bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congressional nominations and party emergence, 1788–1808
Authors: Gooch Aric Dale , Dow Jay 
Published: September 2021

AbstractObjectiveWe study the development of nomination procedures for congressional elections by the Democratic‐Republican and Federalist parties in the first party era (1788–1808).MethodsOur study rests on primary source evidence from congressional elections contested in Pennsylvania, New Hampshire, Massachusetts, and New Jersey.ResultsWe demonstrate that in these states, party nominations drew popular involvement, a wide pool of potential nominees, selected among them according to well‐understood rules and norms, and subsequently focused electoral supporters on the nominated candidates.ConclusionThe existence of structured nominations has significant implications for U.S. party development. Most importantly, it suggests the Democratic‐Republican and Federalist parties were more institutionalized than previously thought. To the extent that organization capacity is a key marker in party development, this suggests that the early American parties were more developed than is generally recognized.
Diagnostic significance of IgG and albumin indices versus oligoclonal band types in demyelinating disorders
Authors: Belimezi Maria , Kalliaropoulos Antonios , Mentis Alexios-Fotios A , Chrousos George P 
Published: September 2021

AimsThe laboratory diagnosis of demyelinating inflammatory disorders (DIDs) relies on both intrathecal oligoclonal band (OCB) positivity and IgG index. Although OCB typing remains the gold-standard test for DIDs, it can be laborious and ambiguous, complicating diagnostics, and unduly increasing diagnostic time. We examined whether serum or cerebrospinal fluid (CSF) parameters can classify OCB types and, thus, be used as a replacement test to standard OCB typing.MethodsWe retrospectively analysed >1000 prospectively collected samples of patients with DIDs and quantified albumin and IgG levels in the CSF and serum. We determined OCB types by isoelectric focusing combined with immunofixation and evaluated the diagnostic accuracies of IgG and albumin indices in discriminating OCB types by receiver operating characteristic curves and multinomial regression.ResultsAn IgG index cut-off of 0.589 differentiated types 2/3 from types 1/4 (area under the curve 0.780, 95% CI 0.761 to 0.812, p<0.001; specificity: 71.10%, sensitivity: 73.45%). Albumin quotient cut-off values of 6.625 and of 6.707 discriminated type 1 from type 4 and type 2 from type 3, respectively (specificity: <55%, sensitivity: <75%). Female sex, age, IgG index, CSF IgG and serum albumin were associated with different OCB types.ConclusionsOur study reveals that IgG and albumin index can differentiate OCB types with adequate accuracy, especially if refined by age and gender.
Effects of the Brazilian tax reform plans on the tobacco market
Authors: Divino Jose Angelo , Ehrl Philipp , Candido Osvaldo , Valadao Marcos Aurelio Pereira 
Published: September 2021

BackgroundThere has been an intense debate in the Brazilian National Congress on how to reform the country’s tax system on consumption. This paper investigates the effects of the tax reform under the Constitutional Amendment Bill 45/2019 on cigarette prices, consumption and tax collection. The reform will introduce a new goods and services tax (GST) and tobacco excise tax (TET).MethodsThe micro data from the National Household Sample Survey (PNAD) of 2008 and the National Health Survey (PNS) of 2013 are inputs in the simulation in order to determine the smoking behaviour and consumer responses to price changes as accurately as possible across the different Brazilian states. We developed three scenarios for the tobacco tax reform and their effects on cigarette prices, smoking behaviour and tax collection. We also estimate the size of the illicit cigarette market by Brazilian state and simulate the impacts of a 10% reduction in its market share.FindingsOverall, we found that a GST of 27% and a TET of either 51%, 56% or specific 3.89 BRL per pack would lead to considerably higher cigarette prices, lower cigarette consumption and, above all, an increase of cigarette tax collection between 8% and 27% depending on the state. A discretionary 10% reduction in the illicit market would add about 8.5% of extra tax collection per year to the country.ConclusionsThe simulated scenarios demonstrated that, to keep the cigarette prices at least at the same level as those in the current tax scheme, TET should be no less than 77.85% of the retail price. This means that any politically feasible tax reform should result in higher cigarette prices and a reduction in cigarette consumption. Considering the nationwide effect, in all scenarios, the total increase in tobacco tax revenue is around 8.5% or 1.5 billion BRL per year. This extra revenue is highly desirable in an environment of chronic fiscal imbalance and the COVID-19 pandemic crisis.
Approaches and research needs for advancing the protection and recovery of imperilled freshwater fishes and mussels in Canada1
Authors: Castañeda Rowshyra A. , Ackerman Josef D. , Chapman Lauren J. , Cooke Steven J. , Cuddington Kim , Dextrase Alan J. , Jackson Donald A. , Koops Marten A. , Krkošek Martin , Loftus Kevin K. , Mandrak Nicholas E. , Martel André L. , Molnár Péter K. , Morris Todd J. , Pitcher Trevor E. , Poesch Mark S. , Power Michael , Pratt Thomas C. , Reid Scott M. , Rodríguez Marco A. , Rosenfeld Jordan , Wilson Chris C. , Zanatta David T. , Drake D. Andrew R. 
Published: September 2021

Effective conservation requires that species recovery measures are informed by rigorous scientific research. For imperilled freshwater fishes and mussels in Canada, numerous research gaps exist, in part owing to the need for specialized research methods. The Canadian Freshwater Species at Risk Research Network (SARNET) was formed and identified or implemented approaches to address current research gaps, including (1) captive experimental research populations, (2) nonlethal methods for estimating abundance and distribution, (3) nonlethal field methods to measure life-history parameters, (4) species distribution models informed by co-occurring species, (5) conservation physiology to inform habitat and threat science, (6) evidence syntheses to evaluate threats and recovery measures, (7) disease-transmission models to understand mussel–host relationships, (8) experimental mesocosms and manipulative experiments to evaluate key habitat stressors, (9) threat and hazard models for predictive applications, and (10) rigorous evaluation of surrogate species. Over a dozen threat- and recovery-focused SARNET research applications are summarized, demonstrating the value of a coordinated research program between academics and government to advance scientific research on, and to support the recovery of, imperilled freshwater species.
The plasticity of nerve fibers: the prolonged effects of polarization of afferent fibers
Authors: Jankowska Elzbieta , Hammar Ingela 
Published: September 2021

The review surveys various aspects of the plasticity of nerve fibers, in particular the prolonged increase in their excitability evoked by polarization, focusing on a long-lasting increase in the excitability of myelinated afferent fibers traversing the dorsal columns of the spinal cord. We review the evidence that increased axonal excitability 1) follows epidurally applied direct current (DC) as well as relatively short (5 or 10 ms) current pulses and synaptically evoked intrinsic field potentials; 2) critically depends on the polarization of branching regions of afferent fibers at the sites where they bifurcate and give off axon collaterals entering the spinal gray matter in conjunction with actions of extrasynaptic GABAA membrane receptors; and 3) shares the feature of being activity-independent with the short-lasting effects of polarization of peripheral nerve fibers. A comparison between the polarization evoked sustained increase in the excitability of dorsal column fibers and spinal motoneurons (plateau potentials) indicates the possibility that they are mediated by partly similar membrane channels (including noninactivating type L Cav++ 1.3 but not Na+ channels) and partly different mechanisms. We finally consider under which conditions transspinally applied DC (tsDCS) might reproduce the effects of epidural polarization on dorsal column fibers and the possible advantages of increased excitability of afferent fibers for the rehabilitation of motor and sensory functions after spinal cord injuries. NEW & NOTEWORTHY This review supplements previous reviews of properties of nerve fibers by surveying recent experimental evidence for their long-term plasticity. It also extends recent descriptions of spinal effects of DC by reviewing effects of polarization of afferent nerve fibers within the dorsal columns, the mechanisms most likely underlying the long-lasting increase in their excitability and possible clinical implications.
Determination of Position Resolution for LYSO Scintillation Crystals Using Geant4 Monte Carlo Code
Authors: Yahya M. F. O. , Kocak F. 
Published: September 2021

LYSO scintillation crystals, due to their significant characteristics such as high light yield, fast decay time, small Moliére radius, and good radiation hardness, are proposed to be used for the electromagnetic calorimeter section of the Turkish Accelerator Center Particle Factory (TAC-PF) detector. In this work, the center of gravity technique was used to determine the impact coordinates of an electron initiating an electromagnetic shower in a LYSO array, in a calorimeter module containing nine crystals, each

25

mm
×
25

mm

in cross-section and 200 mm in length. The response of the calorimeter module has been studied with electrons having energies in the range 0.1 GeV-2 GeV. By using the Monte Carlo simulation based on Geant4, the two-dimensional position resolution of the module is obtained as

σ

R

mm

=

3.95
±
0.08

/

E

⊕

1.91
±
0.11

at the center of the crystal.
Functional Impact of Genomic Complexity on the Transcriptome of Multiple Myeloma
Authors: Ziccheddu Bachisio , Da Vià Matteo C. , Lionetti Marta , Maeda Akihiro , Morlupi Silvia , Dugo Matteo , Todoerti Katia , Oliva Stefania , D'Agostino Mattia , Corradini Paolo , Landgren Ola , Iorio Francesco , Pettine Loredana , Pompa Alessandra , Manzoni Martina , Baldini Luca , Neri Antonino , Maura Francesco , Bolli Niccolò 
Published: September 2021

Abstract

Purpose:
Multiple myeloma is a biologically heterogenous plasma-cell disorder. In this study, we aimed at dissecting the functional impact on transcriptome of gene mutations, copy-number abnormalities (CNA), and chromosomal rearrangements (CR). Moreover, we applied a geno-transcriptomic approach to identify specific biomarkers for personalized treatments.

Experimental Design:
We analyzed 514 newly diagnosed patients from the IA12 release of the CoMMpass study, accounting for mutations in multiple myeloma driver genes, structural variants, copy-number segments, and raw-transcript counts. We performed an in silico drug sensitivity screen (DSS), interrogating the Cancer Dependency Map (DepMap) dataset after anchoring cell lines to primary tumor samples using the Celligner algorithm.

Results:
Immunoglobulin translocations, hyperdiploidy and chr(1q)gain/amps were associated with the highest number of deregulated genes. Other CNAs and specific gene mutations had a lower but very distinct impact affecting specific pathways. Many recurrent genes showed a hotspot (HS)-specific effect. The clinical relevance of double-hit multiple myeloma found strong biological bases in our analysis. Biallelic deletions of tumor suppressors and chr(1q)-amplifications showed the greatest impact on gene expression, deregulating pathways related to cell cycle, proliferation, and expression of immunotherapy targets. Moreover, our in silico DSS showed that not only t(11;14) but also chr(1q)gain/amps and CYLD inactivation predicted differential expression of transcripts of the BCL2 axis and response to venetoclax.

Conclusions:
The multiple myeloma genomic architecture and transcriptome have a strict connection, led by CNAs and CRs. Gene mutations impacted especially with HS-mutations of oncogenes and biallelic tumor suppressor gene inactivation. Finally, a comprehensive geno-transcriptomic analysis allows the identification of specific deregulated pathways and candidate biomarkers for personalized treatments in multiple myeloma.
Multiomic Analysis Reveals Comprehensive Tumor Heterogeneity and Distinct Immune Subtypes in Multifocal Intrahepatic Cholangiocarcinoma
Authors: Chen Shuling , Xie Yubin , Cai Yuhong , Hu Huanjing , He Minghui , Liu Lijuan , Liao Changyi , Wang Yuanqi , Wang Jianping , Ren Xiaoxue , Zeng Qianwen , Peng Hong , Shen Shunli , Li Shaoqiang , Li Dongming , Lai Jiaming , Peng Baogang , Ren Jian , Kuang Ming , Peng Sui 
Published: September 2021

Abstract

Purpose:
Targeted therapy and immunotherapy are transforming the treatment approach for intrahepatic cholangiocarcinoma (ICC). However, little is known about the intertumor heterogeneity (ITH) of multifocal ICC and its impacts on patient response to these treatments. We aimed to characterize the immunogenomic and epigenomic heterogeneity of multifocal ICC to guide treatment decision making.

Experimental Design:
We obtained 66 tumor samples from 16 patients with multifocal ICC and characterized the tumor and immune heterogeneity using whole-exome sequencing, bulk and single-cell RNA sequencing, methylation microarray, and multiplex immunostaining. Patients were divided into high- or low-ITH groups according to the median ITH index. Two independent cohorts were used to validate findings. Responses to anti-PD-1 therapy were assessed.

Results:
Multifocal ICC presented considerable intertumor genomic, transcriptional, and epigenomic heterogeneity within a patient in high ITH group. The immune profile among multiple tumors within a patient was relatively less heterogeneous in high- or low-ITH group, and consistent responses of multiple tumors to anti-PD-1 immunotherapy were observed. Unsupervised clustering of immune markers identified one low and one high immune subtype, with higher immune cell infiltration, closer tumor–immune cell interactions, and upregulated IFN-signature expression in high-immune subtype. Determining expression levels of CD8B and ICOS facilitated this immune classification and prediction of patient prognosis. Finally, promoter DNA methylation contributed to different immune profiles of two subtypes by regulating immune-gene expression.

Conclusions:
There is comprehensive heterogeneity in the genome, transcriptome, and epigenome of multifocal ICC. On the basis of the less heterogeneous immune profile of ICC, we suggest an immune classification that stratifies patients' prognosis and may support personalized immunotherapy.
High efficiency Doherty power amplifiers for modern wireless communication systems: A brief review
Authors: Mabrok Mussa , Zakaria Zahriladha , Sutikno Tole 
Published: September 2021

Due<span lang="EN-MY">to the high peak to average power ratio (PAPR) of modern modulated signals, power amplifiers (PAs) have been forced to operate at the back-off (BO) region of their saturation power in order to avoid signal clipping and distortion. However, classical PAs suffer from low efficiency in the BO region operation. Therefore, efficiency has to be enhanced in that region. Many techniques have been proposed. Among them, the Doherty power amplifier (DPA) is considered as the most suitable technique due to its simple structure and high performance. However, its conventional design is limited to a 6 dB BO level, which does not satisfy the requirements of modern communication systems. In this paper, a brief review of the most significant techniques of high-efficiency DPA is presented. First, DPA topology and its operation principles are briefly discussed. Second, efficiency enhancement techniques such as an asymmetrical DPA, output combiner modification, gate bias adaption, offset line optimization, and multi-way DPA were discussed. The study shows that the most suitable, simple, and effective solution is an asymmetrical approach. However, it needs to be investigated in terms of bandwidth in order to meet the efficiency-bandwidth requirements of modern wireless communication systems such as </span>5G.
Prognostic Value of Complementary Echocardiography and Magnetic Resonance Imaging Quantitative Evaluation for Isolated Tricuspid Regurgitation
Authors: Wang Tom Kai Ming , Akyuz Kevser , Reyaldeen Reza , Griffin Brian P. , Popovic Zoran B. , Pettersson Gosta B. , Gillinov A. Marc , Flamm Scott D. , Xu Bo , Desai Milind Y. 
Published: September 2021

Background:
Isolated tricuspid regurgitation (TR) remains a management dilemma with poor outcomes. Echocardiography and cardiac magnetic resonance imaging (CMR) are valuable tools for evaluating TR, but their prognostic utility has rarely been studied together in this setting. We aimed to determine the prognostic value and thresholds for echocardiography and CMR parameters for isolated severe TR.

Methods:
Consecutive patients with isolated severe TR by echocardiography and undergoing CMR during January 2007 to June 2019 were studied. Echocardiography and CMR-derived quantitative parameters were analyzed for independent associations with and thresholds for predicting the primary end point of all-cause mortality during follow-up.

Results:
Among 262 patients studied, mean age was 62.8±15.6 years, 156 (59.5%) were females, 207 (79.0%) had secondary TR, and 87 (33.2%) underwent tricuspid valve surgery after CMR. There were 68 (26.0%) deaths during a mean follow-up of 2.5 years. Both CMR-derived tricuspid regurgitant fraction (per 5% increase) and right ventricle free wall longitudinal strain (per 1% decrease in magnitude) were independently associated with worse survival, with hazard ratios (95% CIs) of 1.15 (1.05–1.25) and 1.10 (1.04–1.17), respectively, along with right heart failure symptoms of 2.03 (1.14–3.60), while tricuspid valve surgery was borderline protective with 0.55 (0.31–0.997). Regurgitant fraction ≥30%, regurgitant volume ≥35 mL and right ventricle free wall longitudinal strain ≥−11% (by velocity vector imaging technique, which yields lower magnitude values than other conventional strain techniques) were the optimal thresholds for mortality during follow-up.

Conclusions:
TR quantification by CMR and right ventricle free wall longitudinal strain by echocardiography were the key imaging parameters independently associated with reduced survival in isolated TR, incremental to conventional clinical factors. Clinically significant thresholds for these parameters were determined and may help guide decision-making for TR management.
PDE1 Inhibition Modulates Ca
v
1.2 Channel to Stimulate Cardiomyocyte Contraction
Authors: Muller Grace K. , Song Joy , Jani Vivek , Wu Yuejin , Liu Ting , Jeffreys William P.D. , O’Rourke Brian , Anderson Mark E. , Kass David A. 
Published: September 2021

Rationale:

cAMP activation of PKA (protein kinase A) stimulates excitation-contraction (EC) coupling, increasing cardiac contractility. This is clinically achieved by β-ARs (β-adrenergic receptor) stimulation or PDE3i (inhibition of phosphodiesterase type-3), although both approaches are limited by arrhythmia and chronic myocardial toxicity. PDE1i (Phosphodiesterase type-1 inhibition) also augments cAMP and enhances contractility in intact dogs and rabbits. Unlike β-ARs or PDE3i, PDE1i-stimulated inotropy is unaltered by β-AR blockade and induces little whole-cell Ca
2+
(intracellular Ca
2+
concentration; [Ca
2+
]
i
) increase. Positive inotropy from PDE1i was recently reported in human heart failure. However, mechanisms for this effect remain unknown.

Objective:
Define the mechanism(s) whereby PDE1i increases myocyte contractility.

Methods and Results:

We studied primary guinea pig myocytes that express the PDE1C isoform found in larger mammals and humans. In quiescent cells, the potent, selective PDE1i (ITI-214) did not alter cell shortening or [Ca
2+
]
i
, whereas β-ARs or PDE3i increased both. When combined with low-dose adenylate cyclase stimulation, PDE1i enhanced shortening in a PKA-dependent manner but unlike PDE3i, induced little [Ca
2+
]
i
rise nor augmented β-ARs. β-ARs or PDE3i reduced myofilament Ca
2+
sensitivity and increased sarcoplasmic reticulum Ca
2+
content and phosphorylation of PKA-targeted serines on TnI (troponin I), MYBP-C (myosin binding protein C), and PLN (phospholamban). PDE1i did not significantly alter any of these. However, PDE1i increased Ca
v
1.2 channel conductance similarly as PDE3i (both PKA dependent), without altering Na
+
-Ca
2+
exchanger current density. Cell shortening and [Ca
2+
]
i
augmented by PDE1i were more sensitive to Ca
v
1.2 blockade and to premature or irregular cell contractions and [Ca
2+
]
i
transients compared to PDE3i.

Conclusions:

PDE1i enhances contractility by a PKA-dependent increase in Ca
v
1.2 conductance with less total [Ca
2+
]
i
increase, and no significant changes in sarcoplasmic reticulum [Ca
2+
], myofilament Ca
2+
-sensitivity, or phosphorylation of critical EC-coupling proteins as observed with β-ARs and PDE3i. PDE1i could provide a novel positive inotropic therapy for heart failure without the toxicities of β-ARs and PDE3i.
Ethics, Interpretive Social Science and War
Authors: Frost Mervyn 
Published: September 2021

Abstract
This chapter explores radical interpretivism as an approach to understanding contemporary war and the implications that flow from its application to questions about what ought to be done in contemporary asymmetrical wars. It argues that the currently dominant version of the relationship between just war theory and the world to which it is to be applied is misguided. It is widely held that policymakers facing ethical decisions about war and peace, have first to ascertain the empirical state of affairs in which they find themselves, and then, in a second step, consider what it would be ethical to do, given the circumstances. On this view, questions about the justice of going to war arise only after the completion of an empirical analysis about how things stand in the world. Radical interpretivism denies the possibility of determining a given “state of affairs” in social relations in purely empirical terms that do not involve engaging with ethical considerations from the outset. A central strand of the argument is that in the analyses of the circumstances that precede wars, what must be understood are the histories of actions and reactions of the parties involved. These, as is the case with all actions, can only be understood within the social practices in which the actors are participating. Such understandings involve an ethical engagement at every point. This interpretive approach is particularly important for a proper understanding of asymmetrical wars.