bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rigidity in Parkinson’s disease: evidence from biomechanical and neurophysiological measures
Authors: Asci Francesco , Falletti Marco , Zampogna Alessandro , Patera Martina , Hallett Mark , Rothwell John , Suppa Antonio 
Published: April 2023

Abstract
Although rigidity is a cardinal motor sign in patients with Parkinson’s disease (PD), the instrumental measurement of this clinical phenomenon is largely lacking, and its pathophysiological underpinning remains still unclear. Further advances in the field would require innovative methodological approaches able to measure parkinsonian rigidity objectively, discriminate the different biomechanical sources of muscle tone (neural or visco-elastic components), and finally clarify the contribution to ‘objective rigidity’ exerted by neurophysiological responses, which have previously been associated with this clinical sign (i.e. the long-latency stretch-induced reflex).
Twenty patients with PD (67.3 ± 6.9 years) and 25 age- and sex-matched controls (66.9 ± 7.4 years) were recruited. Rigidity was measured clinically and through a robotic device. Participants underwent robot-assisted wrist extensions at seven different angular velocities randomly applied, when ON therapy. For each value of angular velocity, several biomechanical (i.e. elastic, viscous and neural components) and neurophysiological measures (i.e. short and long-latency reflex and shortening reaction) were synchronously assessed and correlated with the clinical score of rigidity (i.e. Unified Parkinson’s Disease Rating Scale—part III, subitems for the upper limb).
The biomechanical investigation allowed us to measure ‘objective rigidity’ in PD and estimate the neuronal source of this phenomenon. In patients, ‘objective rigidity’ progressively increased along with the rise of angular velocities during robot-assisted wrist extensions. The neurophysiological examination disclosed increased long-latency reflexes, but not short-latency reflexes nor shortening reaction, in PD compared with control subjects. Long-latency reflexes progressively increased according to angular velocities only in patients with PD. Lastly, specific biomechanical and neurophysiological abnormalities correlated with the clinical score of rigidity.
‘Objective rigidity’ in PD correlates with velocity-dependent abnormal neuronal activity. The observations overall (i.e. the velocity-dependent feature of biomechanical and neurophysiological measures of objective rigidity) would point to a putative subcortical network responsible for ‘objective rigidity’ in PD, which requires further investigation.
Functional topography of the neocortex predicts covariation in complex cognitive and basic motor abilities
Authors: Whitman Ethan T , Knodt Annchen R , Elliott Maxwell L , Abraham Wickliffe C , Cheyne Kirsten , Hogan Sean , Ireland David , Keenan Ross , Leung Joan H , Melzer Tracy R , Poulton Richie , Purdy Suzanne C , Ramrakha Sandhya , Thorne Peter R , Caspi Avshalom , Moffitt Terrie E , Hariri Ahmad R 
Published: April 2023

Abstract
Although higher-order cognitive and lower-order sensorimotor abilities are generally regarded as distinct and studied separately, there is evidence that they not only covary but also that this covariation increases across the lifespan. This pattern has been leveraged in clinical settings where a simple assessment of sensory or motor ability (e.g. hearing, gait speed) can forecast age-related cognitive decline and risk for dementia. However, the brain mechanisms underlying cognitive, sensory, and motor covariation are largely unknown. Here, we examined whether such covariation in midlife reflects variability in common versus distinct neocortical networks using individualized maps of functional topography derived from BOLD fMRI data collected in 769 45-year-old members of a population-representative cohort. Analyses revealed that variability in basic motor but not hearing ability reflected individual differences in the functional topography of neocortical networks typically supporting cognitive ability. These patterns suggest that covariation in motor and cognitive abilities in midlife reflects convergence of function in higher-order neocortical networks and that gait speed may not be simply a measure of physical function but rather an integrative index of nervous system health.
Immunogenicity and Safety of Hepatitis B Virus (HBV) Vaccine With a Toll-Like Receptor 9 Agonist Adjuvant in HBV Vaccine-Naïve People With Human Immunodeficiency Virus
Authors: Marks Kristen M , Kang Minhee , Umbleja Triin , Avihingsanon Anchalee , Sugandhavesa Patcharaphan , Cox Andrea L , Vigil Karen , Perazzo Hugo , Price Jennifer C , Katsidzira Leolin , Vernon Christina , Alston-Smith Beverly , Sherman Kenneth E ,   ACTG 5379 Study Team, Alli Oladapo , Beijer Ceora , Caruso Stephanie , Cermak Mary Allegra , Chiambah Shawn , Collins Lillian , Epperson Kim , Giguel Francoise , Knowles Kevin , Kosmyna Jan , Leonard Michael , Marzinek Philip , Mohammed Terence , Zabih Sarah , Sowah Leonard , Hyer Randy 
Published: April 2023

Abstract
In this international, multicenter open-label study (ACTG A5379) of HepB-CpG vaccine in people with human immunodeficiency virus (HIV) without prior hepatitis B virus (HBV) vaccination, all 68 participants achieved HBV seroprotective titers after the 3-dose series in the primary analysis. No unexpected safety issues were observed.
Designing Effective Teacher Performance Pay Programs: Experimental Evidence from Tanzania*
Authors: Mbiti Isaac , Romero Mauricio , Schipper Youdi 
Published: April 2023

Abstract
We use a nationally representative field experiment in Tanzania to compare two teacher performance pay systems in public primary schools: a ‘pay-for-percentile’ system (a rank-order tournament) and a ‘levels’ system that features multiple proficiency thresholds. Pay for percentile can potentially induce socially optimal effort among teachers, while levels systems can encourage teachers to focus on students near passing thresholds. Despite the theoretical advantage of the tournament system, we find that both systems improved student test scores across the distribution of initial learning levels after two years. However, the levels system is easier to implement and is more cost effective.
Investigating seismic mode conversions from an ultra-high-velocity caprock by physical modelling, numerical simulations and a Gulf of Mexico salt proximity VSP survey
Authors: Zong Jingjing , Stewart Robert R , Yang Jizhong , Dyaur Nikolay , Wo Yukai 
Published: April 2023

SUMMARYSalt structures are widely distributed in many basins worldwide and play an important role in understanding tectonic movements, offering underground storage and sealing hydrocarbon traps. In addition to the acknowledged difficulties in mapping complex salt structures through seismic methods, when an evaporitic layer, such as anhydrite, forms over salt, it can introduce strong multimode conversions that can couple with the primary compressional wavefields and generate artefacts in resulting acoustic images. From two well-log suites from the Gulf of Mexico, we identify thin evaporitic caprocks on top of their salt bodies and analyse their elastic properties. Through controlled experiments, including physical and numerical modelling with a vertical seismic profiling survey geometry, we observe significant shear-mode conversions at the top of the ultra-high-velocity caprock, which further result in a family of prominent S and P (converted from S wave) modes across the top of the salt region. Similarly, in a field survey, we identify evident converted S waves and a multimode P wave (converted S wave in the anhydrite layer, and P wave elsewhere) following the primary P transmission inside the salt body. While separating the converted Smodes at the receiver end is more unambiguous, the multimode P waves could behave very similarly to the primary Pmodes and are more difficult to suppress. Under the common acoustic assumption of seismic velocity model building and imaging, complex mode conversions on top of the salt are generally ignored. Through controlled experiments and a field survey, we analyse the pitfalls associated with this omission. We emphasize the importance of understanding the physics of wave partitioning in the presence of a thin ultra-high-velocity layer on the top of the salt.
Pursuing the Innovation Economy: Implications for Startup Labour
Authors: Rose Emily 
Published: April 2023

Abstract
This article considers how the UK and Scottish governments’ policy push to promote the innovation economy affects labour. It applies a regulatory approach to consider the issue, focusing specifically on the co-ordinated efforts of government, universities and the private sector to promote and support technology startups. Data is drawn from an empirical case study of the digital technology sector in Scotland. My analysis is 2-fold. First, I demonstrate how the performance of this regulation constitutes people as startup employees. It does this by increasing the quantitative supply of labour, but also by shaping the qualitative features of that supply. The practices of government, universities and the private sector give rise to particular norms within the startup community that shape the way that startups operate as well as startup actors’ knowledge, values and general sense of how things should be done in the sector. Second, I examine how labour law interacts with these newly situated employees. I focus on the legally structured relation of subordination of employees to employers and argue that the norms the multi-actor regulatory effort promotes within the startup community have direct bearing on how this manifests in the sector.
Triple-negative breast cancer cells invade adipocyte/preadipocyte-encapsulating geometrically inverted mammary organoids
Authors: Mertz David R , Parigoris Eric , Sentosa Jason , Lee Ji-Hoon , Lee Soojung , Kleer Celina G , Luker Gary , Takayama Shuichi 
Published: April 2023

AbstractThis paper describes the manufacture of geometrically inverted mammary organoids encapsulating primary mammary preadipocytes and adipocytes. Material manipulation in an array of 192 hanging drops induces cells to self-assemble into inside-out organoids where an adipose tissue core is enveloped by a cell-produced basement membrane, indicated by laminin V staining and then a continuous layer of mammary epithelial cells. This inverted tissue structure enables investigation of multiple mammary cancer subtypes, with a significantly higher extent of invasion by triple-negative MDA-MB-231 breast cancer cells compared to MCF7 cells. By seeding cancer cells into co-culture around pre-formed organoids with encapsulated preadipocytes/adipocytes, invasion through the epithelium, then into the adipose core is observable through acquisition of confocal image stacks of whole mount specimens. Furthermore, in regions of the connective tissue core where invasion occurs, there is an accumulation of collagen in the microenvironment. Suggesting that this collagen may be conducive to increased invasiveness, the anti-fibrotic drug pirfenidone shows efficacy in this model by slowing invasion. Comparison of adipose tissue derived from three different donors shows method consistency as well as the potential to evaluate donor cell-based biological variability.Insight box Geometrically inverted mammary organoids encapsulating primary preadipocytes/adipocytes (P/As) are bioengineered using a minimal amount of Matrigel scaffolding. Use of this eversion-free method is key to production of adipose mammary organoids (AMOs) where not only the epithelial polarity but also the entire self-organizing arrangement, including adipose position, is inside-out. While an epithelial-only structure can analyze cancer cell invasion, P/As are required for invasion-associated collagen deposition and efficacy of pirfenidone to counteract collagen deposition and associated invasion. The methods described strike a balance between repeatability and preservation of biological variability: AMOs form consistently across multiple adipose cell donors while revealing cancer cell invasion differences.
Limited, asymmetric hybridization between coastal cutthroat trout and steelhead in a Northern California river
Authors: Rizza Samuel F , Wilzbach Margaret A , Kinziger Andrew P , Anderson Eric C , Carlos Garza John 
Published: April 2023

Abstract
Hybridization between coastal cutthroat trout (Oncorhynchus clarkii clarkii) and steelhead (O. mykiss) was assessed in the Smith River, California. Individuals were categorized as pure or as 1 of 10 hybrid classes using 30 “diagnostic” single-nucleotide polymorphisms positioned on 26 separate chromosomes. Most of the individuals examined (n = 876), were pure coastal cutthroat trout (n = 634) or pure steelhead (n = 213), and 29 individuals were identified as having hybrid ancestry. Among hybrids, first generation hybrids (n = 15) and coastal cutthroat trout backcrosses (n = 12) were the most common. No individuals were identified as backcrosses to SH, suggesting the presence of genetic or behavioral mechanisms constraining such backcrosses, or the growth and survival of their progeny. Mitochondrial DNA of 14 of 15 F1 hybrids was of steelhead origin, suggesting that hybridization was driven primarily by sneak-mating of male coastal cutthroat trout with female steelhead. Evaluation of classical phenotypic characters for coastal cutthroat trout and steelhead (i.e. jaw slash, maxillary length, and hyoid teeth) were not reliable by themselves for identification of either pure parental fish or hybrids. In contrast, analysis with geometric morphometrics revealed distinctive body shapes for pure coastal cutthroat trout and steelhead, and the combination of classical traits and geometric morphology was mostly accurate in distinguishing them. However, first generation hybrids and backcrosses overlapped completely with parental types, highlighting challenges in hybrid identification using phenotypic traits.
Rac2 regulates immune complex–mediated granule polarization and exocytosis in neutrophils
Authors: Ilarraza Ramses , Chao Danny V , Bodman James A R , Chesley Alexandra , Humble Adam , Shaheen Farzana , Eitzen Gary , Lacy Paige 
Published: April 2023

Abstract
A key molecule for neutrophil degranulation is Rac2 guanosine triphosphatase. Neutrophils from Rac2 knockout mice (Rac2−/−) exhibit impaired primary granule exocytosis in response to cytochalasin B/f-Met-Leu-Phe, while secondary and tertiary granule release is unaffected. Coronin 1A, a protein involved in actin remodeling, is diminished in Rac2−/− neutrophils. However, primary granule exocytosis from Rac2−/− neutrophils has not been determined using more immunologically relevant stimuli. We sought to determine the role of Rac2 in degranulation and actin cytoskeleton rearrangement in response to immobilized immune complexes and relate this to intracellular coronin 1A localization. We used bone marrow neutrophils from wild-type and Rac2−/− mice stimulated with immobilized immune complexes. Secretion of primary (myeloperoxidase), secondary (lactoferrin), and tertiary granule (MMP-2 and MMP-9) products was evaluated. Subcellular colocalization of coronin 1A with actin and the primary granule marker CD63 was determined by deconvolution microscopy. We found major differences in myeloperoxidase, MMP-2, and MMP-9 but not lactoferrin release, along with diminished filopodia formation, CD63 polarization, and colocalization of coronin 1A with CD63 in immune complex–stimulated Rac2−/− bone marrow neutrophils. Rac2 and coronin 1A were found associated with granules in cytochalasin B/f-Met-Leu-Phe–activated human neutrophils. This report confirms a role for Rac2 in immunologically relevant stimulation of neutrophil granule exocytosis. Rac2 appears to attach to neutrophil granules, polarize CD63+ granules to the cell surface in a manner dependent on coronin 1A, and induce filopodia formation. Our studies provide insight into mechanisms of Rac2-mediated regulation of granule exocytosis.
Microsatellite instability in noncolorectal and nonendometrial malignancies in patients with Lynch syndrome
Authors: Elze Lisa , van der Post Rachel S , Vos Janet R , Mensenkamp Arjen R , de Hullu Mirjam S C , Nagtegaal Iris D , Hoogerbrugge Nicoline , de Voer Richarda M , Ligtenberg Marjolijn J L 
Published: April 2023

Abstract

Background
Individuals with Lynch syndrome are at increased hereditary risk of colorectal and endometrial carcinomas with microsatellite instability (MSI-H) and mismatch repair-deficiency (dMMR), which make these tumors vulnerable to therapy with immune checkpoint inhibitors. Our aim is to assess how often other tumor types in these individuals share these characteristics.

Methods
We retrieved the full tumor history of a historical clinic-based cohort of 1745 individuals with Lynch syndrome and calculated the standardized incidence ratio for all tumor types. MSI status, somatic second hit alterations, and immunohistochemistry-based MMR status were analyzed in 236 noncolorectal and nonendometrial malignant tumors.

Results
In individuals with Lynch syndrome MSI-H/dMMR occurred both in Lynch-spectrum and in non–Lynch-spectrum malignancies (85% vs 37%, P &lt; .01). MSI-H/dMMR malignancies were found in nearly all non–Lynch-spectrum tumor types. A high percentage (33%) of breast carcinomas with medullary features was observed, and most of them were MSI-H/dMMR. Breast carcinoma with medullary features were shown to be associated with Lynch syndrome (standardized incidence ratio = 38.8, 95% confidence interval = 16.7 to 76.5).

Conclusions
In individuals with Lynch syndrome, MSI-H/dMMR occurs in more than one-half of the malignancies other than colorectal and endometrial carcinomas, including tumor types without increased incidence. The Lynch-spectrum tumors should be expanded to breast carcinomas with medullary features. All malignancies in patients with Lynch syndrome, independent of subtype, should be tested for MSI-H/dMMR in case therapy with immune checkpoint inhibitors is considered. Moreover, Lynch syndrome should be considered an underlying cause of all MSI-H/dMMR malignancies other than colorectal and endometrial carcinomas.
A spline-based time-varying reproduction number for modelling epidemiological outbreaks
Authors: Pircalabelu Eugen 
Published: April 2023

AbstractWe develop in this manuscript a method for performing estimation and inference for the reproduction number of an epidemiological outbreak, focusing on the COVID-19 epidemic. The estimator is time-dependent and uses spline modelling to adapt to changes in the outbreak. This is accomplished by directly modelling the series of new infections as a function of time and subsequently using the derivative of the function to define a time-varying reproduction number, which is then used to assess the evolution of the epidemic for several countries.
Tracing the kinematics of the whole ram-pressure-stripped tails in ESO 137-001
Authors: Luo Rongxin , Sun Ming , Jáchym Pavel , Waldron Will , Fossati Matteo , Fumagalli Michele , Boselli Alessandro , Combes Francoise , Kenney Jeffrey D P , Li Yuan , Gronke Max 
Published: April 2023

ABSTRACT
Ram pressure stripping (RPS) is an important process to affect the evolution of cluster galaxies and their surrounding environment. We present a large MUSE mosaic for ESO 137-001 and its stripped tails, and study the detailed distributions and kinematics of the ionized gas and stars. The warm, ionized gas is detected to at least 87 kpc from the galaxy and splits into three tails. There is a clear velocity gradient roughly perpendicular to the stripping direction, which decreases along the tails and disappears beyond ∼45 kpc downstream. The velocity dispersion of the ionized gas increases to ∼80 km s−1 at ∼20 kpc downstream and stays flat beyond. The stars in the galaxy disc present a regular rotation motion, while the ionized gas is already disturbed by the ram pressure. Based on the observed velocity gradient, we construct the velocity model for the residual galactic rotation in the tails and discuss the origin and implication of its fading with distance. By comparing with theoretical studies, we interpreted the increased velocity dispersion as the result of the oscillations induced by the gas flows in the galaxy wake, which may imply an enhanced degree of turbulence there. We also compare the kinematic properties of the ionized gas and molecular gas from ALMA, which shows they are co-moving and kinematically mixed through the tails. Our study demonstrates the great potential of spatially resolved spectroscopy in probing the detailed kinematic properties of the stripped gas, which can provide important information for future simulations of RPS.
Impact of thermal misbalance on acoustic-gravity waves in the solar atmosphere
Authors: Riashchikov D S , Molevich N E , Zavershinskii D I 
Published: April 2023

ABSTRACT
The joint effect of gravity and thermal misbalance on the dynamics of acoustic-gravity waves (AGW) in the solar atmosphere is considered. It is shown that the heating and cooling taken in the form of power functions lead to the linear dependence of stationary temperature profile. Estimates of the ratio of the characteristic length associated with thermal processes to the gravitational height show a predominant influence of thermal processes in the temperature range up to 2 MK and a comparable influence on the dynamics of AGW in the range from 2 to 10 MK. A study of the dispersion properties of AGW in an isothermal atmosphere showed that in regimes with an overwhelming influence of thermal processes, the acoustic cut-off frequency decreases up to $\sqrt{\gamma }$ times. At the same time, the maximum frequency of the gravitational mode (analogue of the Brunt–Väisälä frequency in the medium without non-adiabatic heating and cooling) decreases with increasing power of thermal processes, and then the gravitational mode can become purely oscillatory.
Extended line emission in the BCG of Abell 2390
Authors: Alcorn Leo Y , Yee H K C , Drissen Laurent , Rhea Carter , Sivanandam Suresh , Hlavacek-Larrondo Julie , Hsieh Bau-Ching , Lin Lihwai , Lin Yen-Ting , Liu Qing , Muzzin Adam , Noble Allison , Pintos-Castro Irene 
Published: April 2023

ABSTRACT
We report CFHT/SITELLE imaging Fourier Transform Spectrograph observations of the brightest cluster galaxy (BCG) of galaxy cluster Abell 2390 at z = 0.228. The BCG displays a prominent cone of emission in H α, H β, [N ii], and [O ii] to the North-West with PA = 42°, 4.4 arcsec in length (15.9 kpc), which is associated with elongated and asymmetric Chandra soft X-ray emission. The H α flux map also contains a ‘hook’ of H α and [N ii] emission resulting in a broadened northern edge to the cone. Using SITELLE/LUCI software, we extract emission line flux, velocity, velocity dispersion, and continuum maps, and utilize them to derive flux ratio maps to determine ionization mechanisms and dynamical information in the BCG’s emission line region. The Baldwin–Phillips–Terlevich diagnostics on the BCG cone indicate a composite ionization origin of photoionization due to star formation and shock. Strong LINER-like emission is seen in the nuclear region which hosts an active galactic nucleus (AGN). As Abell 2390 is a cool-core cluster, we suggest that the cooling flow is falling onto the central BCG and interacting with the central AGN. The AGN produces jets that inflate ‘bubbles’ of plasma in the ICM, as is often observed in local galaxy clusters. Furthermore, combining signs of AGN activities from radio, optical emission line and X-ray data over a large range of physical scale, we find evidence for three possible episodes of AGN activity in different epochs associated with the Abell 2390 BCG.