bluuebunny/crossref_metadata_2025_split huggingface dataset:
C-reactive protein impairs immune response of CD8+T cells via FcγRIIb-p38MAPK-ROS axis in multiple myeloma
Authors: Jiang Jinxing , Peng Ziyi , Wang Junying , Chen Mengping , Wan Yike , Huang Honghui , Liu Zhiqiang , Wang Jingya , Hou Jian 
Published: October 2023

BackgroundC-reactive protein (CRP) is a prototypical acute phase protein in humans with the function of regulating immune cells. Serum CRP levels are elevated in multiple myeloma (MM), associated with MM cell proliferation and bone destruction. However, its direct effects on T lymphocytes in MM have not been elucidated.MethodsPublic data sets were used to explore the correlation of CRP levels with immune cell infiltration and cytotoxicity score of CD8+T cells in MM. In vitro, repeated freeze-thaw myeloma cell lines were taken as tumor antigens to load dendritic cells (DCs) derived from HLA-A*0201-positive healthy donors. MM-specific cytotoxic T cells (MM-CTL) were obtained from T lymphocytes of the corresponding donors pulsed with these DCs. B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cells were manipulated by transfecting with lentivirus encoding an anti-BCMA single-chain variable fragment. Then T cells from healthy controls, MM-CTLs and BCMA CAR-T cells were exposed to CRP and analyzed for cell proliferation, cytotoxicity, immunophenotypes. CRP binding capacity to T cells before and after Fc gamma receptors IIb (FcγRIIb) blockage, p38 mitogen-activated protein kinase (MAPK) pathway and the downstream molecules were also detected. In vivo, both normal C57BL/6J mice and the Vk*MYC myeloma mouse models were applied to confirm the impact of CRP on T cells.ResultsCRP levels were negatively correlated with cell-infiltration and cytotoxicity score of CD8+T cells in MM. In vitro experiments showed that CRP inhibited T-cell proliferation in a dose-dependent manner, impaired the cytotoxic activity and upregulated expression of senescent markers in CD8+T cells. In vivo results validated the suppressive role of CRP in CD8+T cells. CRP could bind to CD8+T cells, mainly to the naïve T subset, while the binding was dramatically decreased by FcγRIIb blockage. Furthermore, CRP resulted in increased phosphorylation of p38 MAPK, elevated levels of reactive oxygen species and oxidized glutathione in CD8+T cells.ConclusionsWe found that CRP impaired immune response of CD8+T cells via FcγRIIb-p38MAPK-ROS signaling pathway. The study casted new insights into the role of CRP in anti-myeloma immunity, providing implications for future immunotherapy in MM.
B cell polygenic risk scores associate with anti-dsDNA antibodies and nephritis in systemic lupus erythematosus
Authors: Hedenstedt Anna , Reid Sarah , Sayadi Ahmed , Eloranta Maija-Leena , Skoglund Elisabeth , Bolin Karin , Frodlund Martina , Lerang Karoline , Jönsen Andreas , Rantapää-Dahlqvist Solbritt , Bengtsson Anders A , Rudin Anna , Molberg Øyvind , Sjöwall Christopher , Sandling Johanna K , Leonard Dag 
Published: October 2023

ObjectiveB cell function and autoantibodies are important in SLE pathogenesis. In this work, we aimed to investigate the impact of cumulative SLE B cell genetics on SLE subphenotype and autoantibody profile.MethodsFemale patients with SLE (n=1248) and healthy controls (n=400) were genotyped using Illumina’s Global Screening Array. Two polygenic risk scores (PRSs), one representing B cell genes and the other B cell activation genes, were calculated for each individual using risk loci for SLE in genes assigned to B cell-related pathways according to the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Reactome Databases.ResultsDouble-stranded DNA (dsDNA) antibodies were more prevalent among patients with a high compared with a low SLE B cell PRS (OR 1.47 (1.07 to 2.01), p=0.018), and effect sizes were augmented in patients with human leucocyte antigen (HLA) risk haplotypes HLA-DRB1*03:01 and HLA-DRB1*15:01 (DRB1*03/15 −/− (OR 0.99 (0.56 to 1.77), p=0.98; DRB1*03/15 +/− or −/+ (OR 1.64 (1.06 to 2.54), p=0.028; and DRB1*03/15 +/+ (OR 4.47 (1.21 to 16.47), p=0.024). Further, a high compared with a low B cell PRS was associated with low complement levels in DRB1*03/15 +/+ patients (OR 3.92 (1.22 to 12.64), p=0.022). The prevalence of lupus nephritis (LN) was higher in patients with a B cell activation PRS above the third quartile compared with patients below (OR 1.32 (1.00 to 1.74), p=0.048).ConclusionsHigh genetic burden related to B cell function is associated with dsDNA antibody development and LN. Assessing B cell PRSs may be important in order to determine immunological pathways influencing SLE and to predict clinical phenotype.
Evidence of summer thermal stratification in extreme northern lakes
Authors: Antoniades Dermot , Klanten Yohanna , Cameron Emma , Garcia-Oteyza Julia , Oliva Marc , Vincent Warwick F. 
Published: October 2023

Rapid warming in the High Arctic has induced changes in terrestrial environments that have included major recent shifts in lakes and ponds. Numerous studies exist of spatial trends in water chemistry, bioindicator groups, and paleoenvironmental change from High Arctic lakes; however, little is known about lake thermal stratification regimes at high latitudes beyond assumptions based on generalized classification schemes. Here, we report on the presence in late July 2022 of positive thermal stratification during open-water conditions in two freshwater lakes near Clements Markham Inlet, on northern Ellesmere Island. These lakes are situated in the polar desert at 82.6°N, >1000 km north of the generally accepted northern limit of summer thermal stratification. Given their location approaching the northernmost land on Earth, the thermal profiles of these lakes suggest that the occurrence of summer stratification may no longer be discounted anywhere in the Northern Hemisphere.
Constraints on primordial black holes in the mixed dark matter scenarios using the ratio $$\mathrm (^3{He}+D)/H$$
Authors: Yang Yupeng , Li Xiujuan , Li Gang 
Published: October 2023

AbstractWe derive the upper limit on the dark matter (DM) fraction in primordial black holes (PBHs) in the mixed DM scenarios. In this scenarios, a PBH can accrete weakly interacting massive particles (WIMPs) to form a ultracompact minihalo (UCMH) with a density profile of $$\rho _{\textrm{DM}}(r)\sim r^{-9/4}$$

ρ
DM

(
r
)

∼

r

-
9
/
4

. The energy released from UCMHs due to dark matter annihilation has influence on the photodissociation of $$^{4}{\textrm{He}}$$

4

He

, producing the $$^{3}{\textrm{He}}$$

3

He

and the D. By requiring that the ratio $$(^3\text {He}+\text {D})/\text {H}$$

(
3

He
+
D
)
/
H

caused by UCMHs does not exceed the measured value, we derive the upper limit on the dark matter fraction in PBHs. For the canonical value of DM thermally averaged annihilation cross section $$\left<\sigma v\right>=3\times 10^{-26}\text {cm}^{3}\,\text {s}^{-1}$$

σ
v

=
3
×

10

-
26

cm
3

s

-
1

, we find that the upper limit is $$f_{\textrm{PBH}} < 0.35(0.75)$$

f
PBH

<
0.35

(
0.75
)

for DM mass $$m_{\chi }=1(10)~ \text {GeV}$$

m
χ

=
1

(
10
)

GeV

. Compared with other limits obtained by different astronomical measurements, although our limit is not the strongest, we provide a different way of constraining the cosmological abundance of PBHs.
Continuing WebAssembly with Effect Handlers
Authors: Phipps-Costin Luna , Rossberg Andreas , Guha Arjun , Leijen Daan , Hillerström Daniel , Sivaramakrishnan KC , Pretnar Matija , Lindley Sam 
Published: October 2023

WebAssembly (Wasm) is a low-level portable code format offering near
native performance. It is intended as a compilation target for a wide
variety of source languages. However, Wasm provides no direct support
for non-local control flow features such as async/await,
generators/iterators, lightweight threads, first-class continuations,
etc. This means that compilers for source languages with such features
must ceremoniously transform whole source programs in order to target
Wasm.
We present WasmFX an extension to Wasm which provides a universal
target for non-local control features via effect handlers, enabling
compilers to translate such features directly into Wasm. Our
extension is minimal and only adds three main instructions for
creating, suspending, and resuming continuations. Moreover, our
primitive instructions are type-safe providing typed continuations
which are well-aligned with the design principles of Wasm whose stacks
are typed. We present a formal specification of WasmFX and show that
the extension is sound. We have implemented WasmFX as an extension to
the Wasm reference interpreter and also built a prototype WasmFX
extension for Wasmtime, a production-grade Wasm engine, piggybacking
on Wasmtime's existing fibers API. The preliminary performance
results for our prototype are encouraging, and we outline future plans
to realise a native implementation.
Adventure of a Lifetime: Extract Method Refactoring for Rust
Authors: Thy Sewen , Costea Andreea , Gopinathan Kiran , Sergey Ilya 
Published: October 2023

We present a design and implementation of the automated "Extract Method" refactoring for Rust programs. Even though Extract Method is one of the most well-studied and widely used in practice automated refactorings, featured in all major IDEs for all popular programming languages, implementing it soundly for Rust is surprisingly non-trivial due to the restrictions of the Rust's ownership and lifetime-based type system.
In this work, we provide a systematic decomposition of the Extract Method refactoring for Rust programs into a series of program transformations, each concerned with satisfying a particular aspect of Rust type safety, eventually producing a well-typed Rust program. Our key discovery is the formulation of Extract Method as a composition of naive function hoisting and a series of automated program repair procedures that progressively make the resulting program "more well-typed" by relying on the corresponding repair oracles. Those oracles include a novel static intra-procedural ownership analysis that infers correct sharing annotations for the extracted function's parameters, and the lifetime checker of rustc, Rust's reference compiler.
We implemented our approach in a tool called REM---an automated Extract Method refactoring built on top of IntelliJ IDEA plugin for Rust. Our extensive evaluation on a corpus of changes in five popular Rust projects shows that REM (a) can extract a larger class of feature-rich code fragments into semantically correct functions than other existing refactoring tools, (b) can reproduce method extractions performed manually by human developers in the past, and (c) is efficient enough to be used in interactive development.
From Capabilities to Regions: Enabling Efficient Compilation of Lexical Effect Handlers
Authors: Müller Marius , Schuster Philipp , Starup Jonathan Lindegaard , Ostermann Klaus , Brachthäuser Jonathan Immanuel 
Published: October 2023

Effect handlers are a high-level abstraction that enables programmers to use effects in a structured
way. They have gained a lot of popularity within academia and subsequently also in industry. However,
the abstraction often comes with a significant runtime cost and there has been intensive research
recently on how to reduce this price.
A promising approach in this regard is to implement effect handlers using a CPS translation and
to provide sufficient information about the nesting of handlers. With this information the
CPS translation can decide how effects have to be lifted through handlers, i.e., which handlers
need to be skipped, in order to handle the effect at the correct place. A structured way to make
this information available is to use a calculus with a region system and explicit subregion
evidence. Such calculi, however, are quite verbose, which makes them impractical to use as a
source-level language.
We present a method to infer the lifting information for a calculus underlying a source-level language.
This calculus uses second-class capabilities for the safe use of effects. To do so, we define a typed translation
to a calculus with regions and evidence and we show that this lift-inference translation is typability-
and semantics-preserving. On the one hand, this exposes the precise relation between the second-class
property and the structure given by regions. On the other hand, it closes a gap in a compiler pipeline
enabling efficient compilation of the source-level language. We have implemented lift inference in this
compiler pipeline and conducted benchmarks which indicate that the approach is indeed working.
Etiology of Primary Cerebellar Intracerebral Hemorrhage Based on Topographic Localization
Authors: Incontri Diego , Marchina Sarah , Andreev Alexander , Wilson Mitchell , Wang Jia-Yi , Lin David , Heistand Elizabeth C. , Carvalho Filipa , Selim Magdy , Lioutas Vasileios-Arsenios 
Published: October 2023

BACKGROUND:
Cerebellar intracerebral hemorrhage (cICH) is often attributed to hypertension or cerebral amyloid angiopathy (CAA). However, deciphering the exact etiology can be challenging. A recent study reported a topographical etiologic relationship with superficial cICH secondary to CAA. We aimed to reexamine this relationship between topography and etiology in a separate cohort of patients and using the most recent Boston criteria version 2.0.

METHODS:
We performed a retrospective analysis of consecutive patients with primary cICH admitted to a tertiary academic center between 2000 and 2022. cICH location on brain computed tomography/magnetic resonance imaging scan(s) was divided into strictly superficial (cortex, surrounding white matter, vermis) versus deep (cerebellar nuclei, deep white matter, peduncular region) or mixed (both regions). Magnetic resonance imaging was rated for markers of cerebral small vessel disease. We assigned possible/probable versus absent CAA using Boston criteria 2.0.

RESULTS:

We included 197 patients; 106 (53.8%) were females, median age was 74 (63–82) years. Fifty-six (28%) patients had superficial cICH and 141 (72%) deep/mixed cICH. Magnetic resonance imaging was available for 112 (57%) patients (30 [26.8%] with superficial and 82 [73.2%] with deep/mixed cICH). Patients with superficial cICH were more likely to have possible/probable CAA (48.3% versus 8.6%; odds ratio [OR], 11.43 [95% CI, 3.26–40.05];
P
<0.001), strictly lobar cerebral microbleeds (51.7% versus 6.2%; OR, 14.18 [95% CI, 3.98–50.50];
P
<0.001), and cortical superficial siderosis (13.8% versus 1.2%; OR, 7.70 [95% CI, 0.73–80.49];
P
=0.08). Patients with deep/mixed cICH were more likely to have deep/mixed cerebral microbleeds (59.2% versus 3.4%; OR, 41.39 [95% CI, 5.01–341.68];
P
=0.001), lacunes (54.9% versus 17.2%; OR, 6.14 [95% CI, 1.89–19.91];
P
=0.002), severe basal ganglia enlarged perivascular spaces (36.6% versus 7.1%; OR, 7.63 [95% CI, 1.58–36.73];
P
=0.01), hypertension (84.4% versus 62.5%; OR, 3.43 [95% CI, 1.61 to −7.30];
P
=0.001), and higher admission systolic blood pressure (172 [146–200] versus 146 [124–158] mm Hg,
P
<0.001).

CONCLUSIONS:
Our results suggest that superficial cICH is strongly associated with CAA whereas deep/mixed cICH is strongly associated with hypertensive arteriopathy.
Generalized Low-Rank Update: Model Parameter Bounds for Low-Rank Training Data Modifications
Authors: Hanada Hiroyuki , Hashimoto Noriaki , Taji Kouichi , Takeuchi Ichiro 
Published: October 2023

Abstract
In this study, we have developed an incremental machine learning (ML) method that efficiently obtains the optimal model when a small number of instances or features are added or removed. This problem holds practical importance in model selection, such as cross-validation (CV) and feature selection. Among the class of ML methods known as linear estimators, there exists an efficient model update framework, the low-rank update, that can effectively handle changes in a small number of rows and columns within the data matrix. However, for ML methods beyond linear estimators, there is currently no comprehensive framework available to obtain knowledge about the updated solution within a specific computational complexity. In light of this, our study introduces a the generalized low-rank update (GLRU) method, which extends the low-rank update framework of linear estimators to ML methods formulated as a certain class of regularized empirical risk minimization, including commonly used methods such as support vector machines and logistic regression. The proposed GLRU method not only expands the range of its applicability but also provides information about the updated solutions with a computational complexity proportional to the number of data set changes. To demonstrate the effectiveness of the GLRU method, we conduct experiments showcasing its efficiency in performing cross-validation and feature selection compared to other baseline methods.
Ubiquitous Sea Surface Temperature Anomalies Increase Spatial Heterogeneity of Trade Wind Cloudiness on Daily Time Scale
Authors: Chen Xuanyu , Dias Juliana , Wolding Brandon , Pincus Robert , DeMott Charlotte , Wick Gary , Thompson Elizabeth J. , Fairall Chris W. 
Published: October 2023

Abstract
The impact of weak submeso- to mesoscale SST anomalies on daily averaged trade cumulus cloudiness is investigated using satellite observations that have been validated against shipboard measurements from the Atlantic Tradewind Ocean–Atmosphere Mesoscale Interaction Campaign (ATOMIC). Daily spatial SST anomalies are identified from GOES–POES Blended SST analysis within a 10° × 10° region during January and February 2020. Daily averaged cloud fraction and 10-m neutral wind from satellite observations and reanalysis are composited over the identified SST features, using a common coordinate system based on the near-surface background wind directions. Composites of satellite cloud fraction show a statistically significant increase of cloudiness over the SST warm core with a reduction of cloudiness away from it. These responses are largely the same but with opposite signs over SST cold anomalies, suggesting that spatial heterogeneity in SST can locally imprint on daily cloud fraction. Composites of daily 10-m wind speed and wind convergence anomalies from both satellite and reanalysis show that surface wind speed is increased over SST warm anomalies, implying enhanced turbulence over warmer SSTs. Correspondingly, the surface convergence anomalies in these composites are located around the maximum downwind SST gradient, offset downwind from the cloudiness anomalies. These results indicate that the response of daily cloudiness to these SST anomalies is more likely generated by spatial variability of surface-driven turbulence and surface fluxes rather than that of surface or boundary layer convergence.
Geopsychiatry and geography: A response
Authors: Philo Chris , Callard Felicity , McGeachan Cheryl , Parr Hester 
Published: October 2023

Background: This contribution responds to three articles (we refer to all three as ‘editorials’) concerning something called ‘geopsychiatry’. Aims: To evaluate claims made in these editorials for ‘geopsychiatry’ as a new field of inquiry at the interface between geography and psychiatry. Method: Close critical reading of two editorials in the International Journal of Social Psychiatry – entitled ‘Geographical determinants of mental health’ and ‘Political determinants of mental health’ – and one in the International Review of Psychiatry – entitled ‘What is geopsychiatry?’ Results: While this geopsychiatry initiative is to be applauded, disquiet can be expressed about the almost complete neglect of a pre-existing domain of inquiry – ‘mental health geography’ or ‘the geography of mental health’ – that has long been researched by academic geographers and cognate scholars. Key trajectories in this field can be identified and related to the proposed foci for geopsychiatry. Conclusions: The hope is voiced that future developments in geopsychiatry will proceed in dialogue with the literature and practitioners of mental health geography.
An epidemiological survey on personality disorder in Andalusia (the PISMA-ep PD study)
Authors: Muñoz-Negro José Eduardo , Gutiérrez Blanca , Rivera Margarita , Molina Esther , González Díez Manuel , Jabalera Ruz Paula , Cervilla Jorge A. 
Published: October 2023

Background: Despite a significant clinical and social burden, there is a relative scarcity of epidemiological studies on Personality Disorder (PD). Aim: To determine the current prevalence of PD and the psychosocial correlates associated with this in the Andalusian population. Method: We carried out a cross-sectional population mental-health survey in Andalusia, southern Spain. Thus, 4,518 randomly selected participants were interviewed following sampling using different standard stratification levels. We used the Spanish version of the SAPAS to estimate PD prevalence. In addition, a full battery of other instruments was utilized to explore global functionality, childhood abuse, maltreatment, threatening life events, personality traits (neuroticism, impulsivity and paranoia), medical and psychiatric comorbidities, family history of psychological problems and other potential risk factors for PD. Results: PD prevalence (10.8%; 95% CI [9.8, 11.7]) and ran two different multivariate models for PD. We obtained the highest PD prevalence in those affected by any mental disorder plus those reporting having suffered childhood abuse, particularly sexual abuse. Additional potential risk factors or correlates of PD identified were: younger age, lower levels of functioning, less social support, poorer general health, having suffered maltreatment, threatening life events, higher suicidal risk scores and higher levels of both neuroticism and impulsivity. Conclusions: This study reports PD prevalence and risk correlates in consonance with similar findings reported in other Western populations. However, longitudinal studies are needed to elicit a more thorough group of prospective determinants of PD.