bluuebunny/crossref_metadata_2025 huggingface dataset:
Convolutional modulation spectra of soliton molecular complexes in ultrafast laser
Authors: Zhao Qiuye , Zhang Yudong , Fang Zhen , Zhang Zuxing
Published: September 2023

Optical soliton molecules are common pulse states in dissipative system, and they can combine with each other to form soliton molecular complexes which exhibit cumbersome spectral characteristics. As there is an intrinsic connection between the spectra of the soliton molecules and soliton molecular complexes, we demonstrate that the spectra of soliton molecular complexes are the results of quadratic modulation between component solitons, through experimental verification and simulation analysis. Specifically, two strongly bound solitons modulate to form soliton molecules, and then the soliton molecules modulate with weakly bound soliton pairs to form soliton molecular complexes, which is called convolutional modulation. The results obtained have vital significance to better understanding of the intrinsic nature and interaction of the solitons. The formation of quadratic modulated spectra plays an inspiring role in the fields like modern fiber-optic communication systems, optical frequency combs and its related precision measurements and various practical applications.
Computer simulation of Fe epitaxial films on a Cu(100) substrate
Authors: Belim Sergey V , Tikhomirov Ilya V
Published: September 2023

The article addresses the problem of modeling thin epitaxial iron films on a Cu (100) substrate by calculating the surface potential. The purpose of the simulation is to determine the film structure. The model uses the paired Lennard-Jones potential to describe the interatomic interaction. We calculate the surface potential of the copper substrate using the first 10 surface atomic layers. The iron atoms in the first layer are placed in the minima of the surface potential. The surface potential of the monoatomic iron layer and the 9 copper layers underneath determine the position of the second iron layer. The position of atoms in the following layers is formed on the basis of similar calculations. Calculations show that the copper substrate stabilizes the fcc crystal lattice in the iron film at low temperatures. Bulk iron samples at low temperatures have a bcc crystal lattice. The period of the iron lattice along the substrate is equal to the period of the copper lattice. The crystal lattice period of iron perpendicular to the substrate has an intermediate value between the values for copper and for γ-ferrum. The interface effect causes additional vertical deformations in the first two layers of iron above the substrate.
Establishment of Justified Parameter Optimization Sequence for obtaining Maximum Solar Cell Efficiency
Authors: Bagade Sonal Santosh , Patel Shashidhar , Malik M M , Patel Piyush K
Published: September 2023

This paper questions the validity of t-NA/D-Nt technique for solar cell optimization and establishes the scientifically and experimentally-justified NA/D-Nt-t parameter optimization sequence for the same. Fundamental mathematical formulations considering numerous physical perspectives are presented for scientific justification of newly proposed optimization procedure. This is followed by an in-depth comprehensive analysis on sequence of parameter optimization applied in numerous widely-implemented solar cell fabrication techniques. It is found that, in each fabrication technique, the same optimization sequence of NA/D-Nt-t is implemented. Along with this, simulation study of sample solar cell is presented for further analysis of our conceptualization. It is identified that the time at which initial values of NA/D and Nt are replaced by the optimized ones to convert the initial solar cell to an optimized one, the value of absorber thickness at which solar cell produces maximum yield also changes. It was observed that NA/D-Nt-t optimization sequence increased device efficiency from 6.97% to 17.05% (144.6% increment) as compared to 55.8% increment from 6.97% to 10.86% in case of conventional t-NA/D-Nt optimization sequence. Moreover, only the NA/D-Nt-t approach produced EQE graph that matches with the experimentally-observed EQE curves of device. Hence, the newly proposed scientifically and experimentally-justified NA/D-Nt-t optimization sequence proposed for first time in this paper, truly optimizes solar cell device so that it offers maximum-possible efficiency reliably.
Probing massive neutrinos with the Minkowski functionals of the galaxy distribution
Authors: Liu Wei , Jiang Aoxiang , Fang Wenjuan
Published: September 2023

The characteristic signatures of massive neutrinos on large-scale structure (LSS), if
fully captured, can be used to put a stringent constraint on their mass sum, Mν
. Previous
work utilizing N-body simulations has shown the Minkowski functionals (MFs) of LSS can reveal the
imprints of massive neutrinos on LSS, provide important complementary information to two-point
statistics, and significantly improve constraints on Mν
. In this work, we take a step
forward and apply the statistics to the biased tracers of LSS, i.e. the galaxies, and in redshift
space. We perform a Fisher matrix analysis and quantify the constraining power of the MFs by using
the Molino mock galaxy catalogs, which are constructed based on the halo occupation distribution (HOD) framework with parameters for the SDSS Mr
< -21.5 and -22 galaxy samples. We find the MFs
give tighter constraints on all of the cosmological parameters that we consider than the power
spectrum. The constraints on Ωm, Ωb, h, ns
, σ
8, and
 Mν
from the MFs are better by a factor of 1.9, 2.9, 3.7, 4.2, 2.5, and 5.7, respectively,
after marginalizing over the HOD parameters. Specifically, for Mν
, we obtain a 1σ
8 
constraint of 0.059 eV with the MFs alone for a volume of only (1h
-1Gpc)3.
Influence of heat treatment on microstructure, mechanical and corrosion behavior of WE43 alloy fabricated by laser-beam powder bed fusion
Authors: Ling Chenrong , Li Qiang , Zhang Zhe , Yang Youwen , Zhou Wenhao , Chen Wenlong , Dong Zhi , Pan Chunrong , Shuai Cijun
Published: September 2023

Highlights

WE43 parts with favorable forming quality are fabricated by laser-beam powder bed fusion and the interaction between laser beam and powder is revealed.

After suitable heat treatment, the anisotropic microstructure is eliminated, with nano-scaled Mg24Y5 particles homogeneously precipitated.

The yield strength and ultimate tensile strength are improved to (250.2  ± 3.5)  MPa and (312  ± 3.7)  MPa, respectively, while the elongation still maintains at high level of 15.2%.

Homogenized microstructure inhibits the micro galvanic corrosion and promotes the development of passivation film, thus decreasing the degradation rate by an order of magnitude.

The porous WE43 scaffolds offer a favorable environment for cell growth.
Optimizing solidification process in phase change energy storage units with sinusoidal wave-shaped fins
Authors: Kumar Aman , Maurya Ambrish
Published: September 2023

Phase change energy storage units have attracted considerable interest in the field of energy storage technology. To overcome the challenge of low thermal conductivity associated with phase change material (PCM) employed in these units, researchers have implemented fins with various shapes. In this study, a two-dimensional numerical model of a phase change energy storage unit with newly designed sinusoidal wave-shaped fins is developed. The analysis is done using commercial software ANSYS-Fluent in the transient state. The solidification process of the PCM is evaluated with enthalpy–porosity method. The validation of the model is done against an experimental result from a published article. The study focused on increasing the surface area of sinusoidal wave-shaped fins, achieved by increasing its crests and troughs counts, and to analyse its impact on the solidification process of the PCM. The thermal performances are evaluated quantitatively by analysing the solidified portion of PCM, temperature distribution, rate of heat release, and velocity variation. The result shows that the total solidification time predicted for straight fin is 115.34 min. This duration reduces for wave-shaped fins, and it reduces even further as the crests and troughs counts of wave-shaped fins increases. The maximum reduction in total solidification time is observed as 19.93% for wave-shaped fin with 10 crests and troughs counts. It is also observed that rate of reduction in total solidification time initially decreases then marginally increases with the increase in crests or troughs counts. The effect of buoyancy on the PCM flow velocity is analysed at different locations within the phase change energy storage unit. It is observed that with the increase in crests and troughs counts the movement of PCM near the crest or trough decreases.
On the extended weight monoid of a spherical homogeneous space and its applications to spherical functions
Authors: Pezzini Guido , van Pruijssen Maarten
Published: September 2023

Given a connected simply connected semisimple group

G
G

and a connected spherical subgroup

K
⊆
G

K\subseteq G

we determine the generators of the extended weight monoid of

G

/

K

G/K

, based on the homogeneous spherical datum of

G

/

K

G/K

.

Let

H
⊆
G

H\subseteq G

be a reductive subgroup and let

P
⊆
H

P\subseteq H

be a parabolic subgroup for which

G

/

P

G/P

is spherical. A triple

(
G
,
H
,
P
)

(G,H,P)

with this property is called multiplicity free system and we determine the generators of the extended weight monoid of

G

/

P

G/P

explicitly in the cases where

(
G
,
H
)

(G,H)

is strictly indecomposable.

The extended weight monoid of

G

/

P

G/P

describes the induction from

H
H

to

G
G

of an irreducible

H
H

-representation

π
:
H
→
GL
⁡
(
V
)

\pi :H\to \operatorname {GL}(V)

whose lowest weight is a character of

P
P

. The space of regular

End
⁡
(
V
)

\operatorname {End}(V)

-valued functions on

G
G

that satisfy

F
(

h

1

g

h

2

)
=
π
(

h

1

)
F
(
g
)
π
(

h

2

)

F(h_{1}gh_{2})=\pi (h_{1})F(g)\pi (h_{2})

for all

h

1

,

h

2

∈
H

h_{1},h_{2}\in H

and all

g
∈
G

g\in G

is a module over the algebra of

H
H

-biinvariant regular functions on

G
G

. We show that under a mild assumption this module is freely and finitely generated. As a consequence the spherical functions of such a type

π
\pi

can be described as a family of vector-valued orthogonal polynomials with properties similar to Jacobi polynomials.
Constructing Residential Histories in a General Population-Based Representative Sample
Authors: Xu Wei , Agnew Megan , Kamis Christina , Schultz Amy , Salas Sarah , Malecki Kristen , Engelman Michal
Published: September 2023

Research on neighborhoods and health typically measures neighborhood context at a single point in time. However, neighborhood exposures accumulate over the life course, influenced by both residential mobility and neighborhood change, with potential implications for estimating the impact of neighborhoods on health. Commercial databases offer fine-grained longitudinal residential address data that can enrich life-course spatial epidemiology research, and validated methods for reconstructing residential histories from these databases are needed. Our study draws on unique data from a geographically diverse, population-based representative sample of adult Wisconsin residents and the LexisNexis (New York, New York) Accurint, a commercial personal profile database, to develop a systematic and reliable methodology for constructing individual residential histories. Our analysis demonstrated that creating residential histories across diverse geographical contexts is feasible, and it highlights differences in the information obtained from available residential histories by age, education, race/ethnicity, and rural/urban/suburban residency. Researchers should consider potential address data availability and information biases favoring socioeconomically advantaged individuals and their implications for studying health inequalities. Despite these limitations, LexisNexis data can generate varied residential exposure metrics and be linked to contextual data to enrich research into the contextual determinants of health at varied geographic scales.
Modeling the structure of the transmembrane domain of T1R3, a subunit of the sweet taste receptor, with neohesperidin dihydrochalcone using molecular dynamics simulation
Authors: Nakagita Tomoya , Matsuya Takumi , Narukawa Masataka , Kobayashi Takuya , Hirokawa Takatsugu , Misaka Takumi
Published: September 2023

Neohesperidin dihydrochalcone (NHDC) is a sweetener, which interacts with the transmembrane domain (TMD) of the T1R3 subunit of the human sweet taste receptor. Although NHDC and a sweet taste inhibitor lactisole share similar structural motifs, they have opposite effects on the receptor. This study involved the creation of an NHDC-docked model of T1R3 TMD through mutational analyses followed by in silico simulations. When certain NHDC derivatives were docked to the model, His7345.44 was demonstrated to play a crucial role in activating T1R3 TMD. The NHDC-docked model was then compared with a lactisole-docked inactive form, several residues were characterized as important for the recognition of NHDC; however, most of them were distinct from those of lactisole. Residues such as His6413.33 and Gln7947.38 were found to be oriented differently. This study provides useful information that will facilitate the design of sweeteners and inhibitors that interact with T1R3 TMD.
Cell electrospinning and its application in wound healing: principles, techniques and prospects
Authors: Hu Zonghao , Qin Zishun , Qu Yue , Wang Feng , Huang Benheng , Chen Gaigai , Liu Xiaoyuan , Yin Lihua
Published: September 2023

Currently, clinical strategies for the treatment of wounds are limited, especially in terms of achieving rapid wound healing. In recent years, based on the technique of electrospinning (ES), cell electrospinning (C-ES) has been developed to better repair related tissues or organs (such as skin, fat and muscle) by encapsulating living cells in a microfiber or nanofiber environment and constructing 3D living fiber scaffolds. Therefore, C-ES has promising prospects for promoting wound healing. In this article, C-ES technology and its advantages, the differences between C-ES and traditional ES, the parameters suitable for maintaining cytoactivity, and material selection and design issues are summarized. In addition, we review the application of C-ES in the fields of biomaterials and cells. Finally, the limitations and improved methods of C-ES are discussed. In conclusion, the potential advantages, limitations and prospects of C-ES application in wound healing are presented.
Microglia complement signaling promotes neuronal elimination and normal brain functional connectivity
Authors: Deivasigamani Senthilkumar , Miteva Mariya T , Natale Silvia , Gutierrez-Barragan Daniel , Basilico Bernadette , Di Angelantonio Silvia , Weinhard Laetitia , Molotkov Dmitry , Deb Sukrita , Pape Constantin , Bolasco Giulia , Galbusera Alberto , Asari Hiroki , Gozzi Alessandro , Ragozzino Davide , Gross Cornelius T
Published: September 2023

Complement signaling is thought to serve as an opsonization signal to promote the phagocytosis of synapses by microglia. However, while its role in synaptic remodeling has been demonstrated in the retino-thalamic system, it remains unclear whether complement signaling mediates synaptic pruning in the brain more generally. Here we found that mice lacking the Complement receptor 3, the major microglia complement receptor, failed to show a deficit in either synaptic pruning or axon elimination in the developing mouse cortex. Instead, mice lacking Complement receptor 3 exhibited a deficit in the perinatal elimination of neurons in the cortex, a deficit that is associated with increased cortical thickness and enhanced functional connectivity in these regions in adulthood. These data demonstrate a role for complement in promoting neuronal elimination in the developing cortex.
Rifampin Based Therapy for Patients With Staphylococcus aureus Native Vertebral Osteomyelitis: A Systematic Review and Meta-analysis
Authors: El Zein Said , Berbari Elie F , Passerini Matteo , Petri Francesco , Maamari Julian , Murad M Hassan , Sendi Parham , Tande Aaron J
Published: September 2023

Background

Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO.

Methods

We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI).

Results

Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, −14%; 95% CI, −19% to −8%; P < .001; I  2 = 0%; relative risk, 0.58; 95% CI, .37–.92, P = .02, I  2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low.

Conclusions

Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.
6. Defences to Negligence
Authors: Nolan Donal , Oliphant Ken
Published: September 2023

This chapter examines the following defences to a claim in negligence: volenti non fit injuria; contributory negligence; exclusion of liability; and illegality. The defence of volenti non fit injuria reflects the common sense notion that ‘[o]ne who has invited or assented to an act being done towards him cannot, when he suffers from it, complain of it as a wrong’. Contributory negligence is a partial defence that operates not to defeat the claimant’s claim entirely but rather to reduce the amount of damages the defendant must pay. A defendant may seek to exclude all potential liability to another person in advance of exposing himself to the risk of a possible claim. The defence of illegality denies recovery to certain claimants on the grounds that their claim is tainted by their own illegal conduct.
8. Negligence: Duty of Care—Economic Loss
Authors: Nolan Donal , Oliphant Ken
Published: September 2023

This chapter examines liability for economic loss in negligence, and in particular the limitations that apply to claims for such loss at the duty of care stage. The chapter begins with a discussion of the basic exclusionary rule in respect of pure economic loss, including the justifications that have been given for it. This is followed by a discussion of defective product economic loss; the Hedley Byrne exception; and economic loss recovery beyond Hedley Byrne (including White v Jones). The final section of the chapter first considers an economic analysis of the liability rules governing negligent misrepresentation, and then looks at rights-based and policy-based approaches to the law in this area.
14. Vicarious Liability
Authors: Nolan Donal , Oliphant Ken
Published: September 2023

The law of vicarious liability traditionally operates so as to impose liability on an employer for the tort of an employee, but several conditions must be satisfied. This chapter discusses the development of and justification for vicarious liability; the relationships that trigger vicarious liability, including the employment relationship and relationships ‘akin to employment’; and the requirement that the tort be committed in the course of employment for vicarious liability to arise. The chapter also considers the primary liability of an employer for the conduct of an employee or independent contractor, arising out of breach of a non-delegable duty of care.
16. Death and Damages
Authors: Nolan Donal , Oliphant Ken
Published: September 2023

This chapter first considers the effect of the death of one of the parties on an existing cause of action in tort. It then addresses the circumstances in which the wrongful death of another person gives rise to a new cause of action in those who have suffered loss as a result of the death, comparing the erstwhile exclusionary approach at common law with the nineteenth-century introduction of a new statutory action. The focus of the final part of the chapter is on the way in which damages are assessed under the modern version of that legislation, the Fatal Accidents Act 1976, with separate treatment of damages for loss of dependency and damages for bereavement.
Effects of social capital on healthcare utilization among older adults in Indonesia
Authors: Ekadinata Nopryan , Hsu Hui-Chuan , Chen Ya-Mei , Chuang Kun-Yang
Published: September 2023

Social capital potentially affects older adults’ access to healthcare services. However, the effects of social capital on the use of various types of healthcare services using longitudinal data have yet to be explored. This study aimed to examine the effects of structural and cognitive social capital on different types of healthcare utilization by older adults in Indonesia. Data were from the Indonesian Family Life Survey (waves 4 and 5) in 2007 and 2014. The sample consisted of participants aged 60 years and older who completed both waves (n = 1374). Healthcare utilization by older adults assessed health posts (posyandu), health checkups, outpatient care and hospital admissions. Social capital consisted of neighborhood trust and community participation. Generalized estimating equation models were used for the analysis. Older adults with high community participation had a higher likelihood of using preventive care in posyandu (OR = 5.848, 95% CI = 2.585–13.232) and health checkup visits (OR = 1.621, 95% CI = 1.116–2.356). Meanwhile, neighborhood trust was related to a higher probability of hospital admissions (OR = 1.255, 95% CI = 1.046–1.505). Social capital significantly affects older adults’ preventive and treatment healthcare utilization. Maximizing the availability of social participation and removing barriers to access to preventive and medical care in an age-friendly environment are suggested.
Cardiolipin deficiency leads to the destabilization of mitochondrial magnesium channel MRS2 in Barth syndrome
Authors: Joshi Alaumy , Gohil Vishal M
Published: September 2023

Barth syndrome (BTHS) is a debilitating X-linked cardio-skeletal myopathy caused by loss-of-function mutations in TAFAZZIN, a cardiolipin (CL)-remodeling enzyme required for the maintenance of normal levels of CL species in mitochondrial membranes. At present, how perturbations in CL abundance and composition lead to many debilitating clinical presentations in BTHS patients have not been fully elucidated. Inspired by our recent findings that CL is essential for optimal mitochondrial calcium uptake, we measured the levels of other biologically important metal ions in BTHS mitochondria and found that in addition to calcium, magnesium levels are significantly reduced. Consistent with this observation, we report a decreased abundance of the mitochondrial magnesium influx channel MRS2 in multiple models of BTHS including yeast, murine myoblast, and BTHS patient cells and cardiac tissue. Mechanistically, we attribute reduced steady-state levels of MRS2 to its increased turnover in CL-deficient BTHS models. By expressing Mrs2 in well-characterized yeast mutants of the phospholipid biosynthetic pathways, we demonstrate a specific requirement of CL for Mrs2 abundance and assembly. Finally, we provide in vitro evidence for the direct binding of CL with human MRS2. Together, our study has identified a critical requirement of CL for MRS2 stability and suggests perturbation of mitochondrial magnesium homeostasis as a novel contributing factor to BTHS pathology.
Sex Differences in Plasma, Adipose Tissue, and Central Accumulation of Cannabinoids, and Behavioral Effects of Oral Cannabis Consumption in Male and Female C57BL/6 Mice
Authors: Sallam Nada A , Peterson Colleen S , Baglot Samantha L , Kohro Yuta , Trang Tuan , Hill Matthew N , Borgland Stephanie L
Published: September 2023

Background

Cannabis edibles are an increasingly popular form of cannabis consumption. Oral consumption of cannabis has distinct physiological and behavioral effects compared with injection or inhalation. An animal model is needed to understand the pharmacokinetics and physiological effects of oral cannabis consumption in rodents as a model for human cannabis edible use.

Methods

Adult male and female C57BL/6 mice received a single dose of commercially available cannabis oil (5 mg/kg Δ⁹-tetrahydrocannabinol [THC]) by oral gavage. At 0.5, 1, 2, 3, and 6 hours post exposure, plasma, hippocampus, and adipose tissue were collected for THC, 11-OH-THC, and THC-COOH measures.

Results

We report delayed time to peak THC and 11-OH-THC concentrations in plasma, brain, and adipose tissue, which is consistent with human pharmacokinetics studies. We also found sex differences in the cannabis tetrad: (1) female mice had a delayed hypothermic effect 6 hours post consumption, which was not present in males; (2) females had stronger catalepsy than males; (3) males were less mobile following cannabis exposure, whereas female mice showed no difference in locomotion but an anxiogenic effect at 3 hours post exposure; and (4) male mice displayed a longer-lasting antinociceptive effect of oral cannabis.

Conclusions

Oral cannabis consumption is a translationally relevant form of administration that produces similar physiological effects as injection or vaping administration and thus should be considered as a viable approach for examining the physiological effects of cannabis moving forward. Furthermore, given the strong sex differences in metabolism of oral cannabis, these factors should be carefully considered when designing animal studies on the effects of cannabis.
New Directions in the Study of Populism in International Relations
Authors: Chryssogelos Angelos , Jenne Erin K , LaRoche Christopher David , Verbeek Bertjan , Zaslove Andrej , Destradi Sandra , Cadier David , Coticchia Fabrizio , Donelli Federico , Lequesne Christian
Published: September 2023

In recent years, there has been a growing interest in the international dimensions of populism, by now a major political phenomenon around the world. This interest, however, has been confined largely to the state level, especially the influence of populism on foreign policy. In this Forum, we argue that it is important for analysis to move beyond the state level and view populism as a concept and phenomenon of international relations (IR) rather than simply a factor of foreign policy. The Forum discusses implications of the rise of populism for IR theory, the role of international systemic change in the emergence of populism in national arenas, and the ways that regime type, state structure and institutions, ideational content, and the political strategies of populists condition the impact of populism on world politics. In this way, the Forum identifies specific directions for the study of populism in IR that scholars can follow in the future.
Human papillomavirus vaccination and anal high-grade precancerous lesions and cancer—a real-world effectiveness study
Authors: Baandrup Louise , Maltesen Thomas , Dehlendorff Christian , Kjaer Susanne K
Published: September 2023

Background

Human papillomavirus (HPV) vaccination has shown high efficacy against anal HPV infection and lesions in clinical trials, and the HPV prevalence and type distribution in anal precancers and cancer predict a high preventable potential for HPV vaccination. However, the real-world effectiveness of HPV vaccination against anal high-grade lesions and cancer is yet to be shown.

Methods

We investigated HPV vaccine effectiveness against anal high-grade squamous intraepithelial lesion (HSIL) or worse in a nationwide cohort including all Danish women aged 17-32 years during October 2006 to December 2021 (n = 968 881). HPV vaccinations and first occurrence of anal HSIL or worse were retrieved from nationwide registries. Women were considered vaccinated after first dose and classified by age at vaccination. Using Cox regression, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for anal HSIL or worse according to vaccination status.

Results

During follow-up, the number of incident histological anal HSIL or worse cases was 37 in unvaccinated women, and less than 5 and 26 in women vaccinated at ages younger than 17 years and 17-32 years, respectively. The overall number of cancers was less than 5. Compared with unvaccinated women, the risk of histological anal HSIL or worse was reduced for women vaccinated at age younger than 17 years (HR = 0.30, 95% CI = 0.10 to 0.87). For women vaccinated at age 17-32 years, the hazard rate of anal HSIL or worse was 1.21 (95% CI = 0.73 to 2.03).

Conclusion

This is the first study to demonstrate that HPV vaccination at a younger age is associated with substantially reduced risk of anal HSIL or worse in the general population.
Reconstructing the Antarctic ice-sheet shape at the Last Glacial Maximum using ice-core data
Authors: Turner Fiona E , Buck Caitlin E , Jones Julie M , Sime Louise C , Vallet Irene Malmierca , Wilkinson Richard D
Published: September 2023

The Antarctic ice sheet (AIS) is the Earth’s largest store of frozen water; understanding how it changed in the past allows us to improve projections of how it, and sea levels, may change. Here, we use previous AIS reconstructions, water isotope ratios from ice cores, and simulator predictions of the relationship between the ice-sheet shape and isotope ratios to create a model of the AIS at the Last Glacial Maximum. We develop a prior distribution that captures expert opinion about the AIS, generate a designed ensemble of potential shapes, run these through the climate model HadCM3, and train a Gaussian process emulator of the link between ice-sheet shape and isotope ratios. To make the analysis computationally tractable, we develop a preferential principal component method that allows us to reduce the dimension of the problem in a way that accounts for the differing importance we place in reconstructions, allowing us to create a basis that reflects prior uncertainty. We use Markov chain Monte Carlo to sample from the posterior distribution, finding shapes for which HadCM3 predicts isotope ratios closely matching observations from ice cores. The posterior distribution allows us to quantify the uncertainty in the reconstructed shape, a feature missing in other analyses.
Diagnosis of mucormycosis using a simple duplex PCR assay: Analysis of 160 clinical samples from COVID-19 patients
Authors: Aboutalebian Shima , Erami Mahzad , Ahsaniarani Amir Hossein , Momen-Heravi Mansooreh , Sharif Alireza , Hadipour Mahboubeh , Mirhendi Hossein
Published: September 2023

Early diagnosis of mucormycosis, a severe and potentially fatal complication in immunocompromised and COVID-19 patients, is crucial for initiating timely antifungal therapy and reducing infection mortality. In this study, the diagnostic performance of a duplex polymerase chain reaction (PCR) assay was evaluated to detect Mucorales-specific and Rhizopus oryzae-specific targets in 160 clinical samples collected from 112 COVID-19 patients suspected of invasive fungal rhinosinusitis (IFRS). During potassium hydroxide (KOH) direct microscopy, non-septate hyphae were observed in 73 out of 160 samples (45.63%); however, using duplex PCR, 82 out of 160 specimens (51.25%) tested positive. Among the positive PCR samples, 67 (81.71%) exhibited a double band (both 175 and 450 base pairs [bp]) indicating the presence of R. oryzae, and 15 (18.29%) showed only a single band (175 bp), suggesting the presence of non-R. oryzae Mucorales. DNAs from 10 microscopically negative samples and 4 samples with septate hyphae in microscopy were successfully amplified in PCR. Considering Calcofluor white fluorescence microscopy as the gold standard for laboratory diagnosis of mucormycosis, the duplex PCR assay utilized in this study exhibited a sensitivity of 93.88%, a specificity of 100%, a negative predictive value of 91.18%, and a positive predictive value of 100% for detecting mucormycosis in IFRS specimens. The duplex PCR assay demonstrated higher sensitivity compared to direct examination with KOH (82 vs. 73) and culture (82 vs. 41), enabling rapid detection/identification of Mucorales even in samples with negative culture or in biopsies with only a few hyphal elements.
Selection of Compton-thick AGN from a hard photometric sample using XMM–Newton observations
Authors: Mostafa Reham , Guainazzi Matteo , Ibrahim Alaa
Published: September 2023

We present a selection technique to detect Compton-thick (CT) active galactic nuclei (AGNs) in the 3XMM/SDSS-DR7 cross-correlation. A subsample of 3481 X-ray sources that are detected in the hard band (2–8 keV) and have photometric redshifts constitute our parent sample. We first applied an automated spectral-fitting procedure to select highly absorbed sources (NH > 1023 cm−2). We found 184 highly absorbed candidates. Then, we performed the Bayesian Monte Carlo Markov chains (MCMCs) selection technique to find CT AGNs. We also tested the MCMC selection technique by applying Monte Carlo simulations. We found that the method is accurate at 90 per cent independently of the nature of the underlying source. Our sample contains 52 bona fide CT AGNs. The CT AGNs were selected to have a range >0.75 of probability of being CT when either fitting with the two models Torus and MYTorus. About 75 per cent of CT AGNs in our sample had probabilities >90 per cent. From the spectral analysis, we significantly found an anticorrelation between the equivalent width of the neutral Fe K α line and the X-ray luminosity at 2–10 keV, the so-called X-ray Baldwin effect.
Contributions of histone tail clipping and acetylation in nucleosome transcription by RNA polymerase II
Authors: Oishi Takumi , Hatazawa Suguru , Kujirai Tomoya , Kato Junko , Kobayashi Yuki , Ogasawara Mitsuo , Akatsu Munetaka , Ehara Haruhiko , Sekine Shun-ichi , Hayashi Gosuke , Takizawa Yoshimasa , Kurumizaka Hitoshi
Published: September 2023

The N-terminal tails of histones protrude from the nucleosome core and are target sites for histone modifications, such as acetylation and methylation. Histone acetylation is considered to enhance transcription in chromatin. However, the contribution of the histone N-terminal tail to the nucleosome transcription by RNA polymerase II (RNAPII) has not been clarified. In the present study, we reconstituted nucleosomes lacking the N-terminal tail of each histone, H2A, H2B, H3 or H4, and performed RNAPII transcription assays. We found that the N-terminal tail of H3, but not H2A, H2B and H4, functions in RNAPII pausing at the SHL(-5) position of the nucleosome. Consistently, the RNAPII transcription assay also revealed that the nucleosome containing N-terminally acetylated H3 drastically alleviates RNAPII pausing at the SHL(-5) position. In addition, the H3 acetylated nucleosome produced increased amounts of the run-off transcript. These results provide important evidence that the H3 N-terminal tail plays a role in RNAPII pausing at the SHL(-5) position of the nucleosome, and its acetylation directly alleviates this nucleosome barrier.
Golden Standard: a complete standard, portable, and interoperative MoClo tool for model and non-model proteobacteria
Authors: Blázquez Blas , León David San , Torres-Bacete Jesús , Gómez-Luengo Álvaro , Kniewel Ryan , Martínez Igor , Sordon Sandra , Wilczak Aleksandra , Salgado Sergio , Huszcza Ewa , Popłoński Jarosław , Prieto Auxiliadora , Nogales Juan
Published: September 2023

Modular cloning has become a benchmark technology in synthetic biology. However, a notable disparity exists between its remarkable development and the need for standardization to facilitate seamless interoperability among systems. The field is thus impeded by an overwhelming proliferation of organism-specific systems that frequently lack compatibility. To overcome these issues, we present Golden Standard (GS), a Type IIS assembly method underpinned by the Standard European Vector Architecture. GS unlocks modular cloning applications for most bacteria, and delivers combinatorial multi-part assembly to create genetic circuits of up to twenty transcription units (TUs). Reliance on MoClo syntax renders GS fully compatible with many existing tools and it sets the path towards efficient reusability of available part libraries and assembled TUs. GS was validated in terms of DNA assembly, portability, interoperability and phenotype engineering in α-, β-, γ- and δ-proteobacteria. Furthermore, we provide a computational pipeline for parts characterization that was used to assess the performance of GS parts. To promote community-driven development of GS, we provide a dedicated web-portal including a repository of parts, vectors, and Wizard and Setup tools that guide users in designing constructs. Overall, GS establishes an open, standardized framework propelling the progress of synthetic biology as a whole.
DO GENOMIC ALTERATIONS INflUENCE THE DEVELOPMENT OF BRAIN METASTASES IN ADVANCED AND METASTATIC NON-SMALL CELL LUNG CANCER? A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Gillespie Conor , Mustafa Mohammad , Richardson George , Alam Ali , Lee Keng Siang , Hughes David , Escriu Carles , Zakaria Rasheed
Published: September 2023

AIMS

Establish prevalence at diagnosis, and incidence of BM in patients with advanced and metastatic non-small cell lung cancer (NSCLC), stratified by genomic alterations.

METHOD

A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO ID CRD42022315915). Three databases were searched (Search date 30th April 2022). Prevalence at diagnosis, and per-patient year incidence of brain metastases were obtained, including patients with EGFR, ALK, KRAS, ROS1, RET, and other genomic alterations. Pooled incidence rates were calculated using random effects models.

RESULTS

Of 960 articles identified, 65 were included (24,784 patients). The combined BM prevalence at diagnosis was 28.6% (45 studies, 95% Confidence Interval [CI] 26.1-31.0). Median follow-up was 24 months (Interquartile range [IQR] 16-36 months). The combined incidence of BM development was 10.8% per year (40 studies, 95% CI 9.2- 12.6). The per-year incidence of new BM was 15.6%/year in the EGFR +ve group (16 studies, 95% CI 11.4-21.2), 17.0% in the ALK+ve group (7 studies, 95% CI 11.3-25.8), 9.8% in the KRAS +ve group (4 studies, 95% CI 5.5-17.5), 12.5% in the ROS1 +ve group (3 studies, 95% CI 5.7-27.6), and 11.8% in the RET +ve group (2 studies, 95% CI 8.0-17.5). Combined overall prevalence was 55.0% (21 studies, IQR 44.2-67.8).

CONCLUSIONS

This systematic review indicates a high rate of brain metastases in NSCLC and is the first and only study to describe incidence, stratified by genomic alterations. This will have a major clinical impact by stratifying brain imaging at staging and follow-up by patient subgroup, particularly in ALK and EGFR mutations.
SYSTEMATIC IDENTIfiCATION OF CONTEXT-DEPENDENT GENE-ESSENTIALITY IN GLIOBLASTOMA: THE GBM-CODE PLATFORM
Authors: Foster Mitchell , Ewing Ailith , Frame Margaret , Brennan Paul , Khamseh Ava , Beentjes Sjoerd , Carragher Neil , Semple Colin
Published: September 2023

AIMS

Glioblastoma (GBM) is a heterogeneous and aggressive brain tumour that is invariably fatal despite maximal treatment. GBM-relevant ‘biomarkers’ (such as known driver-mutations or cell-states) could be used to stratify patients for treatments. However, pairing biomarkers with appropriate therapeutic ‘targets’ is challenging. If a gene is more essential in GBM cells which contain such a biomarker, inhibiting the gene product may be therapeutically useful in GBM tumours where that biomarker is present.

METHOD

We describe a novel computational tool which distils new translational insights from existing disparate large- scale biological data (genomics, transcriptomics and functional genomics data from 60 distinct patient-derived, IDH-wildtype, adult GBM cell lines) using Targeted Learning (a subfield of mathematics and causal machine learning) to systematically identify context-dependent gene essentiality in Glioblastoma (GBM-CoDE).

RESULTS

We derived multiple target-biomarker pair hypotheses, two of which (WWTR1 is more essential in EGFR- mutated/amplified GBM, and VRK1 is more essential in VRK2-methylated GBM) have recently been published by external groups, implying that our additional novel findings may be valid. We developed an interactive plat- form to make our findings accessible to other researchers to prioritise pairs for experimental validation and subsequent translation.

CONCLUSIONS

GBM-CoDE represents a potent new approach to solving the problem of developing patient-tailored therapeutics in GBM, made possible with recent innovations in computational biology. While the majority of these target- biomarker hypotheses have yet to be experimentally validated, our results may in time accelerate effective translation to biomarker stratified clinical trials in GBM. Our method is translatable to other cancers of unmet need.
END OF LIFE CARE IN BRAIN TUMOUR PATIENTS: DEMOGRAPHICS AND PREFERENCES
Authors: Mauricaite Radvile , Calvez Kerlann Le , Droney Joanne , Williams Matthew
Published: September 2023

AIMS

We used a regional NHS Electronic Palliative Care Coordination System (Coordinate My Care) to understand patient preferences and priorities for care at end-of-life. We present data on patient demographics and preferences and factors influencing the location of death in a primary brain tumour patient cohort.

METHOD

We identified all primary brain tumour patients from NW and SW London on the system. We examined patient demographics and compared the recorded preferred place of death (PPD) with the actual place and explored how patient demographics differ according to this.

RESULTS

Our dataset contains 1437 patients. 55% were male and 53% were 65 or older. 1222 (85%) were deceased. Of patients that had a recorded preference (N=987), 30 (3.0%) had hospital recorded as one of their two PPDs. Of those with a recorded place of death (N=864), 10.5% died in hospital. 24.8% had an unknown actual or PPD. Of those with a recorded preferred and actual place of death , 83.6% died in PPD. Patients who died at their preferred location had lower overall survival and were more likely to have stayed in a care home. A higher percentage of men compared to females died in a location other than their PPD.

CONCLUSIONS

Here we present preliminary analysis of patient provided data and their preferences for end-of-life care. We will triangulate these data end-of-life care data from Gliocova project, where we have data on over 50,000 brain tumour patients, to get a more in depth understanding of the patient care in the last months of life.
LOW-GRADE GLIOMAS IN OLDER PATIENTS: A MATCHED PROPENSITY-SCORING ANALYSIS TO DETERMINE SEIZURE OUTCOMES AND PROGNOSIS
Authors: Lee Jing Xian , Waqar Mueez , Younis Michael , Maye Helen , Bailey Matthew , D’urso Pietro , Coope David , Youshani Amir Saam , Karabatsou Konstantina
Published: September 2023

AIMS

Low-grade gliomas (LGG) are associated with significant morbidity and age is assumed to be a negative prognostic factor. The aim of this study was to compare outcomes between older patients with LGGs and a matched cohort of younger patients.

METHOD

Retrospective review of WHO grade II LGGs from 2009-2022. Propensity-score matching (1:3 matching) was used to compare older (≥65 years old) and matched younger controls (<65 years old). The two groups were matched by age, gender, presenting seizures, Karnofsky performance status, location, extent of resection, use of awake neurosurgical monitoring, histology subtype and post-operative chemoradiotherapy. Survival analysis was performed using Kaplan-Meier survival curves and log-rank test.

RESULTS

40 patients were included - 10 older and 30 young. The median age was 70.0 and 48.5 years, respectively, with no differences in other demographic variables. Following resection, the older group had a shorter seizure-free period (median 2.5 vs. 10.9 months) and worse 1-year seizure-free rates (25.0% vs. 50.0%). Other outcomes were also worse in the older group including a shorter overall survival (median 95.0 vs. 117.0 months) and shorter progression-free survival (median 24.0 vs. 61.0 months).

CONCLUSIONS

In this novel study, we present the first matched analysis to evaluate outcomes in older patients with LGGs. We report worse seizure outcomes, overall survival and progression-free survival in these patients. Larger longitudinal multicentre studies will more accurately assess post-operative seizure-control and prognostic outcomes in between these groups.
A SINGLE CENTRE 10-YEAR EXPERIENCE WITH GAMMA KNIFE STEREOTACTIC RADIOSURGERY FOR CEREBRAL METASTASES
Authors: Crispi Vassili , Reveendran Dharsshini , Hatfield Paul , Mathew Ryan
Published: September 2023

AIMS

An estimated 20-40% of patients with metastatic cancer will have brain metastases, whose management depends on multiple factors. Stereotactic radiosurgery (SRS) is increasingly preferred to whole brain radio- therapy (WBRT), since it delivers a precise, high-dose of radiation to individual metastases.

This study evaluated the 10-year experience of SRS at the Leeds Gamma Knife Centre.

METHOD

This is a retrospective, observational study of patients undergoing SRS between 2010 and 2020. Data on primary tumour, Karnofsky Performance Status (KPS), previous treatment for brain metastases, intracranial disease burden, oral steroid therapy, and toxicity were recorded. Follow-up was undertaken for a minimum of 6 months with regular MRI brain.

RESULTS

3,940 intracranial metastases in 1,113 patients (478 male) were treated with SRS. Lung (48.2%) and breast (15%) were the most common primary tumours. Median survival was 10 months. Using multivariate analysis, primary diagnosis (p<0.001), KPS (p<0.001), number of lesions (p=0.005) and total tumour volume (p=0.012) were the most statistically significant predictors of survival.

At follow-up, 375 (33.7%) patients had new brain metastases. Median time to new metastases was 6 months, and 195 (17.5%) patients underwent further SRS with a median time to repeat SRS of 7 months.

Side effects following SRS were usually very mild, primarily including short-term fatigue (28.8%). Steroid dose also dropped significantly after SRS(p<0.001).

CONCLUSIONS

This 10-year analysis of SRS in brain metastases demonstrated a statistically significant association of survival with pre-treatment predictors, including primary diagnosis, KPS, intracranial disease burden. SRS provides minimal side effects with an associated significant decrease in steroid use following treatment.