bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflation is always semi-classical: diffusion domination overproduces Primordial Black Holes
Authors: Rigopoulos G. , Wilkins A. 
Published: December 2021

Abstract
We use the Hamilton-Jacobi (H-J) formulation of stochastic inflation to describe the evolution of the inflaton during a period of Ultra-Slow Roll (USR), taking into account the field's velocity and its gravitational backreaction. We demonstrate how this formalism allows one to modify existing slow-roll (SR) formulae to be fully valid outside of the SR regime. We then compute the mass fraction, β, of Primordial Black Holes (PBHs) formed by a plateau in the inflationary potential. By fully accounting for the inflaton velocity as it enters the plateau, we find that PBHs are generically overproduced before the inflaton's velocity reaches zero, ruling out a period of free diffusion or even stochastic noise domination on the inflaton dynamics. We also examine a local inflection point and similarly conclude that PBHs are overproduced before entering a quantum diffusion dominated regime. We therefore surmise that the evolution of the inflaton is always predominantly classical with diffusion effects always subdominant. Both the plateau and the inflection point are characterized by a very sharp transition between the under- and over-production regimes. This can be seen either as severe fine-tunning on the inflationary production of PBHs, or as a very strong link between the fraction β and the shape of the potential and the plateau's extent.
Cosmological constraints from unWISE and Planck CMB lensing tomography
Authors: Krolewski Alex , Ferraro Simone , White Martin 
Published: December 2021

Abstract
A number of recent, low-redshift, lensing measurements hint
at a universe in which the amplitude of lensing is lower than that
predicted from the ΛCDM model fit to the data of the Planck
CMB mission. Here we use the auto- and cross-correlation signal of
unWISE galaxies and Planck CMB lensing maps to infer cosmological
parameters at low redshift. In particular, we consider three unWISE
samples (denoted as "blue", "green" and "red") at median
redshifts z ∼ 0.6, 1.1 and 1.5, which fully cover the Dark
Energy dominated era. Our cross-correlation measurements, with
combined significance S/N ∼ 80, are used to infer the amplitude
of low-redshift fluctuations, σ8; the fraction of matter in
the Universe, Ω
m
; and the combination S8 ≡ σ8
(Ω
m
/0.3)0.5 to which these low-redshift lensing
measurements are most sensitive. The combination of blue, green and
red samples gives a value S
m
= 0.784 ± 0.015, that is fully
consistent with other low-redshift lensing measurements and in
2.4σ tension with the CMB predictions from Planck. This is
noteworthy, because CMB lensing probes the same physics as previous
galaxy lensing measurements, but with very different systematics,
thus providing an excellent complement to previous measurements.
Covariant decomposition of the non-linear galaxy number counts and their monopole
Authors: Ginat Yonadav Barry , Desjacques Vincent , Jeong Donghui , Schmidt Fabian 
Published: December 2021

Abstract
We present a fully non-linear and relativistically covariant expression for the observed galaxy density contrast. Building on a null tetrad tailored to the cosmological observer's past light cone, we find a decomposition of the non-linear galaxy over-density into manifestly gauge-invariant quantities, each of which has a clear physical interpretation as a cosmological observable. This ensures that the monopole of the galaxy over-density field (the mean galaxy density as a function of observed redshift) is properly accounted for. We anticipate that this decomposition will be useful for future work on non-linearities in galaxy number counts, for example, deriving the relativistic expression for the galaxy bispectrum. We then specialise our results to conformal Newtonian gauge, with a Hubble parameter either defined globally or measured locally, illustrating the significance of the different contributions to the observed monopole of the galaxy density.
A comparison of traceable spatial angle autocollimator calibrations performed by PTB and VTT MIKES
Authors: Geckeler Ralf D , Schumann Matthias , Just Andreas , Krause Michael , Lassila Antti , Heikkinen Ville 
Published: December 2021

Abstract
Autocollimators are versatile devices for angle metrology used in a wide range of applications in engineering and manufacturing. A modern electronic autocollimator generally features two measuring axes and can thus fully determine the surface normal of an optical surface relative to it in space. Until recently, however, the calibration capabilities of the National Metrology Institutes were limited to plane angles. Although it was possible to calibrate both measuring axes independently of each other, it was not feasible to determine their crosstalk if angular deflections were present in both axes simultaneously. To expand autocollimator calibrations from plane angles to spatial angles, PTB and VTT MIKES have created dedicated calibration devices which are based on different measurement principles and accomplish the task of metrological traceability in different ways. Comparing calibrations of a transfer standard makes it possible to detect systematic measurement errors of the two devices and to evaluate the validity of their uncertainty budgets. The uncertainty levels of the devices are comparable to each other, with an expanded uncertainty U = 0.014 arcsecond (95.5% coverage probability) over a measuring range of ±1000 arcsecond in the case of PTB and U = 0.015 arcsecond over a range of ±500 arcsecond and U = 0.020 arcsecond over ±1000 arcsecond in the case of VTT MIKES. Over a range of ±1000 arcsecond with regards to both measuring axis of an Elcomat 3000 autocollimator as a transfer standard, no statistically significant differences between the calibrations were detected. The results thus confirm the calibration capabilities of PTB and VTT MIKES as stated in the calibration and measuring capability database of Bureau International des Poids et Mesures.
Metaphysical semantics versus ground on questions of realism
Authors: Sud Rohan 
Published: December 2021

Abstract
One desideratum for a theory of fundamentality is to give us the conceptual tools to articulate fruitful metaphysical distinctions between the assortment of ‘realist’ and ‘anti-realist’ positions in a given domain such as meta-ethics. The ability to articulate such distinctions gives us a way to assess rival theories of fundamentality, such as Fine’s grounding theory and Sider’s metaphysical semantic theory. Indeed, Sider has argued that metaphysical semantic theories have an edge with respect to this desideratum and takes this as an important reason to prefer those theories over rival grounding theories. This paper takes a closer look at how the rival theories compare with respect to questions of realism and defends the grounding theorist’s ability to meet the desideratum.
Analysing an allelic series of rare missense variants of CACNA1I in a Swedish schizophrenia cohort
Authors: Baez-Nieto David , Allen Andrew , Akers-Campbell Seth , Yang Lingling , Budnik Nikita , Pupo Amaury , Shin Young-Cheul , Genovese Giulio , Liao Maofu , Pérez-Palma Eduardo , Heyne Henrike , Lal Dennis , Lipscombe Diane , Pan Jen Q. 
Published: December 2021

Abstract
CACNA1I is implicated in the susceptibility to schizophrenia by large-scale genetic association studies of single nucleotide polymorphisms. However, the channelopathy of CACNA1I in schizophrenia is unknown. CACNA1I encodes CaV3.3, a neuronal voltage-gated calcium channel that underlies a subtype of T-type current that is important for neuronal excitability in the thalamic reticular nucleus and other regions of the brain. Here, we present an extensive functional characterization of 57 naturally occurring rare and common missense variants of CACNA1I derived from a Swedish schizophrenia cohort of more than 10 000 individuals. Our analysis of this allelic series of coding CACNA1I variants revealed that reduced CaV3.3 channel current density was the dominant phenotype associated with rare CACNA1I coding alleles derived from control subjects, whereas rare CACNA1I alleles from schizophrenia patients encoded CaV3.3 channels with altered responses to voltages. CACNA1I variants associated with altered current density primarily impact the ionic channel pore and those associated with altered responses to voltage impact the voltage-sensing domain. CaV3.3 variants associated with altered voltage dependence of the CaV3.3 channel and those associated with peak current density deficits were significantly segregated across affected and unaffected groups (Fisher’s exact test, P = 0.034). Our results, together with recent data from the SCHEMA (Schizophrenia Exome Sequencing Meta-Analysis) cohort, suggest that reduced CaV3.3 function may protect against schizophrenia risk in rare cases. We subsequently modelled the effect of the biophysical properties of CaV3.3 channel variants on thalamic reticular nucleus excitability and found that compared with common variants, ultrarare CaV3.3-coding variants derived from control subjects significantly decreased thalamic reticular nucleus excitability (P = 0.011). When all rare variants were analysed, there was a non-significant trend between variants that reduced thalamic reticular nucleus excitability and variants that either had no effect or increased thalamic reticular nucleus excitability across disease status. Taken together, the results of our functional analysis of an allelic series of &gt;50 CACNA1I variants in a schizophrenia cohort reveal that loss of function of CaV3.3 is a molecular phenotype associated with reduced disease risk burden, and our approach may serve as a template strategy for channelopathies in polygenic disorders.
A recurrent machine learning model predicts intracranial hypertension in neurointensive care patients
Authors: Schweingruber Nils , Mader Marius Marc Daniel , Wiehe Anton , Röder Frank , Göttsche Jennifer , Kluge Stefan , Westphal Manfred , Czorlich Patrick , Gerloff Christian 
Published: December 2021

Abstract
The evolution of intracranial pressure (ICP) of critically ill patients admitted to a neurointensive care unit (ICU) is difficult to predict. Besides the underlying disease and compromised intracranial space, ICP is affected by a multitude of factors, many of which are monitored on the ICU, but the complexity of the resulting patterns limits their clinical use. This paves the way for new machine learning techniques to assist clinical management of patients undergoing invasive ICP monitoring independent of the underlying disease.
An institutional cohort (ICP-ICU) of patients with invasive ICP monitoring (n = 1346) was used to train recurrent machine learning models to predict the occurrence of ICP increases of ≥22 mmHg over a long (&gt;2 h) time period in the upcoming hours. External validation was performed on patients undergoing invasive ICP measurement in two publicly available datasets [Medical Information Mart for Intensive Care (MIMIC, n = 998) and eICU Collaborative Research Database (n = 1634)].
Different distances (1–24 h) between prediction time point and upcoming critical phase were evaluated, demonstrating a decrease in performance but still robust AUC-ROC with larger distances (24 h AUC-ROC: ICP-ICU 0.826 ± 0.0071, MIMIC 0.836 ± 0.0063, eICU 0.779 ± 0.0046, 1 h AUC-ROC: ICP-ICU 0.982 ± 0.0008, MIMIC 0.965 ± 0.0010, eICU 0.941 ± 0.0025). The model operates on sparse hourly data and is stable in handling variable input lengths and missingness through its nature of recurrence and internal memory. Calculation of gradient-based feature importance revealed individual underlying decisions for our long short time memory-based model and thereby provided improved clinical interpretability.
Recurrent machine learning models have the potential to be an effective tool for the prediction of ICP increases with high translational potential.
Heterozygous PRKN mutations are common but do not increase the risk of Parkinson’s disease
Authors: Zhu William , Huang Xiaoping , Yoon Esther , Bandres-Ciga Sara , Blauwendraat Cornelis , Billingsley Kimberly J , Cade Joshua H , Wu Beverly P , Williams Victoria H , Schindler Alice B , Brooks Janet , Gibbs J Raphael , Hernandez Dena G , Ehrlich Debra , Singleton Andrew B , Narendra Derek P 
Published: December 2021

Abstract
PRKN mutations are the most common recessive cause of Parkinson’s disease and are a promising target for gene and cell replacement therapies. Identification of biallelic PRKN patients at the population scale, however, remains a challenge, as roughly half are copy number variants and many single nucleotide polymorphisms are of unclear significance. Additionally, the true prevalence and disease risk associated with heterozygous PRKN mutations is unclear, as a comprehensive assessment of PRKN mutations has not been performed at a population scale.
To address these challenges, we evaluated PRKN mutations in two cohorts with near complete genotyping of both single nucleotide polymorphisms and copy number variants: the NIH-PD + AMP-PD cohort, the largest Parkinson’s disease case-control cohort with whole genome sequencing data from 4094 participants, and the UK Biobank, the largest cohort study with whole exome sequencing and genotyping array data from 200 606 participants. Using the NIH-PD participants, who were genotyped using whole genome sequencing, genotyping array, and multi-plex ligation-dependent probe amplification, we validated genotyping array for the detection of copy number variants. Additionally, in the NIH-PD cohort, functional assays of patient fibroblasts resolved variants of unclear significance in biallelic carriers and suggested that cryptic loss of function variants in monoallelic carriers are not a substantial confounder for association studies.
In the UK Biobank, we identified 2692 PRKN copy number variants from genotyping array data from nearly half a million participants (the largest collection to date). Deletions or duplications involving exon 2 accounted for roughly half of all copy number variants and the vast majority (88%) involved exons 2, 3, or 4. In the UK Biobank, we found a pathogenic PRKN mutation in 1.8% of participants and two mutations in ∼1/7800 participants. Those with one PRKN pathogenic variant were as likely as non-carriers to have Parkinson’s disease [odds ratio = 0.91 (0.58–1.38), P-value 0.76] or a parent with Parkinson’s disease [odds ratio = 1.12 (0.94–1.31), P-value = 0.19]. Similarly, those in the NIH-PD + AMP + PD cohort with one PRKN pathogenic variant were as likely as non-carriers to have Parkinson’s disease [odds ratio = 1.29 (0.74–2.38), P-value = 0.43].
Together our results demonstrate that heterozygous pathogenic PRKN mutations are common in the population but do not increase the risk of Parkinson’s disease.
High SARS-CoV-2 Viral Load and Low CCL5 Expression Levels in the Upper Respiratory Tract Are Associated With COVID-19 Severity
Authors: Pérez-García Felipe , Martin-Vicente María , Rojas-García Rosa Lía , Castilla-García Lucía , Muñoz-Gomez María José , Hervás Fernández Irene , González Ventosa Victoria , Vidal-Alcántara Erick Joan , Cuadros-González Juan , Bermejo-Martin Jesús F , Resino Salvador , Martínez Isidoro 
Published: December 2021

Abstract
Mucosal immune response in the upper respiratory tract is crucial for initial control of viral replication, clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and progression of coronavirus disease 2019 (COVID-19). We analyzed SARS-CoV-2 RNA load and expression of selected immune genes in the upper respiratory tract (nasopharynx) of 255 SARS-CoV-2–infected patients and evaluated their association with severe COVID-19. SARS-CoV-2 replication in nasopharyngeal mucosa induces expression of several innate immune genes. High SARS-CoV-2 viral load and low CCL5 expression levels were associated with intensive care unit admission or death, although CCL5 was the best predictor of COVID-19 severity.
Efficacy of Two-Stage Meek Micrografting in Patients With Severe Burns
Authors: Hu Gaozhong , Zhang Peng , Chen Yan , Yuan Zhiqiang , Song Huapei 
Published: December 2021

Abstract
Burns are common injuries associated with high disability and mortality. In recent years, Meek micrografting technique has been gradually applied for the wound treatment of severe burns. However, the efficacy of two-stage Meek micrografting in patients with severe burns keeps unclear. The data of eligible patients with severe burns who were admitted to Southwest Hospital of the Third Military Medical University from January 2013 to December 2019 were retrospectively analyzed. The patients were divided into two groups according to the Meek micrografting method: one-stage skin grafting (group A) and two-stage skin grafting (group B). The baseline data, survival rate of skin graft, length of hospital stay, treatment costs, laboratory data, and cumulative survival were statistically analyzed. One hundred and twenty-seven patients (91 in group A and 36 in group B) were included in the study. There was no significant difference in the baseline data, the length of hospital stay, and treatment costs between the two groups. The survival rate of skin graft was higher in group B. Total protein and albumin level, platelet count in group B were superior to those in group A, while there was no difference in other laboratory data (prealbumin, serum creatinine, urea nitrogen, cystatin C, blood cultures, wound exudate cultures), and cumulative survival between the two groups. Our results demonstrated that staged Meek micrografting could improve the survival rate of skin graft, by reducing the risks of hypoproteinemia, hypoalbuminemia, and low platelet counts after adequate resuscitation.
Climate Change, Inequality, and Human Migration
Authors: Burzyński Michał , Deuster Christoph , Docquier Frédéric , de Melo Jaime 
Published: December 2021

Abstract
This paper investigates the long-term implications of climate change on global migration and inequality. Accounting for the effects of changing temperatures, sea levels, and the frequency and intensity of natural disasters, we model the impact of climate change on productivity and utility in a dynamic general equilibrium framework. By endogenizing people’s migration decisions across millions of $5 \times 5$ km spatial cells, our approach sheds light on the magnitude and dyadic, education-specific structure of human migration induced by global warming. We find that climate change strongly intensifies global inequality and poverty, reinforces urbanization, and boosts migration from low- to high-latitude areas. Median projections suggest that climate change will induce a voluntary and a forced permanent relocation of 62 million working-age individuals over the course of the 21st century. Overall, under current international migration laws and policies, only a small fraction of people suffering from the negative effects of climate change manages to move beyond their homelands. We conclude that it is unlikely that climate shocks will induce massive international flows of migrants, except under combined extremely pessimistic climate scenarios and highly permissive migration policies. In contrast, poverty resulting from climate change is a real threat to all of us.
Genetic screen for suppression of transcriptional interference reveals fission yeast 14–3–3 protein Rad24 as an antagonist of precocious Pol2 transcription termination
Authors: Garg Angad , Shuman Stewart , Schwer Beate 
Published: December 2021

Abstract
Expression of fission yeast Pho1 acid phosphatase is repressed under phosphate-replete conditions by transcription of an upstream prt lncRNA that interferes with the pho1 mRNA promoter. lncRNA control of pho1 mRNA synthesis is influenced by inositol pyrophosphate (IPP) kinase Asp1, deletion of which results in pho1 hyper-repression. A forward genetic screen for ADS (Asp1 Deletion Suppressor) mutations identified the 14–3–3 protein Rad24 as a governor of phosphate homeostasis. Production of full-length interfering prt lncRNA was squelched in rad24Δ cells, concomitant with increased production of pho1 mRNA and increased Pho1 activity, while shorter precociously terminated non-interfering prt transcripts persisted. Epistasis analysis showed that pho1 de-repression by rad24Δ depends on: (i) 3′-processing and transcription termination factors CPF, Pin1, and Rhn1; and (ii) Threonine-4 of the Pol2 CTD. Combining rad24Δ with the IPP pyrophosphatase-dead asp1-H397A allele caused a severe synthetic growth defect that was ameliorated by loss-of-function mutations in CPF, Pin1, and Rhn1, and by CTD phospho-site mutations T4A and Y1F. Rad24 function in repressing pho1 was effaced by mutation of its phosphate-binding pocket. Our findings instate a new role for a 14–3–3 protein as an antagonist of precocious RNA 3′-processing/termination.
Screening and management of subclinical interstitial lung disease in systemic sclerosis: an international survey
Authors: Hoa Sabrina , Baron Murray , Hudson Marie 
Published: December 2021

Abstract

Objective
Interstitial lung disease (ILD) is the leading cause of mortality in SSc. Experts now recommend high-resolution CT (HRCT) screening in all SSc patients and treatment of subclinical ILD in SSc patients with high-risk phenotypes. We undertook an international survey to understand current screening and treatment practices in subclinical SSc-ILD.

Methods
An electronic REDCap survey was distributed to 611 general rheumatologists, 348 national and international SSc experts, 285 general respirologists and 57 ILD experts.

Results
One hundred and ninety-eight participants responded to the survey, including 135 (68%) rheumatologists and 54 (27%) respirologists. Over half (59%) of respondents routinely ordered HRCTs in all newly diagnosed SSc patients, although this practice was more common in Europe (83%), the USA (68%), Asia (73%) and Latin America (100%) compared with Canada (40%) and Australia (40%). Nearly half (48%) of respondents would not treat subclinical SSc-ILD, whereas 52% would treat or consider treatment. At least 70% would likely treat subclinical ILD in the setting of diffuse SSc, anti-topoisomerase-I autoantibodies, disease duration below 18 months, ground-glass opacities, oxygen desaturation, or significant ILD progression on imaging or pulmonary function tests. The majority (67%) of respirologists would not treat subclinical ILD. MMF was the preferred first-line drug for the treatment of subclinical SSc-ILD.

Conclusion
This international survey highlights important regional variations in SSc-ILD screening and significant heterogeneity among rheumatologists and respirologists in the treatment of subclinical SSc-ILD. High-quality research addressing these questions is needed to produce evidence-based guidelines and harmonize the approach to identification and treatment of subclinical SSc-ILD.