bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 omicron spike simulations: broad antibody escape, weakened ACE2 binding, and modest furin cleavage
Authors: Jawaid M. Zaki , Baidya A. , Mahboubi-Ardakani R. , Davis Richard L. , Cox Daniel L. 
Published: August 2023

ABSTRACT
The recent emergence of the omicron variant of the SARS-CoV-2 virus with large numbers of mutations has raised concern about a potential new surge in infections. Here we use molecular dynamics to study the biophysics of the interface of the BA1 and BA2 omicron spike protein binding to (i) the ACE2 receptor protein, (ii) antibodies from all known binding regions, and (iii) the furin binding domain. Our simulations suggest that while there is a significant reduction of antibody (Ab) binding strength corresponding to escape, the omicron spikes pay a cost in terms of weaker receptor binding as measured by interfacial hydrogen bonds (H-bond). The furin cleavage domain (FCD) is the same or weaker binding than the delta variant, suggesting lower fusogenicity resulting in less viral load and disease intensity than the delta variant.

IMPORTANCE

The BA1 and BA2 and closely related BA2.12.2 and BA.5 omicron variants of SARS-CoV-2 dominate the current global infection landscape. Given the high number of mutations, particularly those which will lead to antibody escape, it is important to establish accurate methods that can guide developing health policy responses that identify at a fundamental level whether omicron and its variants are more threatening than its predecessors, especially delta. The importance of our work is to demonstrate that simple
in silico
simulations can predict biochemical binding details of the omicron spike protein that have epidemiological consequences, especially for binding to the cells and for fusing the viral membrane with the cells. In each case, we predicted weaker binding of the omicron spike, which agreed with subsequent experimental results. Future virology experiments will be needed to test these predictions further.
Evaluation of vitamin B6supplementation in Wilson’s disease patients treated with D-penicillamine
Authors: Mbala Justin , Belmalih Abdelouahed , Guillaud Olivier , Lachaux Alain , Couchonnal Bedoya Eduardo 
Published: August 2023

IntroductionWilson’s disease (WD) is a copper metabolism disorder characterised by a progressive accumulation of this metal mainly in the liver and the brain. Treatment is based on the removal of copper operated by the chelators, among which, D-penicillamine (DP) is prescribed as a first-line treatment in most situations. There is some evidence in linking the use of DP with a risk of vitamin B6; therefore, vitamin supplementation is sometimes recommended, although non-consensually. The objective of our study was to evaluate the level of vitamin B6in WD patients treated with DP with and without associated supplementation.MethodologyAll WD patients followed at the National Reference Centre for WD in Lyon between January 2019 and December 2020 treated with DP for more than 1 year were included and separated in two groups according to vitamin B6supplementation. The level of vitamin B6was measured by the determination of pyridoxal phosphate (PLP).ResultsA total of 37 patients were included. Average age of 23.3±14.8 years, 15 patients with <18 years. Median duration of treatment was 51 (55.8) months. 15 patients were under vitamin B6supplementation and 22 had interrupted it for more than 1 year. The median PLP level was significantly higher in the group with supplementation, 137.2 (86.7) nmol/L vs 64.9 (30.8) nmol/(p<0.01). No patient had a PLP level<35 nmol/L.ConclusionLong-term stable WD patients under DP treatment probably do not need vitamin B6supplementation.
Expanding community pharmacists’ scope of practice in relation to contraceptive counselling and referral: a protocol for a pragmatic, stepped-wedge, cluster randomised trial (ALLIANCE)
Authors: Mazza Danielle , Assifi Anisa Rojanapenkul , Hussainy Safeera Yasmeen , Bateson Deborah , Johnston Stefanie , Tomnay Jane , Kasza Jessica , Church Jody , Grzeskowiak Luke E , Nissen Lisa , Cameron Sharon Tracey 
Published: August 2023

IntroductionImproving access to effective contraception has the potential to reduce unintended pregnancy and abortion rates. Community pharmacists could play an expanded role in contraceptive counselling and referral to contraceptive prescribers particularly when women are already attending community pharmacy to obtain emergency contraceptive pills (ECPs) or to have medical abortion (MA) medicines dispensed. The ALLIANCE trial aims to compare the subsequent uptake of effective contraception (hormonal or intrauterine) in women seeking ECP or MA medicines, who receive the ALLIANCE community pharmacy-based intervention with those who do not receive the intervention.Methods and analysisALLIANCE is a stepped-wedge pragmatic cluster randomised trial in Australian community pharmacies. The ALLIANCE intervention involves community pharmacists delivering structured, patient-centred, effectiveness-based contraceptive counselling (and a referral to a contraceptive prescriber where appropriate) to women seeking either ECPs or to have MA medicines dispensed. Women participants will be recruited by participating pharmacists. A total of 37 pharmacies and 1554 participants will be recruited. Pharmacies commence in the control phase and are randomised to transition to the intervention phase at different time points (steps). The primary outcome is the self-reported use of effective contraception at 4 months; secondary outcomes include use of effective contraception and the rate of pregnancies or induced abortions at 12 months. A process and economic evaluation of the trial will also be undertaken.Ethics and disseminationEthical approval has been obtained from the Monash University Human Research Ethics Committee (#34563). An explanatory statement will be provided and written consent will be obtained from all participants (pharmacy owner, pharmacist and women) before their commencement in the trial. Dissemination will occur through a knowledge exchange workshop, peer-reviewed journal publications, presentations, social media and conferences.Trial registration numberACTRN12622001024730.
Basilar artery occlusion location and clinical outcome: data from the ATTENTION multicenter registry
Authors: Yu Shuai , Wang Xiaocui , Guo Zhiliang , Xu Pengfei , Tao Chunrong , Li Rui , Hu Wei , Xiao Guodong 
Published: August 2023

BackgroundAcute basilar artery occlusion is a disabling and life-threatening condition. The purpose of this study was to evaluate the impact of occluded vessel location on the prognostic outcomes of patients who underwent endovascular treatment for acute basilar artery occlusion.MethodsPatient data for this study were obtained from the ATTENTION registry. Baseline data of the patients were described and compared across different occlusion locations. Univariable and multivariable regression analyses were performed to assess the effect of occluded vessel location on associated prognostic outcomes.ResultsA total of 1672 patients were included in the analysis, with 583 having distal occlusion, 540 having middle occlusion, and 549 having proximal occlusion. Unlike distal occlusion, both proximal and middle occlusions were significantly and negatively associated with favorable clinical outcomes (for modified Rankin Scale score 0–3: adjusted odds ratio (aOR) 0.634, 95% confidence interval (95% CI) 0.493 to 0.816, P<0.001 in middle occlusion, and aOR 0.620, 95% CI 0.479 to 0.802, P<0.001 in proximal occlusion). Mortality was higher in patients with proximal and middle occlusions (aOR 1.461, 95% CI 1.123 to 1.902, P=0.005 in middle occlusion, and aOR 1.648, 95% CI 1.265 to 2.147, P<0.001 in proximal occlusion). The occluded vessel location was not associated with symptomatic intracranial hemorrhage.ConclusionsProximal and middle basilar artery occlusions were predominantly associated with poor clinical outcomes and increased risk of death following endovascular treatment.
Developing evidence-based patient-focused learning materials to support health behaviour change for people living with psoriatic arthritis
Authors: Hailey Louise , Howells Laura , Bundy Christine , Kirtley Shona , Martin Samantha , O'Sullivan Denis , Steinkoening Ingrid , Stepney Melissa , Coates Laura C 
Published: August 2023

ObjectivesIn psoriatic arthritis (PsA), self-management is important for patient function and quality of life. Behaviour change can be difficult, patients could benefit from high-quality support to initiate change. Our aim was to codesign the project as theory-informed, evidence-based, patient-focused, materials supporting healthy lifestyle changes for patients diagnosed with PsA.MethodsDevelopment of the materials was overseen by a steering group of patients with PsA, psychologists, rheumatologists, a design team and researchers. First, a literature review was performed to establish the evidence base for behaviours and potential interventions in PsA, including diet, weight, alcohol, smoking, exercise, anxiety, depression and stress. An initial roundtable of patients with PsA prioritised areas and content ideas. Draft materials including a website and downloadable materials were produced. A second roundtable of patients with PsA collected feedback on the draft content and design. A third roundtable was held with patients with PsA and a fourth with clinicians to refine the materials and ensuring that they were evidence based, accessible, interesting, and helpful to initiate and maintain change. A final evaluation survey was performed to review the draft website before launching the final materials.Results15 candidate topics were prioritised. A website and set of postcards summarising the topics were developed by the design team and refined following feedback from the roundtable groups.ConclusionThis project created patient-focused resources to support behaviour change. It addresses common concerns of patients with PsA about how they may optimise their health by providing practical and brief interventions to challenge and support them to make changes.
Phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group study of ustekinumab in Japanese patients with active polymyositis and dermatomyositis who have not adequately responded to one or more standard-of-care treatments
Authors: Kawahata Kimito , Ishii Tomonori , Gono Takahisa , Tsuchiya Yumi , Ohashi Hiroki , Yoshizawa Katsunori , Zheng Richuan , Ayabe Maori , Nishikawa Kazuko 
Published: August 2023

ObjectivesTo evaluate the efficacy and safety of ustekinumab (UST) in a multicentre, randomised, double-blind, placebo-controlled trial in adult Japanese patients with active polymyositis (PM) and dermatomyositis (DM).MethodsFifty-one Japanese adults diagnosed with active PM/DM who did not respond adequately to one or more standard-of-care treatments were randomised 1:1 to receive UST (n=25) or placebo (n=26). Participants received body weight-range based intravenous administration of UST (6 mg/kg) or placebo at week 0 followed by 90 mg subcutaneous (SC) administration of UST or placebo every 8 weeks from week 8 to week 24. At week 24, placebo group crossed over to receive body weight-range based intravenous administration of UST, and thereafter, all participants received/were to receive SC administration of UST 90 mg every 8 weeks (week 32 through to week 72). The primary efficacy endpoint was the proportion of participants who achieved minimal improvement (≥20) in the International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) at week 24.ResultsNo statistically significant difference was seen in the proportion of participants who achieved minimal improvement (≥20) in IMACS TIS at week 24 between the treatment groups (UST 64.0% vs placebo 61.5%, p=0.94) based on the primary estimand of the primary endpoint analysis.ConclusionsUST was safe and well tolerated but did not meet the primary efficacy endpoint in adult Japanese participants with active PM/DM based on the primary analysis at week 24 in the study.Trial registration numberNCT03981744.
Preconception clinical factors related to adverse pregnancy outcomes in patients with systemic lupus erythematosus or primary Sjögren’s syndrome: a retrospective cohort study
Authors: Fierro Juan J. , Prins Jelmer R. , Verstappen Gwenny M. , Bootsma Hendrika , Westra Johanna , de Leeuw Karina 
Published: August 2023

ObjectiveTo identify preconception clinical factors associated with adverse pregnancy outcomes (APO) in patients with systemic lupus erythematosus (SLE) or primary Sjögren’s syndrome (pSS).MethodsA single-centre, retrospective cohort study was conducted, which included pregnant women treated at the University Medical Center Groningen between January 2010 and August 2021 who fulfilled classification criteria for SLE or pSS. Demographic data, relevant comorbidities, disease duration, disease activity before and during pregnancy, APO, laboratory parameters and treatment regimens were recorded. Associations between the presence of APO and preconception characteristics were evaluated.ResultsOur study population included 48 (70%) SLE and 21 (30%) pSS pregnancies concerning 70 fetuses (one twin). Preterm birth (n=9, 19%) was the most frequent APO in SLE pregnancies, while in pSS pregnancies this was miscarriages (n=3, 14%). There were no associations between the presence of APO in SLE pregnancies and clinical parameters, laboratory parameters or medication use prior to conception. In the pSS group, significant associations were found between the presence of APO and body mass index (p=0.010), parity (p=0.046), C4 (p=0.021) and low C4 levels (p=0.002).ConclusionsNo preconception risk factors related to APO were found in SLE pregnancies, whereas preconception complement levels were associated with APO development in patients with pSS.
Infinite collision property for the three-dimensional uniform spanning tree
Authors: Watanabe Satomi 
Published: August 2023

Let [Formula: see text] be the three-dimensional uniform spanning tree, whose probability law is denoted by [Formula: see text]. For [Formula: see text]-a.s. realization of [Formula: see text], the recurrence of the simple random walk on [Formula: see text] is proved in Benjamini et al. (2001) [I. Benjamini, R. Lyons, Y. Peres and O. Schramm, Uniform spanning forests, Ann. Probab. 29(1) (2001) 1–65] and it is also demonstrated in Hutchcroft and Peres (2015) [T. Hutchcroft and Y. Peres, Collisions of random walks in reversible random graphs, Electron. Commun. Probab. 20(63) (2015) 1–6] that two independent simple random walks on [Formula: see text] collide infinitely often. In this paper, we will give a quantitative estimate on the number of collisions of two independent simple random walks on [Formula: see text], which provides another proof of the infinite collision property of [Formula: see text].
Reflecting on Random Generation
Authors: Goldstein Harrison , Frohlich Samantha , Wang Meng , Pierce Benjamin C. 
Published: August 2023

Expert users of property-based testing often labor to craft random generators that encode detailed knowledge about what it means for a test input to be valid and interesting. Fortunately, the fruits of this labor can also be put to other uses. In the bidirectional programming literature, for example, generators have been repurposed as validity checkers, while Python's Hypothesis library uses the same structures for shrinking and mutating test inputs.
To unify and generalize these uses and many others, we propose reflective generators, a new foundation for random data generators that can "reflect" on an input value to calculate the random choices that could have been made to produce it. Reflective generators combine ideas from two existing abstractions: free generators and partial monadic profunctors. They can be used to implement and enhance the aforementioned shrinking and mutation algorithms, generalizing them to work for any values that can be produced by the generator, not just ones for which a trace of the generator's execution is available. Beyond shrinking and mutation, reflective generators generalize a published algorithm for example-based generation, and they can also be used as checkers, partial value completers, and other kinds of test data producers.
Intrinsically Typed Sessions with Callbacks (Functional Pearl)
Authors: Thiemann Peter 
Published: August 2023

All formalizations of session types rely on linear types for soundness as
session-typed communication channels must change their type at every
operation. Embedded language implementations of session types follow
suit. They either rely on clever typing constructions to guarantee
linearity statically, or on run-time checks that approximate
linearity.
We present a new language-embedded implementation of session types,
which is inspired by the inversion-of-control design principle. With
our approach, all application programs are intrinsically session-typed and
unable to break linearity by construction. Our design relies on a tiny
encapsulated library, for which linearity remains a proof
obligation that can be discharged once and for all when the library is built.
We demonstrate that our proposed design extends to a wide range of
features of session type systems: branching, recursion, multichannel
and higher-order sessions, as well as context-free sessions. The
multichannel extension provides an embedded implementation of
session types which guarantees deadlock freedom by construction.
The development reported in this paper is fully backed by
type-checked Agda code.
Global Existence and Decaying Rates of the Strong Solution for the Boussinesq System
Authors: Wang Lu , Yan Shuokai , Zhang Qinghua 
Published: August 2023

This paper focuses on the global existence and time-decay rates of the strong solution for the Boussinesq system with full viscosity in

R

n

for

n
≥
3

. Under the initial assumption of

θ

0

,

u

0

∈

L

n
/
3

×

L

n

with a small norm, and

n
>
3

or

n
=
3

and

θ

0

∈

L

r

0

for some

r

0

>
1

, global existence and uniqueness of the strong solution

θ
,
u

for the Boussinesq system is established. This solution is proven to obey the following estimates:

θ

t

r

≤
C

t

−

3
−
n
/
p

/
2

for

n
/
3
≤
p
<
∞

,

u

t

p

≤
C

t

−

1
−
n
/
q

/
2

for

n
≤
q
≤
∞

,

∇
θ

t

p

≤
C

t

−

3
−
n
/
p

/
2
−
1
/
2

and

∇

2

θ

t

p

=
O

t

−
n

1
/
r
−
1
/
p

/
2
−
1

as

t
⟶
∞

for

r
≤
p
<
n
/
2

, and

∇
u

t

q

≤
C

t

−

1
−
n
/
q

/
2
−
1
/
2

and

∇

2

u

t

q

=
O

t

−
n

1
/
r
−
1
/
q

/
2
−
1

as

t
⟶
∞

for

n
≤
q
<
2
n

, where

r
=
n
/
3

if

n
>
3

and

1
<
r
<

min

r

0

,
n
/
2

if

n
=
3

.
Sequential Exposure to IL21 and IL15 During Human Natural Killer Cell Expansion Optimizes Yield and Function
Authors: Zhang Caimei , Kadu Siddhant , Xiao Yansen , Johnson Omar , Kelly Andre , O'Connor Roddy S. , Lai Meizan , Kong Hong , Srivatsa Sriram , Tai Victoria , Greenblatt Eli , Holmes Matthew , Riley James L. , June Carl H. , Sheppard Neil C. 
Published: August 2023

Abstract
Natural killer (NK) cells are frequently expanded for the clinic using irradiated, engineered K562 feeder cells expressing a core transgene set of membrane-bound (mb) IL15 and/or mbIL21 together with 41BBL. Prior comparisons of mbIL15 to mbIL21 for NK expansion lack comparisons of key attributes of the resulting NK cells, including their high-dimensional phenotype, polyfunctionality, the breadth and potency of cytotoxicity, cellular metabolism, and activity in xenograft tumor models. Moreover, despite multiple rounds of K562 stimulation, studies of sequential use of mbIL15- and mbIL21-based feeder cells are absent. We addressed these gaps and found that using mbIL15- versus mbIL21-based feeder cells drove distinct phenotypic and functional profiles. Feeder cells expressing mbIL15 alone drove superior functionality by nearly all measures, whereas those expressing mbIL21 alone drove superior yield. In combination, most attributes resembled those imparted by mbIL21, whereas in sequence, NK yield approximated that imparted by the first cytokine, and the phenotype, transcriptome, and function resembled that driven by the second cytokine, highlighting the plasticity of NK cell differentiation. The sequence mbIL21 followed by mbIL15 was advantageous in achieving significant yields of highly functional NK cells that demonstrated equivalent in vivo activity to those expanded by mbIL15 alone in two of three xenograft models. Our findings define the impact of mbIL15 versus mbIL21 during NK expansion and reveal a previously underappreciated tradeoff between NK yield and function for which sequential use of mbIL21-based followed by mbIL15-based feeder cells may be the optimal approach in many settings.
RNA-Binding Proteins Regulate Post-Transcriptional Responses to TGF-β to Coordinate Function and Mesenchymal Activation of Murine Endothelial Cells
Authors: Wardman Rhys , Keles Merve , Pachkiv Ihor , Hemanna Shruthi , Grein Steve , Schwarz Jennifer , Stein Frank , Ola Roxana , Dobreva Gergana , Hentze Matthias W. , Heineke Joerg 
Published: August 2023

BACKGROUND:
Endothelial cells (ECs) are primed to respond to various signaling cues. For example, TGF (transforming growth factor)-β has major effects on EC function and phenotype by driving ECs towards a more mesenchymal state (ie, triggering endothelial to mesenchymal activation), a dynamic process associated with cardiovascular diseases. Although transcriptional regulation triggered by TGF-β in ECs is well characterized, post-transcriptional regulatory mechanisms induced by TGF-β remain largely unknown.

METHODS:
Using RNA interactome capture, we identified global TGF-β driven changes in RNA-binding proteins in ECs. We investigated specific changes in the RNA-binding patterns of hnRNP H1 (heterogeneous nuclear ribonucleoprotein H1) and Csde1 (cold shock domain containing E1) using RNA immunoprecipitation and overlapped this with RNA-sequencing data after knockdown of either protein for functional insight. Using a modified proximity ligation assay, we visualized the specific interactions between hnRNP H1 and Csde1 and target RNAs in situ both in vitro and in mouse heart sections.

RESULTS:
Characterization of TGF-β–regulated RBPs (RNA-binding proteins) revealed hnRNP H1 and Csde1 as key regulators of the cellular response to TGF-β at the post-transcriptional level, with loss of either protein-promoting mesenchymal activation in ECs. We found that TGF-β drives an increase in binding of hnRNP H1 to its target RNAs, offsetting mesenchymal activation, but a decrease in Csde1 RNA-binding, facilitating this process. Both, hnRNP H1 and Csde1, dynamically bind and regulate specific subsets of mRNAs related to mesenchymal activation and endothelial function.

CONCLUSIONS:
Together, we show that RBPs play a key role in the endothelial response to TGF-β stimulation at the post-transcriptional level and that the RBPs hnRNP H1 and Csde1 serve to maintain EC function and counteract mesenchymal activation. We propose that TGF-β profoundly modifies RNA-protein interaction entailing feedback and feed-forward control at the post-transcriptional level, to fine-tune mesenchymal activation in ECs.