bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted long-read sequencing identifies missing pathogenic variants in unsolved Werner syndrome cases
Authors: Miller Danny E. , Lee Lin , Galey Miranda , Kandhaya-Pillai Renuka , Tischkowitz Marc , Amalnath Deepak , Vithlani Avadh , Yokote Koutaro , Kato Hisaya , Maezawa Yoshiro , Takada-Watanabe Aki , Takemoto Minoru , Martin George M. , Eichler Evan E. , Hisama Fuki M. , Oshima Junko 
Published: May 2022

BackgroundWerner syndrome (WS) is an autosomal recessive progeroid syndrome caused by variants inWRN. The International Registry of Werner Syndrome has identified biallelic pathogenic variants in 179/188 cases of classical WS. In the remaining nine cases, only one heterozygous pathogenic variant has been identified.MethodsTargeted long-read sequencing (T-LRS) on an Oxford Nanopore platform was used to search for a second pathogenic variant inWRN. Previously, T-LRS was successfully used to identify missing variants and analyse complex rearrangements.ResultsWe identified a second pathogenic variant in eight of nine unsolved WS cases. In five cases, T-LRS identified intronic splice variants that were confirmed by either RT-PCR or exon trapping to affect splicing; in one case, T-LRS identified a 339 kbp deletion, and in two cases, pathogenic missense variants. Phasing of long reads predicted all newly identified variants were on a different haplotype than the previously known variant. Finally, in one case, RT-PCR previously identified skipping of exon 20; however, T-LRS did not detect a pathogenic DNA sequence variant.ConclusionT-LRS is an effective method for identifying missing pathogenic variants. Although limitations with computational prediction algorithms can hinder the interpretation of variants, T-LRS is particularly effective in identifying intronic variants.
Effects of different light-emitting diode qualities on the growth and photosynthetic characteristics of Spathiphyllum floribundum
Authors: Song Yinglong , Shang Wenqian , Wang Zheng , He Songlin , Shi Liyun , Shen Yuxiao , Lou Xueyuan , Sun Yuke 
Published: May 2022

Spathiphyllum floribundum (Linden & André) N.E.Br. is an important indoor flower species. Thus, optimizing its growth by regulating the light quality under indoor low-light conditions may be critical for generating high-quality flowers. In this study, the effects of the following six light-quality treatments on peroxidase and superoxide dismutase activities in two S. floribundum cultivars (“Sweet Chico” and “Queen”) were analyzed: monochromatic light comprising 100% red (R, 657 nm) or 100% blue (B, 450 nm) light, a combination of R and B lights [80% R + 20% B (8:2), 70% R + 30% B (7:3), and 60% R + 40% B (6:4)], and white light. The light treatments were performed using light-emitting diodes. The light intensity and photoperiod were set to 45 ± 2 µmol·m−2·s−1 and 14 h·day−1, respectively. The results of this study revealed that an appropriate R:B light ratio may lead to increased pigment contents, thereby increasing the synthesis and accumulation of photosynthetic products, which will result in increased stress resistance and enhanced growth. These findings provide the basis for future investigations on the growth and production of S. floribundum and other indoor ornamental plants.
Kaon electromagnetic form factors in dispersion theory
Authors: Stamen D. , Hariharan D. , Hoferichter M. , Kubis B. , Stoffer P. 
Published: May 2022

AbstractThe electromagnetic form factors of charged and neutral kaons are strongly constrained by their low-energy singularities, in the isovector part from two-pion intermediate states and in the isoscalar contribution in terms of $$\omega $$
ω
and $$\phi $$
ϕ
residues. The former can be predicted using the respective $$\pi \pi \rightarrow {{\bar{K}}} K$$

π
π
→

K

¯

K

partial-wave amplitude and the pion electromagnetic form factor, while the latter parameters need to be determined from electromagnetic reactions involving kaons. We present a global analysis of time- and spacelike data that implements all of these constraints. The results enable manifold applications: kaon charge radii, elastic contributions to the kaon electromagnetic self energies and corrections to Dashen’s theorem, kaon boxes in hadronic light-by-light (HLbL) scattering, and the $$\phi $$
ϕ
region in hadronic vacuum polarization (HVP). Our main results are: $$\langle r^2\rangle _\text {c}=0.359(3)\,\text {fm}^2$$

⟨

r
2

⟩

c

=
0.359

(
3
)

fm
2

, $$\langle r^2\rangle _\text {n}=-0.060(4)\,\text {fm}^2$$

⟨

r
2

⟩

n

=
-
0.060

(
4
)

fm
2

for the charged and neutral radii, $$\epsilon =0.63(40)$$

ϵ
=
0.63
(
40
)

for the elastic contribution to the violation of Dashen’s theorem, $$a_\mu ^{K\text {-box}}=-0.48(1)\times 10^{-11}$$

a
μ

K
-box

=
-
0.48

(
1
)

×

10

-
11

for the charged kaon box in HLbL scattering, and $$a_\mu ^\text {HVP}[K^+K^-, \le 1.05\,\text {GeV}]=184.5(2.0)\times 10^{-11}$$

a
μ
HVP

[

K
+

K
-

,
≤
1.05

GeV
]

=
184.5

(
2.0
)

×

10

-
11

, $$a_\mu ^\text {HVP}[K_SK_L, \le 1.05\,\text {GeV}]=118.3(1.5)\times 10^{-11}$$

a
μ
HVP

[

K
S

K
L

,
≤
1.05

GeV
]

=
118.3

(
1.5
)

×

10

-
11

for the HVP integrals around the $$\phi $$
ϕ
resonance. The global fit to $${{\bar{K}}} K$$

K

¯

K

gives $${{\bar{M}}}_\phi =1019.479(5)\,\text {MeV}$$

M

¯

ϕ

=
1019.479

(
5
)

MeV

, $${\bar{ \varGamma }}_\phi =4.207(8)\,\text {MeV}$$

Γ

¯

ϕ

=
4.207

(
8
)

MeV

for the $$\phi $$
ϕ
resonance parameters including vacuum-polarization effects.
Lorentzian path integral for quantum tunneling and WKB approximation for wave-function
Authors: Matsui Hiroki 
Published: May 2022

AbstractRecently, the Lorentzian path integral formulation using the Picard–Lefschetz theory has attracted much attention in quantum cosmology. In this paper, we analyze the tunneling amplitude in quantum mechanics by using the Lorentzian Picard–Lefschetz formulation and compare it with the WKB analysis of the conventional Schrödinger equation. We show that the Picard–Lefschetz Lorentzian formulation is consistent with the WKB approximation for wave-function and the Euclidean path integral formulation utilizing the solutions of the Euclidean constraint equation. We also consider some problems of this Lorentzian Picard–Lefschetz formulation and discuss a simpler semiclassical approximation of the Lorentzian path integral without integrating the lapse function.
Time and band-resolved scintillation in time projection chambers based on gaseous xenon
Authors: Leardini S. , García E. Sánchez , Amedo P. , Saa-Hernández A. , González-Díaz D. , Santorelli R. , Fernández-Posada D. J. , González D. 
Published: May 2022

AbstractWe present a systematic study of the time and band-resolved scintillation in xenon-based time projection chambers (TPCs), performed simultaneously for the primary (S1) and secondary (S2) components in a small, purity-controlled, setup. We explore a range of conditions of general academic interest, focusing on those of relevance to contemporary TPCs: pressure range 1–10 bar, pressure-reduced electric fields of 0–100 V/cm/bar in the drift region (S1) and up to the proportional scintillation regime in the multiplication region (S2), and wavelength bands 145–250/250–400/400–600 nm, for both$$\alpha $$αand$$\beta $$βparticles. Attention is paid to the possibility of non-conventional scintillation mechanisms such as the 3rd continuum emission, recombination light from$$\beta $$β-electrons at high pressure (for S1), emission from high-lying excited states and neutral bremsstrahlung (for S2). Time constants and, specially, scintillation yields have been obtained as a function of electric field and pressure, the latter aided by Geant4 simulations.
A chiral mean-field equation-of-state in UrQMD: effects on the heavy ion compression stage
Authors: Omana Kuttan Manjunath , Motornenko Anton , Steinheimer Jan , Stoecker Horst , Nara Yasushi , Bleicher Marcus 
Published: May 2022

AbstractIt is shown that the initial compression in central heavy ion collisions at beam energies of$$E_{\mathrm {lab}}=1-10A$$Elab=1-10A GeV depends dominantly on the underlying equation of state and only marginally on the model used for the dynamical description. To do so, a procedure to incorporate any equation of state in the UrQMD transport model is introduced. In particular we compare the baryon density, temperature and pressure evolution as well as produced entropy in a relativistic ideal hydrodynamics approach and the UrQMD transport model, where the same equation of state is used in both approaches. Not only is the compression similar if the same equation of state is used in either dynamical model, but it also strongly depends on the actual equation of state. These results indicate that the equation of state can be studied with observables which are sensitive to the initial compression phase and maximum compression achieved in heavy ion collisions at these beam energies.
Commutator subgroups of singular braid groups
Authors: Dey Soumya , Gongopadhyay Krishnendu 
Published: May 2022

The singular braids with [Formula: see text] strands, [Formula: see text], were introduced independently by Baez and Birman. It is known that the monoid formed by the singular braids is embedded in a group that is known as singular braid group, denoted by [Formula: see text]. There has been another generalization of braid groups, denoted by [Formula: see text], [Formula: see text], which was introduced by Fang as a group of symmetries behind quantum quasi-shuffle structures. The group [Formula: see text] simultaneously generalizes the classical braid group, as well as the virtual braid group on [Formula: see text] strands. We investigate the commutator subgroups [Formula: see text] and [Formula: see text] of these generalized braid groups. We prove that [Formula: see text] is finitely generated if and only if [Formula: see text], and [Formula: see text] is finitely generated if and only if [Formula: see text]. Further, we show that both [Formula: see text] and [Formula: see text] are perfect if and only if [Formula: see text].
TAG: Tagged Architecture Guide
Authors: Jero Samuel , Burow Nathan , Ward Bryan , Skowyra Richard , Khazan Roger , Shrobe Howard , Okhravi Hamed 
Published: May 2022

Software security defenses are routinely broken by the persistence of both security researchers and attackers. Hardware solutions based on tagging are emerging as a promising technique that provides strong security guarantees (e.g., memory safety) while incurring minimal runtime overheads and maintaining compatibility with existing codebases. Such schemes extend every word in memory with a tag and enforce security policies across them. This paper provides a survey of existing work on tagged architectures and describe the types of attacks such architectures aim to prevent as well as the guarantees they provide. It highlights the main distinguishing factors among tagged architectures and presents the diversity of designs and implementations that have been proposed. The survey reveals several real-world challenges have been neglected relating to both security and practical deployment. The challenges relate to the provisioning and enforcement phases of tagged architectures, and various overheads they incur. This work identifies these challenges as open research problems and provides suggestions for improving their security and practicality.
Design and Implementation of Hybrid Transmission Line Protection Scheme Using Signal Processing Techniques
Authors: Kumar Anup , Sharma Himanshu , Mahia Ram Niwash , Mahela Om Prakash , Khan Baseem 
Published: May 2022

A hybrid scheme for transmission line protection (HSTLP) using the Stockwell transform (ST), Wigner distribution function (WDF), and alienation coefficient (ACF) is designed. Current signals are analyzed using the ST, WDF, and ACF to compute the Stockwell fault index (SFI), Wigner fault index (WFI), and alienation coefficient fault index (ACFI), respectively. These fault indexes are used to derive a hybrid signal processing fault index (HSPFI), which is implemented for the detection of transmission line fault events. The peak magnitude of HSPFI is compared with a preset threshold magnitude (TH) to identify the fault. The statistical formulation is proposed for fault location on the power transmission line. Fault classification is achieved using the number of faulty phases. A hybrid ground fault index (HGFI) is used to recognize the involvement of the ground during the fault event. This HGFI is determined by processing zero sequence current using ST and WDF. The performance of algorithm is tested by various case studies for fault impedance variation, variable sampling frequency, fault incidence angle variation, reverse power flow on transmission line, highly loaded line, different fault locations online, and noisy conditions. The algorithm is also validated to detect a fault on a practical transmission line of large area utility grid of Rajasthan Rajya Vidyut Prasaran Nigam Limited (RVPN) in India. The algorithm performs better than the Hilbert–Huang transform (HHT)-based protection scheme and wavelet transform (WT)-based protection scheme available in the literature in terms of mean error of fault location, fault location accuracy, and noise level. The proposed protection scheme efficiently detected, classified, and located the faulty events such as single-phase-to-ground fault (SPGF), two-phase fault (TPF), two-phase-to-ground fault (TPGF), three-line fault (TLF), and three-line-to-ground fault (TLGF). Transmission line fault location accuracy of 99.031% is achieved. The algorithm performs well even with a high noise level of

10

dB

SNR.
Peptide PDHPS1 Inhibits Ovarian Cancer Growth through Disrupting YAP Signaling
Authors: Pan Xinxing , Geng Zhe , Li Jingyun , Li Xingxing , Zhang Mi , Wang Xusu , Cong Yu , Huang Ke , Xu Juan , Jia Xuemei 
Published: May 2022

Abstract
The lives of patients with ovarian cancer are threatened largely due to metastasis and drug resistance. Endogenous peptides attract increasing attention in oncologic therapeutic area, a few antitumor peptides have been approved by the FDA for clinical use over the past decades. However, only few peptides or peptide-derived drugs with antiovarian cancer effects have been identified. Here we focused on the biological roles and mechanism of a peptide named PDHPS1 in ovarian cancer development. Our results indicated that PDHPS1 reduced the proliferation ability of ovarian cancer cells in vitro and inhibited the ovarian cancer growth in vivo. Peptide pull down and following mass spectrometry, Western blot and qRT-PCR revealed that PDHPS1 could bind to protein phosphatase 2 phosphatase activator (PTPA), an essential activator of protein phosphatase 2A (PP2A), which resulted in increase of phosphorylated YAP, further inactivated YAP, and suppressed the expression of its downstream target genes. Flow cytometry, cell membrane permeability test, and IHC staining study demonstrated that there were no observable side effects of PDHPS1 on normal ovarian epithelium and hepatorenal function. Besides, modification of membrane penetration could improve the physicochemical properties and biological activity of PDHPS1. In conclusion, our study demonstrated that the endogenous peptide PDHPS1 serves as an antitumor peptide to inhibit YAP signaling pathway though interacting with PTPA in ovarian cancer.
Novel Markers for Liquid Biopsies in Cancer Management: Circulating Platelets and Extracellular Vesicles
Authors: Corvigno Sara , Johnson Anna Maria , Wong Kwong-Kwok , Cho Min Soon , Afshar-Kharghan Vahid , Menter David G. , Sood Anil K. 
Published: May 2022

Abstract
Although radiologic imaging and histologic assessment of tumor tissues are classic approaches for diagnosis and monitoring of treatment response, they have many limitations. These include challenges in distinguishing benign from malignant masses, difficult access to the tumor, high cost of the procedures, and tumor heterogeneity. In this setting, liquid biopsy has emerged as a potential alternative for both diagnostic and monitoring purposes. The approaches to liquid biopsy include cell-free DNA/circulating tumor DNA, long and micro noncoding RNAs, proteins/peptides, carbohydrates/lectins, lipids, and metabolites. Other approaches include detection and analysis of circulating tumor cells, extracellular vesicles, and tumor-activated platelets. Ultimately, reliable use of liquid biopsies requires bioinformatics and statistical integration of multiple datasets to achieve approval in a Clinical Laboratory Improvement Amendments setting. This review provides a balanced and critical assessment of recent discoveries regarding tumor-derived biomarkers in liquid biopsies along with the potential and pitfalls for cancer detection and longitudinal monitoring.
Longitudinal Undetectable Molecular Residual Disease Defines Potentially Cured Population in Localized Non–Small Cell Lung Cancer
Authors: Zhang Jia-Tao , Liu Si-Yang , Gao Wei , Liu Si-Yang Maggie , Yan Hong-Hong , Ji Liyan , Chen Yu , Gong Yuhua , Lu Hong-Lian , Lin Jun-Tao , Yin Kai , Jiang Ben-Yuan , Nie Qiang , Liao Ri-Qiang , Dong Song , Guan Yanfang , Dai Pingping , Zhang Xu-Chao , Yang Jin-Ji , Tu Hai-Yan , Xia Xuefeng , Yi Xin , Zhou Qing , Zhong Wen-Zhao , Yang Xue-Ning , Wu Yi-Long 
Published: May 2022

Abstract

The efficacy and potential limitations of molecular residual disease (MRD) detection urgently need to be fully elucidated in a larger population of non–small cell lung cancer (NSCLC). We enrolled 261 patients with stages I to III NSCLC who underwent definitive surgery, and 913 peripheral blood samples were successfully detected by MRD assay. Within the population, only six patients (3.2%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 96.8%. Longitudinal undetectable MRD may define the patients who were cured. The peak risk of developing detectable MRD was approximately 18 months after landmark detection. Correspondingly, the positive predictive value of longitudinal detectable MRD was 89.1%, with a median lead time of 3.4 months. However, brain-only recurrence was less commonly detected by MRD (n = 1/5, 20%). Further subgroup analyses revealed that patients with undetectable MRD might not benefit from adjuvant therapy. Together, these results expound the value of MRD in NSCLC.

Significance:
This study confirms the prognostic value of MRD detection in patients with NSCLC after definitive surgery, especially in those with longitudinal undetectable MRD, which might represent the potentially cured population regardless of stage and adjuvant therapy. Moreover, the risk of developing detectable MRD decreased stepwise after 18 months since landmark detection.
This article is highlighted in the In This Issue feature, p. 1599
Pathogenicity Assignment of Variants in Genes Associated With Cardiac Channelopathies Evolve Toward Diagnostic Uncertainty
Authors: Rosamilia Michael B. , Lu Isa M. , Landstrom Andrew P. 
Published: May 2022

Background:
Accurately determining variant pathogenicity is critical in the diagnosis of cardiac channelopathies; however, it remains unknown how variant pathogenicity status changes over time. Our aim is to use a comprehensive analysis of ClinVar to understand the mutability of variant evaluation in channelopathy-associated genes to inform clinical decision-making around variant calling.

Methods:

We identified 10 genes (
RYR2, CASQ2, KCNQ1, KCNH2, SCN5A, CACNA1C, CALM1, CALM2, CALM3, TRDN
) strongly associated with cardiac channelopathies, as well as 3 comparison gene sets (disputed long QT syndrome, sudden unexpected death in epilepsy, and all ClinVar). We comprehensively analyzed variant pathogenicity calls over time using the ClinVar database with Rstudio. Analyses focused on the frequency and directionality of clinically meaningful changes in disease association, defined as a change from one of the following three categories to another: likely benign/benign, conflicting evidence of pathogenicity/variant of uncertain significance, and likely pathogenic/pathogenic.

Results:

In total, among channelopathy-associated genes, there were 9975 variants in ClinVar and 8.4% had a clinically meaningful change in disease association at least once over the past 10 years, as opposed to 4.9% of all ClinVar variants. The 3 channelopathy-associated genes with the most variants undergoing a clinically significant change were
KCNQ1
(20.9%)
, SCN5A
(11.2%), and
KCNH2
(10.1%). Ten of the 12 included genes had variant evaluations that trended toward diagnostic uncertainty over time. Specifically, channelopathy-associated gene variants with either pathogenic/likely pathogenic or benign/likely benign assignments were 5.6× and 2×, respectively, as likely to be reevaluated to conflicting/variant of uncertain significance compared to the converse.

Conclusions:
Over the past 10 years, 8.4% of variants in channelopathy-associated genes have changed pathogenicity status with a decline in overall diagnostic certainty. Ongoing clinical and genetic variant follow-up is needed to account for presence of clinically meaningful change in variant pathogenicity assignment over time.
Pharmacogenomic Study of Statin-Associated Muscle Symptoms in the ODYSSEY OUTCOMES Trial
Authors: Murphy William A. , Lin Nan , Damask Amy , Schwartz Gregory G. , Steg P. Gabriel , Szarek Michael , Banerjee Poulabi , Fazio Sergio , Manvelian Garen , Pordy Robert , Shuldiner Alan R. , Paulding Charles 
Published: May 2022

Background:

Statin-associated muscle symptoms (SAMS) are the most frequently reported adverse events for statin therapies. Previous studies have reported an association between the p.Val174Ala missense variant in
SLCO1B1
and SAMS in simvastatin-treated subjects; however, evidence for genetic predictors of SAMS in atorvastatin- or rosuvastatin-treated subjects is currently lacking.

Methods:
ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; n=18 924) was a double-blind, randomized, placebo-controlled study evaluating the efficacy and safety of alirocumab (a PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitor) in acute coronary syndrome patients receiving high-intensity statin therapy. The goal of this pharmacogenomic analysis was to identify genetic variants associated with atorvastatin- and rosuvastatin-mediated SAMS among ODYSSEY OUTCOMES subjects who consented to participate in the genetic study (n=11 880). We performed multi-ancestry exome-wide and genome-wide association studies and gene burden analysis across 2 phenotypes (clinical SAMS [n=10 617] and creatine kinase levels [n=9630]).

Results:

A novel genome-wide significant association for an intronic variant (rs6667912) located within
TMEM9
(odds ratio [95% CI], 1.39 [1.24–1.55];
P
=3.71×10
−8
) for patients with clinical SAMS (cases=894, controls=9723) was identified. This variant is located ≈30 kb upstream of
CACNA1S
, a locus associated with severe SAMS. We replicated 2 loci, at
LINC0093
and
LILRB5
, previously associated with creatine kinase levels during statin treatment. No association was observed between p.Val174Ala (rs4149056) in
SLCO1B1
and SAMS (odds ratio [95% CI], 1.03 [0.90–1.18];
P
=0.69).

Conclusions:
This study comprises the largest discovery exome-wide and genome-wide association study for atorvastatin- or rosuvastatin-mediated SAMS to date. These novel genetic findings may provide biological/mechanistic insight into this drug-induced toxicity, and help identify at-risk patients before selection of lipid-lowering therapies.