bluuebunny/crossref_metadata_2025_split huggingface dataset:
An iterative method for classification of binary data
Authors: Molitor Denali , Needell Deanna 
Published: February 2020

AbstractIn today’s data-driven world, storing, processing and gleaning insights from large-scale data are major challenges. Data compression is often required in order to store large amounts of high-dimensional data, and thus, efficient inference methods for analyzing compressed data are necessary. Building on a recently designed simple framework for classification using binary data, we demonstrate that one can improve classification accuracy of this approach through iterative applications whose output serves as input to the next application. As a side consequence, we show that the original framework can be used as a data preprocessing step to improve the performance of other methods, such as support vector machines. For several simple settings, we showcase the ability to obtain theoretical guarantees for the accuracy of the iterative classification method. The simplicity of the underlying classification framework makes it amenable to theoretical analysis.
Gene regulatory networks associated with lateral root and nodule development in soybean
Authors: Smita Shuchi , Kiehne Jason , Adhikari Sajag , Zeng Erliang , Ma Qin , Subramanian Senthil 
Published: February 2020

AbstractLegume plants such as soybean produce two major types of root lateral organs, lateral roots and root nodules. A robust computational framework was developed to predict potential gene regulatory networks (GRNs) associated with root lateral organ development in soybean. A genome-scale expression data set was obtained from soybean root nodules and lateral roots and subjected to biclustering using QUBIC (QUalitative BIClustering algorithm). Biclusters and transcription factor (TF) genes with enriched expression in lateral root tissues were converged using different network inference algorithms to predict high-confidence regulatory modules that were repeatedly retrieved in different methods. The ranked combination of results from all different network inference algorithms into one ensemble solution identified 21 GRN modules of 182 co-regulated genes networks, potentially involved in root lateral organ development stages in soybean. The workflow correctly predicted previously known nodule- and lateral root-associated TFs including the expected hierarchical relationships. The results revealed distinct high-confidence GRN modules associated with early nodule development involving AP2, GRF5 and C3H family TFs, and those associated with nodule maturation involving GRAS, LBD41 and ARR18 family TFs. Knowledge from this work supported by experimental validation in the future is expected to help determine key gene targets for biotechnological strategies to optimize nodule formation and enhance nitrogen fixation.
Adult dogs of different breed sizes have similar threonine requirements as determined by the indicator amino acid oxidation technique
Authors: Mansilla Wilfredo D , Fortener Lisa , Templeman James R , Shoveller Anna K 
Published: February 2020

Abstract
Threonine (Thr) requirements for immature (growing) Beagles have been determined, but little knowledge is available on Thr requirements for maintenance in mature dogs. Moreover, differences of Thr requirements among different breeds or sizes of adult dogs have not been investigated. The objective of the present study was to determine Thr requirements in adult dogs of three different breeds using the indicator amino acid oxidation (IAAO) technique. In total, 13 adult dogs were used, 4 Miniature Dachshunds (5.8 ± 0.4 kg body weight [BW]; 3 spayed and 1 neutered), 4 spayed Beagles (9.3 ± 0.6 kg BW), and 5 neutered Labrador Retrievers (30.5 ± 1.7 kg BW). Dogs were fed a Thr-deficient diet (Thr = 0.23%) and randomly allocated to receiving one of seven concentrations of Thr supplementation (final Thr concentration in experimental diets was 0.23%, 0.33%, 0.43%, 0.53%, 0.63%, 0.73%, and 0.83%; as fed basis) for 2 d. After 2 d of adaptation to the experimental diets, dogs underwent individual IAAO studies. During the IAAO studies, total daily feed was divided into 13 equal meals; at the sixth meal, dogs were fed a bolus of l-[1-13C]-Phenylalanine (Phe) (9.40 mg/kg BW), and thereafter, l-[1-13C]-Phe (2.4 mg/kg BW) was supplied with every meal. Before feeding the next experimental diet, dogs were fed a Thr-adequate basal diet for 4 d (Thr = 0.80% as fed basis) in known amounts that maintained individual dog BW. Total production of 13CO2 during isotopic steady state was determined by enrichment of 13CO2 in breath samples and total production of CO2 measured using indirect calorimetry. The mean requirements for Thr, defined as the breakpoint, and the 95% confidence interval (CI) were determined using a two-phase linear regression model. For Miniature Dachshunds, the two-phase model was not significant, and Thr requirements could not be determined. Mean Thr requirements for Beagles and Labradors were 72.2 and 64.1 mg/kg BW on an as-fed basis, respectively. The requirement for Thr between these two dog breeds was not different (P &gt; 0.10). Thus, the data for Beagles and Labradors were pooled and a mean requirement for Thr was determined at 66.9 mg/kg BW, and the 95% CI was estimated at 84.3 mg/kg BW. In conclusion, estimated Thr requirements for Beagles and Labradors did not differ, and these recommendations are higher than those suggested by NRC (2006) and AAFCO (2014) for adult dogs at maintenance.
Stirring rate affects thermodynamics and unfolding kinetics in isothermal titration calorimetry
Authors: Maruno Takahiro , Ohkubo Tadayasu , Uchiyama Susumu 
Published: February 2020

Abstract
Isothermal titration calorimetry (ITC) directly provides thermodynamic parameters depicting the energetics of intermolecular interactions in solution. During ITC experiments, a titration syringe with a paddle is continuously rotating to promote a homogeneous mixing. Here, we clarified that the shape of the paddles (flat, corkscrew and small-pitched corkscrew) and the stirring rates influence on the thermodynamic parameters of protein–ligand interaction. Stirring with the flat paddle at lower and higher rate both yielded a lower exothermic heat due to different reasons. The complete reaction with no incompetent fractions was achieved only when the stirring was performed at 500 or 750 rpm using the small-pitched corkscrew paddle. The evaluation of the protein solution after 1,500 rpm stirring indicated that proteins in the soluble fraction decreased to 94% of the initial amount, among which 6% was at an unfolded state. In addition, a significant increase of micron aggregates was confirmed. Furthermore, a new approach for the determination of the unfolding kinetics based on the time dependence of the total reaction heat was developed. This study demonstrates that a proper stirring rate and paddle shape are essential for the reliable estimation of thermodynamic parameters in ITC experiments.
Tales of the city: what do agglomeration cases tell us about agglomeration in general?
Authors: Faggio Giulia , Silva Olmo , Strange William C 
Published: February 2020

AbstractThis article considers the heterogeneous microfoundations of agglomeration economies. It studies the co-location of industries to look for evidence of labour pooling, input sharing and knowledge spillovers. The novel contribution of the article is that it estimates single-industry models using a common empirical framework that exploits the cross-sectional variation in how one industry co-locates with the other industries in the economy. This unified approach yields evidence on the relative importance of the Marshallian microfoundations at the single-industry level, allowing for like-for-like cross-industry comparisons on the determinants of agglomeration. Using UK data, we estimate such microfoundation models for 97 manufacturing sectors, including the classic agglomeration cases of automobiles, computers, cutlery and textiles. These four cases—as with all of the individual industry models we estimate—clearly show the importance of the Marshallian forces. However, they also highlight how the importance of these forces varies across industries—implying that extrapolation from cases should be viewed with caution. The article concludes with an investigation of the pattern of heterogeneity. The degree of an industry’s clustering (localisation), entrepreneurship, incumbent firm size and worker education are shown to contribute to the pattern of heterogeneous microfoundations.
Genetic Counseling and Germline Testing in the Era of Tumor Sequencing: A Cohort Study
Authors: Klek Stefan , Heald Brandie , Milinovich Alex , Ni Ying , Abraham Jame , Mahdi Haider , Estfan Bassam , Khorana Alok A , Bolwell Brian J , Grivas Petros , Sohal Davendra P S , Funchain Pauline 
Published: February 2020

Abstract

Background
The clinical impact of addressing potential germline alterations from tumor-only next-generation sequencing (NGS) is not well characterized. Current guidelines for cancer genetic testing may miss clinically actionable germline changes, which may have important implications for cancer screening, treatment, and prevention. We examined whether increasing involvement of the clinical genetics service during somatic tumor-only NGS review at Molecular Tumor Board (MTB) increases the detection of germline findings.

Methods
In a retrospective evaluation of patients who underwent tumor-only NGS and were reviewed at MTB, we quantified genetic counseling (GC) referrals as well as germline testing uptake and results across three cohorts: before (C1) and after (C2) the addition of tumor-only NGS review and after (C3) instituting a formal process to coordinate NGS-based genetics referrals to preexisting oncology appointments. All statistical tests were two-sided.

Results
From 2013 to 2017, 907 tumor-only NGS reports were reviewed at MTB (nC1 = 281, nC2 = 493, nC3 = 133); gastrointestinal (22.5%), lung (19.7%), genitourinary (14.8%), and breast (14.1%) were the most common index cancers. GC visits due to MTB increased with each successive cohort (C1 = 1.1%, C2 = 6.9%, C3 = 13.5%; P for trend [Ptrend] &lt; .001), as did germline testing (C1 = 0.7%, C2 = 3.2%, C3 = 11.3%; Ptrend &lt; .001). Diagnosis of germline pathogenic variants increased with each successive cohort (C1 = 1.4%, C2 = 2.0%, C3 = 7.5%; Ptrend = .003) and with germline pathogenic variants found by MTB review (C1 = 0.4%, C2 = 0.4%, C3 = 2.3%; Ptrend = .12).

Conclusions
Both review of tumor-only NGS by genetics and the institution of a process coordinating GC with oncology appointments increased the discovery of germline pathogenic variants from tumor-only NGS testing. Furthermore, this process identified germline pathogenic variant carriers who would not have otherwise met standard criteria for germline testing.
Family-specific analysis of variant pathogenicity prediction tools
Authors: Zaucha Jan , Heinzinger Michael , Tarnovskaya Svetlana , Rost Burkhard , Frishman Dmitrij 
Published: February 2020

Abstract
Using the presently available datasets of annotated missense variants, we ran a protein family-specific benchmarking of tools for predicting the pathogenicity of single amino acid variants. We find that despite the high overall accuracy of all tested methods, each tool has its Achilles heel, i.e. protein families in which its predictions prove unreliable (expected accuracy does not exceed 51% in any method). As a proof of principle, we show that choosing the optimal tool and pathogenicity threshold at a protein family-individual level allows obtaining reliable predictions in all Pfam domains (accuracy no less than 68%). A functional analysis of the sets of protein domains annotated exclusively by neutral or pathogenic mutations indicates that specific protein functions can be associated with a high or low sensitivity to mutations, respectively. The highly sensitive sets of protein domains are involved in the regulation of transcription and DNA sequence-specific transcription factor binding, while the domains that do not result in disease when mutated are responsible for mediating immune and stress responses. These results suggest that future predictors of pathogenicity and especially variant prioritization tools may benefit from considering functional annotation.
Phase I study of intraventricular infusions of autologous ex vivo expanded NK cells in children with recurrent medulloblastoma and ependymoma
Authors: Khatua Soumen , Cooper Laurence J N , Sandberg David I , Ketonen Leena , Johnson Jason M , Rytting Michael E , Liu Diane D , Meador Heather , Trikha Prashant , Nakkula Robin J , Behbehani Gregory K , Ragoonanan Dristhi , Gupta Sumit , Kotrotsou Aikaterini , Idris Tagwa , Shpall Elizabeth J , Rezvani Katy , Colen Rivka , Zaky Wafik , Lee Dean A , Gopalakrishnan Vidya 
Published: February 2020

AbstractBackgroundRecurrent pediatric medulloblastoma and ependymoma have a grim prognosis. We report a first-in-human, phase I study of intraventricular infusions of ex vivo expanded autologous natural killer (NK) cells in these tumors, with correlative studies.MethodsTwelve patients were enrolled, 9 received protocol therapy up to 3 infusions weekly, in escalating doses from 3 × 106 to 3 × 108 NK cells/m2/infusion, for up to 3 cycles. Cerebrospinal fluid (CSF) was obtained for cellular profile, persistence, and phenotypic analysis of NK cells. Radiomic characterization on pretreatment MRI scans was performed in 7 patients, to develop a non-invasive imaging-based signature.ResultsPrimary objectives of NK cell harvest, expansion, release, and safety of 112 intraventricular infusions of NK cells were achieved in all 9 patients. There were no dose-limiting toxicities. All patients showed progressive disease (PD), except 1 patient showed stable disease for one month at end of study follow-up. Another patient had transient radiographic response of the intraventricular tumor after 5 infusions of NK cell before progressing to PD. At higher dose levels, NK cells increased in the CSF during treatment with repetitive infusions (mean 11.6-fold). Frequent infusions of NK cells resulted in CSF pleocytosis. Radiomic signatures were profiled in 7 patients, evaluating ability to predict upfront radiographic changes, although they did not attain statistical significance.ConclusionsThis study demonstrated feasibility of production and safety of intraventricular infusions of autologous NK cells. These findings support further investigation of locoregional NK cell infusions in children with brain malignancies.
Responses in the diffusivity and vascular function of the irradiated normal brain are seen up until 18 months following SRS of brain metastases
Authors: Nilsen Line Brennhaug , Digernes Ingrid , Grøvik Endre , Saxhaug Cathrine , Latysheva Anna , Geier Oliver , Breivik Birger , Sætre Dag Ottar , Jacobsen Kari Dolven , Helland Åslaug , Emblem Kyrre Eeg 
Published: February 2020

Abstract

Background
MRI may provide insights into longitudinal responses in the diffusivity and vascular function of the irradiated normal-appearing brain following stereotactic radiosurgery (SRS) of brain metastases.

Methods
Forty patients with brain metastases from non-small cell lung cancer (N = 26) and malignant melanoma (N = 14) received SRS (15–25 Gy). Longitudinal MRI was performed pre-SRS and at 3, 6, 9, 12, and 18 months post-SRS. Measures of tissue diffusivity and vascularity were assessed by diffusion-weighted and perfusion MRI, respectively. All maps were normalized to white matter receiving less than 1 Gy. Longitudinal responses were assessed in normal-appearing brain, excluding tumor and edema, in the LowDose (1–10 Gy) and HighDose (&gt;10 Gy) regions. The Eastern Cooperative Oncology Group (ECOG) performance status was recorded pre-SRS.

Results
Following SRS, the diffusivity in the LowDose region increased continuously for 1 year (105.1% ± 6.2%; P &lt; .001), before reversing toward pre-SRS levels at 18 months. Transient reductions in microvascular cerebral blood volume (P &lt; .05), blood flow (P &lt; .05), and vessel densities (P &lt; .05) were observed in LowDose at 6–9 months post-SRS. Correspondingly, vessel calibers in LowDose transiently increased at 3–9 months (P &lt; .01). The responses in HighDose displayed similar trends as in LowDose, but with larger interpatient variations. Vascular responses followed pre-SRS ECOG status.

Conclusions
Our results imply that even low doses of radiation to normal-appearing brain following cerebral SRS induce increased diffusivity and reduced vascular function for up until 18 months. In particular, the vascular responses indicate the reduced ability of the normal-appearing brain tissue to form new capillaries. Assessing the potential long-term neurologic effects of SRS on the normal-appearing brain is warranted.
The Effect of Women’s Descriptive Representation on Premature Mortality
Authors: Patton Dana , Fording Richard C 
Published: February 2020

AbstractAlthough many studies have found that women legislators pursue policies important to women, we know relatively little concerning the effect of women’s descriptive representation (WDR) on women’s quality of life. We address this question by examining the relationship between the election of women state legislators and public health. Specifically, we estimate the effect of WDR on premature death rates from 1982 to 2010. We find that WDR serves to improve the well-being of both women and men. However, the effect of WDR on women’s health is contingent on several important factors. First, the health-improving effects of WDR are most strongly related to the descriptive representation of Democratic women. Second, the effect of Democratic WDR on women’s health, relative to men’s health, increases with the scale of the state’s Medicaid program. Finally, we estimate the mediating role of nine specific policies, finding that four policies mediate the effect of Democratic WDR on premature mortality. Overall, our results suggest that policy remedies aimed at improving the severe underrepresentation of women in government may help to improve the relatively low ranking of the United States on indicators of public health.
In-vitro and in-vivo models for hepatitis B cure research
Authors: Allweiss Lena , Strick-Marchand Helene 
Published: February 2020

Purpose of review
Antiviral therapy for chronic hepatitis B infection is rarely curative, thus research in HBV cure strategies is a priority. Drug development and testing has been hampered by the lack of robust cell culture systems and small animal models. This review summarizes existing models for HBV cure research and focuses on recent developments since 2017 until today.

Recent findings
The field has progressed in the development of cell culture and animal models to study HBV. Although early cell culture systems relied on transfection of HBV genomes in hepatoma cell lines, novel models expressing the entry receptor for HBV are susceptible to infection. Improved culture conditions for primary human hepatocytes, the primary target of HBV, have enabled the screening and validation of novel antivirals. Mouse models grafted with partially humanized livers are suitable for testing viral entry inhibitors or direct acting antivirals, and can be reconstituted with human immune cells to analyze immunotherapies. Other immunocompetent models include mice transduced with HBV genomes or woodchucks infected with their native hepatitis virus.

Summary
Model systems for HBV research have helped lay the groundwork for the development and optimization of antiviral and immune-based therapeutic approaches that are now moving to clinical trials.
The Discrepancy Between Cognitive Complaints and Neuropsychological Test Findings in Persons With Traumatic Brain Injury
Authors: Vos Leia , Williams Michael W. , Poritz Julia M. P. , Ngan Esther , Leon-Novelo Luis , Sherer Mark 
Published: February 2020

Objective:
To better identify variables related to discrepancies between subjective cognitive complaints and objective neuropsychological findings in persons with traumatic brain injury (TBI).

Setting:
Three rehabilitation centers in the United States.

Participants:
In total, 504 community-dwelling adult survivors of TBI following discharge from inpatient rehabilitation.

Design:
Prospective cohort observation study.

Main Measures:
Wechsler Adult Intelligence Scale, Fourth Edition, Digit Span; Rey Auditory Verbal Learning Test; Trail Making Test, Part B; Word Memory Test; Patient Health Questionnaire-9; Neurobehavioral Symptom Inventory; TBI-Quality of Life item bank.

Results:
Statistical analyses revealed multiple factors associated with subjective-objective discrepancies in attention, memory, and executive functions. Depression was consistently associated with underestimation of cognitive abilities. However, subjective-objective discrepancies varied by cognitive domains in regard to other factors related to underestimation and overestimation of abilities.

Conclusions:
Reconciling and interpreting subjective-objective discrepancies regarding cognitive functions following TBI are important tasks for case conceptualization and treatment planning. Depression is an important patient characteristic to consider when discrepancy patterns indicate underestimation of cognitive abilities. This study highlights the importance of assessing mood, a modifiable patient characteristic, with self-report symptom inventories. Future studies are needed to connect these findings with TBI outcomes.
Receipt of Treatment for Depression Following Traumatic Brain Injury
Authors: Albrecht Jennifer S. , Abariga Samuel A. , dosReis Susan , Perfetto Eleanor M. , Mullins C. Daniel , Rao Vani 
Published: February 2020

Objective:
Lack of evidence for efficacy and safety of treatment and limited clinical guidance have increased potential for undertreatment of depression following traumatic brain injury (TBI).

Methods:
We conducted a retrospective cohort study among individuals newly diagnosed with depression from 2008 to 2014 to assess the impact of TBI on receipt of treatment for incident depression using administrative claims data. We created inverse probability of treatment-weighted populations to evaluate the impact of TBI on time to receipt of antidepressants or psychotherapy following new depression diagnosis during 24 months post-TBI or matched index date (non-TBI cohort).

Results:
Of 10 428 individuals with incident depression in the TBI cohort, 44.7% received 1 or more antidepressants and 20.0% received 1 or more psychotherapy visits. Of 10 463 in the non-TBI cohort, 41.2% received 1 or more antidepressants and 17.6% received 1 or more psychotherapy visits. TBI was associated with longer time to receipt of antidepressants compared with the non-TBI cohort (average 39.6 days longer than the average 126.2 days in the non-TBI cohort; 95% confidence interval [CI], 24.6-54.7). Longer time to psychotherapy was also observed among individuals with TBI at 6 months post-TBI (average 17.1 days longer than the average 47.9 days in the non-TBI cohort; 95% CI, 4.2-30.0), although this association was not significant at 12 and 24 months post-TBI.

Conclusions:
This study raises concerns about the management of depression following TBI.