomes and organizational return on investment mandates a keen eye to the phases of a team implementation, especially those that are interprofessional in scope.

Implications for Case Management Practice:
With case management so closely linked to the fiscal imperatives of organizations, engagement in IPTBC is a necessity for every practice setting yet not always implemented properly or successfully. Poor team collaboration contributes to unsuccessful outcomes for clients, increased costs, and concerning quality and risk management issues for the organization. Models focused on group development serve to support how health and behavioral health organizations consider and implement interprofessional teams.
BCL-2 Inhibitors, Present and Future
Authors: Ryan Christine E. , Davids Matthew S. 
Published: November 2019

Abstract
The members of the B-cell leukemia/lymphoma-2 (BCL-2) family of proteins are key regulators of the intrinsic apoptotic pathway; dysregulation of this pathway leads to pathologic survival of cancer cells. B-cell leukemia/lymphoma-2 had long been viewed as a promising target for the treatment of several hematologic malignancies, specifically chronic lymphocytic leukemia (CLL), yet for many years the development of a drug to successfully target this protein remained elusive. The approval of the BCL-2 inhibitor venetoclax for relapsed/refractory del(17p) CLL in 2016 represented the culmination of decades of molecular and clinical research and has paved the way for new combination therapy regimens in CLL, including the venetoclax + rituximab regimen approved for relapsed/refractory CLL in 2018 and the venetoclax + obinutuzumab regimen approved for frontline CLL treatment in 2019. Here, we provide an overview of the mechanism of action of BCL-2 inhibition, the role of this approach in the current treatment paradigm of CLL, and an in-depth focus on the clinical trials in CLL involving venetoclax. Additionally, we review key areas of active research including the integration of minimal residual disease as a marker of clinical efficacy in current clinical trials as well as the emergence of venetoclax resistance mechanisms and potential strategies to overcome this resistance. Given the success of venetoclax in the clinical setting thus far, it is likely that BCL-2 inhibition will take on an increasingly important role in the treatment of CLL going forward.
Rasch Analysis of the Patient and Observer Scar Assessment Scale in Linear Scars: Suggestions for a Patient and Observer Scar Assessment Scale v2.1
Authors: Franchignoni Franco , Giordano Andrea , Vercelli Stefano , Bravini Elisabetta , Stissi Valeria , Ferriero Giorgio 
Published: November 2019

Background:
The Patient and Observer Scar Assessment Scale (POSAS) v2.0 is a widely used instrument to evaluate postsurgical scars. Its two subscales respectively investigate the patient’s and clinician’s opinion on the scar quality. However, psychometric studies of the POSAS have indicated that its metric performance is suboptimal, and structural adjustments may be appropriate. The authors aimed to verify through Rasch analysis the measurement properties of the POSAS v2.0, and propose eventual structural refinements for an easier and more confident use of the scale in clinical practice and research.

Methods:
Consecutive patients admitted to two rehabilitation centers for postsurgery rehabilitation over a 2-year period underwent scar assessments with the POSAS v2.0. We performed Rasch analysis to examine the scale’s dimensionality, rating categories, item fit, reliability indices, local item independence, and differential item functioning.

Results:
The study population consisted of 115 patients. The 10 response options of the POSAS showed malfunctioning, and thus were collapsed, forming a parsimonious five-level rating scale, which helped to improve the measurement accuracy. After that, unidimensionality of both subscales was confirmed. Then, internal construct validity of the POSAS v2.0 was demonstrated (through item fit to the Rasch model). Reliability indices were high (≥0.80). No significant differential item functioning was detected concerning age or sex.

Conclusion:
This study demonstrates the good psychometric properties of a simplified Rasch-based version of the Patient and Observer Scar Assessment Scale with five response options (POSAS v2.1) in patients with postsurgical linear scars, and provides insights for future refinement of the tool.
Activated PD-1+ CD4+ T cells represent a short-lived part of the viral reservoir and predict poor immunologic recovery upon initiation of ART
Authors: Eller Michael A. , Hong Ting , Creegan Matthew , Nau Martin E. , Sanders-Buell Eric , Slike Bonnie M. , Krebs Shelly J. , Ratto-Kim Silvia , McElrath M. Juliana , Katabira Elly T. , Bolton Diane L. , Michael Nelson L. , Robb Merlin L. , Tovanabutra Sodsai , Baeten Jared M. , Sandberg Johan K. 
Published: November 2019

Objective:
Activated (CD38+HLA-DR+) PD-1+ CD4+ T cells are strongly associated with virus replication and disease progression in untreated HIV-1 infection, and viral persistence in individuals on ART. Few studies have examined cell-associated viral load (CAVL) in different activated CD4+ T-cell populations to measure relative contributions to viral reservoirs.

Design:
Longitudinal assessment of HIV-1 chronically infected Ugandans initiating ART, to investigate activated CD4+ T-cell populations and their contribution to viral reservoirs.

Methods:
We followed 32 HIV-1 chronically infected individuals from Kampala, Uganda, and determined their CD4+ T-cell counts and viral load at baseline, 6, and 12 months after the initiation of ART. T-cell populations were sorted based on activation profiles and gag DNA was measured to determine CAVL within these populations. Soluble factors associated with inflammation were measured in plasma using a multiplexed platform.

Results:
Concomitant with viral load decline and CD4+ T-cell count rebound, the activated PD-1+ CD4+ T-cell population contracted upon initiation of ART. Baseline levels of activated PD-1+ CD4+ T cells correlated with plasma levels of IP-10 and TNFRII. Interestingly, a higher baseline level of activated PD-1+ CD4+ T cells was associated with poorer CD4+ T-cell recovery after 12 months of ART. This population contributed significantly to the cell-associated HIV DNA load at baseline, whereas their contribution declined on ART, indicating high turnover.

Conclusion:
Activated PD-1+ CD4+ T cells are predictors of poor immunologic recovery on ART and may represent a short-lived component of HIV-1 reservoirs.
Using Implementation Science to Better Integrate Novel Long-Acting Injectable Therapy Into Routine HIV Care
Authors: Czarnogorski Maggie 
Published: November 2019

Background:
The key to maximizing the value of implementation science data is to get the learnings early. A critical contributor to early clinical research data is the biopharmaceutical industry. In partnership with the implementation research community, industry has an opportunity to play a major role to increase the value of implementation research data through earlier integration of implementation questions in the development continuum.

Methods:
This article suggests that by using more hybrid implementation-effectiveness study designs in phase III trials, researchers can accelerate the availability of implementation data closer to the initial introduction of novel treatments into community settings. The biopharmaceutical industry is uniquely poised to lead or collaborate on these trials.

Results:
The first LAI HIV medications are being studied for both HIV prevention and treatment. This paradigm shift in the provision of HIV care is an opportunity to blend implementation research into clinical trials earlier so that the public health community is armed with tested implementation strategies to maximize access and impact when these new medications become available. CUSTOMIZE, a novel phase IIIB—hybrid III implementation-effectiveness trial—is the first-of-its-kind study to examine different implementation strategies to overcome challenges of delivering a LAI antiretroviral medication in various types of HIV clinical settings the US health care system.

Conclusions:
Industry can play a complimentary and additive role by partnering with implementation science researchers to understand the implementation strategies sooner in the development pipeline. These collaborations may allow for earlier, more informed, and strategic HIV public health programs in the future.
Surgical Management of Complex Syndromic Craniosynostosis: Experience With a Rare Genetic Variant
Authors: Celie Karel-Bart , Yuan Melissa , Hoffman Caitlin , O’Connor Ashley , Bogue Jarrod , Imahiyerobo Thomas 
Published: November 2019

Abstract
Patients with syndromic craniosynostosis (CS) can present with both intracranial and extracranial manifestations. Extracranial features include proptosis, exorbitism, and midface hypoplasia. Intracranial manifestations can include elevated intracranial pressure (ICP), brainstem compression, foramen magnum stenosis or jugular foramen hypoplasia with resultant venous hypertension and anomalous drainage. While fronto-orbital advancement, cranial vault remodeling, and posterior fossa decompression are standard surgical approaches to normalizing orbito-cranial volume and morphology, associated hydrocephalus, anomalous venous drainage, and tonsillar herniation often affect the timing, safety, and selection of corrective interventions. The surgical decision-making to circumvent venous emissaries, effectively time treatment of hydrocephalus, and address posterior versus anterior pathology primarily has not been widely described in the literature, and is important in the development of guidelines in these complex cases. In this report, we describe the surgical management of a patient with Jackson-Weiss syndrome presenting with delayed, but rapidly progressive bilateral lambdoid CS, severe proptosis, midface hypoplasia, elevated ICP, hydrocephalus, tonsillar ectopia, and severe venous hypertension with anomalous drainage. We review the literature related to management of complex synostosis and present our surgical decision-making in the setting of complex syndromic synostosis to aid in the formation of guidelines toward approaching these cases.
A screening platform based on epitope editing for drug discovery
Authors: Zhu Biyue , Yang Jing , Van Richard , Ran Kathleen , Yin Keyi , Liang Yingxia , Shen Xunuo , Yin Wei , Choi Se Hoon , Lu Ying , Wang Changning , Shao Yihan , Tanzi Rudolph E. , Zhang Can , Cheng Yan , Zhang Zhirong , Ran Chongzhao 
Published: November 2019

AbstractThe interaction between an antibody and its epitope has been daily utilized in various biological studies; however it has been rarely explored whether small molecules can alter the interaction. We discovered that small molecules could alter/edit surface properties of amyloid beta (Aβ) epitopes, and consequently inhibit or enhance corresponding antibody recognition. Remarkably, this editing effect could generate functional changes including protein aggregation behaviors, cell cytokine secreting and in vivo microglia activation. According to this discovery, we proposed ascreenplatform based onepitopeediting fordrug discovery (SPEED). With a small library of compounds, we validated that SPEED could be used to seek new leads for Aβ species. We also demonstrated that this platform could potentially be extended to other targets including tau protein and PD-L1 protein. The SPEED is a simple, fast and label-free screening method. We believe that the SPEED strategy could be universally applicable for seeking and validating drug candidates and imaging ligands.
Drivers of phyllosphere microbial functional diversity in a neotropical forest
Authors: Lajoie Geneviève , Maglione Rémi , Kembel Steven W. 
Published: November 2019

AbstractBackgroundThe phyllosphere is an important microbial habitat but our understanding of how plant hosts drive the composition of their associated leaf microbial communities and whether taxonomic associations between plants and phyllosphere microbes represent adaptive matching remains limited. In this study we quantify bacterial functional diversity in the phyllosphere of 17 tree species in a diverse neotropical forest using metagenomic shotgun sequencing. We ask how hosts drive the functional composition of phyllosphere communities and their turnover across tree species, using host functional traits and phylogeny. We compare functional predictions inferred from 16S gene sequencing with functions estimated from metagenomic shotgun sequencing.ResultsNeotropical tree phyllosphere communities are dominated by functions related to the metabolism of carbohydrates, amino acids and energy acquisition, along with environmental signalling pathways involved in membrane transport. While most functional variation was observed within communities, there is non-random assembly of microbial functions across host species possessing different leaf traits. Metabolic functions related to biosynthesis and degradation of secondary compounds, along with signal transduction and cell-cell adhesion were particularly important in driving the match between microbial functions and host traits. These microbial functions were also evolutionarily conserved across the host phylogeny. Functional predictions inferred from 16S gene sequences were weakly correlated with functional annotations from the same samples through metagenomic shotgun sequencing, especially for finer-scale functional annotations.ConclusionsFunctional profiling based on metagenomic shotgun sequencing offers evidence for the presence of a core functional microbiome across phyllosphere communities of neotropical trees. While functional turnover across phyllosphere communities is relatively small, the association between microbial functions and leaf trait gradients among host species supports a significant role for plant hosts as selective filters on phyllosphere community assembly. This interpretation is supported by the presence of phylogenetic signal for the microbial traits driving inter-community variation across the host phylogeny. Our comparison of functional annotations derived from 16S genes versus metagenomic shotgun sequencing suggests caution in using functions inferred from 16S genes for studying ecological dynamics in phyllosphere communities. Taken together, our results suggest that there is adaptive matching between phyllosphere microbes and their plant hosts.
A classification of functional pitcher types in Nepenthes (Nepenthaceae)
Authors: Cheek Martin , Jebb Matthew , Murphy Bruce 
Published: November 2019

AbstractWe classify Nepenthes species into 12 functional pitcher types, based on combinations of traits that appear to comprise different syndromes for capturing nutrients, usually from animals. For nine of these types the trapping syndromes are already documented, six targeting live animals (hence carnivorous), and three targeting other nutrient sources (non-carnivorous). Yet, for three pitcher types here is no previous documentation of the syndrome and we do not yet know what sources of nutrients are being targeted. Mapping all these pitcher types on the latest, near comprehensive species-level phylogenomic tree of Nepenthes (Murphy et al. 2019) shows that apart from the ancestral pitcher type 1, most of the remaining pitcher types have evolved independently, in different parts of the phylogenetic tree, usually in several different places. Each of the 12 pitcher types is characterised morphologically and illustrated, its trapping syndrome discussed, and example species are given. An identification key to the 12 pitcher types is presented. The possibility of additional pitcher types being present is discussed.
The host antiviral ribonuclease L protein supports Zika virus replication factory formation to enhance infectious virus production
Authors: Whelan Jillian N , Hatterschide Joshua , Renner David M. , Dong Beihua , Silverman Robert H , Weiss Susan R 
Published: November 2019

SummaryThe flavivirus Zika virus (ZIKV) activates ribonuclease L (RNase L) catalytic antiviral function during infection, yet deletion of RNase L decreases ZIKV production, suggesting a proviral role of RNase L. In this study, we reveal that latent RNase L supports ZIKV replication factory (RF) assembly. Deletion of RNase L induced broader cellular distribution of ZIKV dsRNA and NS3 compared with densely concentrated RFs detected in WT cells. An inactive form of RNase L was sufficient to contain ZIKV genome and dsRNA within a smaller area, which increased levels of viral RNA within RFs as well as infectious ZIKV released from the cell. We used a microtubule stabilization drug to demonstrate that RNase L deletion impaired the cytoskeleton rearrangements that are required for proper generation of RFs. During infection with dengue or West Nile Kunjin viruses, RNase L decreased virus production, suggesting that RNase L proviral function is specific to ZIKV.
Glyoxylic acid overcomes 1-MCP-induced blockage of fruit ripening in Pyrus communis L. var. ‘D’Anjou’
Authors: Hewitt Seanna Louise , Dhingra Amit 
Published: November 2019

Abstract1-methylcyclopropene (1-MCP) in an ethylene receptor antagonist which blocks ethylene perception and downstream ripening responses in climacteric fruit imparting a longer shelf life. However, in European pear, application of 1-MCP irreversibly obstructs the onset of system 2 ethylene production resulting in perpetually unripe fruit with undesirable quality. Application of exogenous ethylene, carbon dioxide and treatment to high temperatures is not able to reverse the blockage in ripening. We recently reported that during cold conditioning, activation of AOX occurs pre-climaterically. In this study we report that activation of AOX via exposure of 1-MCP treated ‘D’Anjou’ pear fruit to glyoxylic acid triggers an accelerated ripening response. Ripening is consistently evident in decrease of fruit firmness and onset of S1-S2 ethylene transition. Time course ripening related measurements and transcriptomic analysis were performed to assess the effects of glyoxylic acid-driven stimulation of ripening. Transcriptomic and functional enrichment analyses revealed genes and ontologies implicated in glyoxylic acid mediated ripening, including alternative oxidase, TCA cycle, fatty acid metabolism, amino acid metabolism, organic acid metabolism, and ethylene responsive pathways. These observations implicate the glyoxylate cycle as a metabolic hub linking multiple pathways to stimulate ripening through an alternate mechanism. The results provide information regarding how blockage caused by 1-MCP may be circumvented at the metabolic level, thus opening avenues for consistent ripening in pear and possibly other fruit.