bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Experiences of Caregivers of Spouses With Dementia During Caregiver Health Care Emergencies
Authors: Daddato Andrea E , Gleason Kathy S , Dollar Blythe A , McPhail Tobie E , Kraus Courtney R , Boxer Rebecca S
Published: January 2024

Background and Objectives

Caregivers of persons with dementia are frequently spouses. Caregiver hospitalization causes disruption to caregiving. The goal of this research was to understand the preparedness and stress trajectory of peri-caregiver hospitalization.

Research Design and Methods

Mixed methods were used. Caregivers of spouses with dementia (n = 1,000) were surveyed to determine their perceived preparedness for their own hospitalization. Journey mapping interviews (n = 18) were used to map caregivers’ experiences during 5 phases: (a) their spouse with dementia (SWD)’s dementia diagnosis; (b) their SWD’s dementia progression; (c) their own health event; (d) their own hospitalization; and (e) their own return home from the hospital.

Results

Among the 452 (45%) eligible caregiver survey respondents, 75 (17%) had experienced hospitalization in the previous 12 months and 51 (68%) hospitalizations were unexpected. Twenty-three (31%) of hospitalized caregivers indicated they did not have prior plans in place for the care of the SWD. When asked about an unexpected hospitalization in the future, 233 (52%) felt somewhat prepared and 133 (29%) felt not at all prepared. Journey mapping revealed 3 groups of caregivers: Group 1 (n = 7) rated their stress lower during their hospitalization, Group 2 (n = 7) rated their stress highest during their hospitalization, and Group 3 (n = 4) were at a sustained high-stress level.

Discussion and Implications

Many caregivers are not prepared for their own hospitalization. The stress trajectory through important phases of dementia caregiving and a caregiver’s own hospitalization is not universal. Meeting the needs of caregivers’ peri-hospitalization should be tailored to the individual caregiver.
Effect of message framing on support for a sugar-sweetened beverage tax in Australia: a cross-sectional survey analysis
Authors: Cullerton Katherine , Demeshko Anastassia , Waller Michael
Published: January 2024

Sugar-sweetened beverage (SSB) taxes are present in many countries with evidence that they are effective in decreasing purchases of SSBs. However, in Australia where SSB consumption per capita is high, and calls for an SSB tax are frequent, there is no SSB tax and policymakers have stated their lack of support for such a tax. We examined whether political party voting preference and sociodemographic factors affect individuals’ support for an SSB tax, and whether message framing affects this support. A nationally representative sample of 1519 Australian adults was recruited for an online experimental survey. Three persuasive frames and one control frame were randomly provided to participants and measures of agreement towards an SSB tax were assessed. Sociodemographic factors and political party preference were also captured. Message framing had minimal effect on the level of support for the tax. However, participants who received the ‘supportive of food and drink companies frame’ showed the highest positive feelings towards the tax, and participants in rural areas had higher levels of support for an SSB tax when receiving the ‘protecting teenagers’ frame. Participants who voted for conservative (right-leaning) parties and for Labour (a centre-left party) had similar levels of support towards the tax, which was considerably lower than Greens voters. Undecided voters had the lowest levels of support for the tax, and the frames had limited impact on them. These findings highlight the potential role of message framing in shaping public support for an SSB tax in Australia, particularly in the context of voting preference and sociodemographic factors.
Flowering genes identification, network analysis, and database construction for 837 plants
Authors: Wu Tong , Liu Zhuo , Yu Tong , Zhou Rong , Yang Qihang , Cao Rui , Nie Fulei , Ma Xiao , Bai Yun , Song Xiaoming
Published: January 2024

Flowering is one of the most important biological phenomena in the plant kingdom, which not only has important ecological significance, but also has substantial horticultural ornamental value. In this study, we undertook an exhaustive review of the advancements in our understanding of plant flowering genes. We delved into the identification and conducted comparative analyses of flowering genes across virtually all sequenced angiosperm plant genomes. Furthermore, we established an extensive angiosperm flowering atlas, encompassing a staggering 183 720 genes across eight pathways, along with 10 155 ABCDE mode genes, which play a pivotal role in plant flowering regulation. Through the examination of expression patterns, we unveiled the specificities of these flowering genes. An interaction network between flowering genes of the ABCDE model and their corresponding upstream genes offered a blueprint for comprehending their regulatory mechanisms. Moreover, we predicted the miRNA and target genes linked to the flowering processes of each species. To culminate our efforts, we have built a user-friendly web interface, named the Plant Flowering-time Gene Database (PFGD), accessible at http://pfgd.bio2db.com/. We firmly believe that this database will serve as a cornerstone in the global research community, facilitating the in-depth exploration of flowering genes in the plant kingdom. In summation, this pioneering endeavor represents the first comprehensive collection and comparative analysis of flowering genes in plants, offering valuable resources for the study of plant flowering genetics.
How do kernel-based sensor fusion algorithms behave under high-dimensional noise?
Authors: Ding Xiucai , Wu Hau-Tieng
Published: January 2024

We study the behavior of two kernel based sensor fusion algorithms, nonparametric canonical correlation analysis (NCCA) and alternating diffusion (AD), under the nonnull setting that the clean datasets collected from two sensors are modeled by a common low-dimensional manifold embedded in a high-dimensional Euclidean space and the datasets are corrupted by high-dimensional noise. We establish the asymptotic limits and convergence rates for the eigenvalues of the associated kernel matrices assuming that the sample dimension and sample size are comparably large, where NCCA and AD are conducted using the Gaussian kernel. It turns out that both the asymptotic limits and convergence rates depend on the signal-to-noise ratio (SNR) of each sensor and selected bandwidths. On one hand, we show that if NCCA and AD are directly applied to the noisy point clouds without any sanity check, it may generate artificial information that misleads scientists’ interpretation. On the other hand, we prove that if the bandwidths are selected adequately, both NCCA and AD can be made robust to high-dimensional noise when the SNRs are relatively large.
Prevalence and Phenotypic Susceptibility to Doravirine of the HIV-1 Reverse Transcriptase V106I Polymorphism in B and Non-B Subtypes
Authors: Giammarino Federica , de Salazar Adolfo , Malet Isabelle , Viñuela Laura , Fuentes Ana , Saladini Francesco , Bartolini Niccolò , Charpentier Charlotte , Lambert-Niclot Sidonie , Sterrantino Gaetana , Colao Maria Grazia , Micheli Valeria , Bertoli Ada , Fabeni Lavinia , Teyssou Elisa , Delgado Rafael , Falces-Romero Iker , Aguilera Antonio , Gomes Perpetua , Paraskevis Dimitrios , Santoro Maria M , Ceccherini-Silberstein Francesca , Marcelin Anne-Genevieve , Moreno Cristina , Zazzi Maurizio , García Federico
Published: January 2024

Background

Limited data are available regarding the susceptibility of the reverse transcriptase V106 polymorphism to doravirine.

Methods

Doravirine susceptibility was measured in site-directed mutants (SDMs) containing V106I, V106A, V106M, and Y188L mutations in subtype B (NL4-3, HXB2) and CRF02_AG background and in recombinant viruses with RT harboring V106I alone derived from 50 people with HIV.

Results

HIV-1 B subtype was detected in 1523 of 2705 cases. Prevalence of V106I was 3.2% in B and 2.5% in non-B subtypes, and was higher in subtype F (8.1%) and D (14.3%). Fold-changes (FC) in susceptibility for SDMs were below doravirine biological cutoff (3.0) for V106I, but not for V106A, V106M, and Y188L. Clinically derived viruses tested included 22 B (median FC, 1.2; interquartile range [IQR], 0.9–1.6) and 28 non-B subtypes (median FC, 1.8; IQR, 0.9–3.0). Nine (18%) viruses showed FC values equal or higher than the doravirine biological FC cutoff.

Conclusions

The prevalence of the HIV-1 RT V106I polymorphism in MeditRes HIV consortium remains low, but significantly more prevalent in subtypes D and F. V106I minimally decreased the susceptibility to doravirine in SDMs and most clinical isolates. Reduced susceptibility seems to occur at increased frequency in subtype F1; however, the clinical impact remains to be investigated.

Clinical Trials Registration

NCT04894357.
Ecological niches and assembly dynamics of diverse microbial consortia in the gastrointestine of goat kids
Authors: Jiao Jinzhen , Wu Jian , Zhou Chuanshe , He Zhixiong , Tan Zhiliang , Wang Min
Published: January 2024

Goats are globally invaluable ruminants that balance food security and environmental impacts, and their commensal microbiome residing in the gastrointestinal tract (GIT) is associated with animal health and productivity. However, the reference genomes and functional repertoires of GIT microbes in goat kids have not been fully elucidated. Herein, we performed a comprehensive landscape survey of the GIT microbiome of goat kids using metagenomic sequencing and binning, spanning a dense sampling regime covering three gastrointestinal compartments spatially and five developmental ages temporally. We recovered 1002 high-quality metagenome-assembled genomes (termed the goat kid GIT microbial catalog [GKGMC]), 618 of which were novel. They encode more than 2.3 million nonredundant proteins, and represent a variety of carbohydrate-degrading enzymes and metabolic gene clusters. The GKGMC-enriched microbial taxa, particularly Sodaliphilus, expanded the microbial tree of life in goat kids. Using this GKGMC, we first deciphered the prevalence of fiber-degrading bacteria for carbohydrate decomposition in the rumen and colon, while the ileal microbiota specialized in the uptake and conversion of simple sugars. Moreover, GIT microorganisms were rapidly assembled after birth, and their carbohydrate metabolic adaptation occurred in three phases of progression. Finally, phytobiotics modified the metabolic cascades of the ileal microbiome, underpinned by the enrichment of Sharpea azabuensis and Olsenella spp. implicated in lactate formation and utilization. This GKGMC reference provides novel insights into the early-life microbial developmental dynamics in distinct compartments, and offers expanded resources for GIT microbiota-related research in goat kids.
Exploring the Impact of Matching E-Training Material to Arabic Dyslexia Type on Learners’ Reading Performance, Satisfaction and Behaviour
Authors: Al-Dawsari Hadeel Mohammed , Hendley Robert
Published: January 2024

Dyslexia is a reading difficulty that can be found everywhere, regardless of a person’s ethnicity or race. The manifestation of dyslexia depends on the structure and orthography of a language. There is a lack of research into Arabic dyslexia, particularly the benefits of adaptive learning in this area. The study presented in this paper aimed to understand the impact on learners’ reading performance, satisfaction and behaviour when matching e-training material with learner attributes. The focus is on learners with short vowel dyslexia. The study was undertaken with 22 female primary school children in Saudi Arabia, all of whom were native Arabic speakers. These children were divided into two groups: a matched group (which included learners with short vowel dyslexia) and a mismatched group (which included learners with vowel dyslexia). An e-training system ‘DysTypeTrain2’ was designed and developed to support the study. A mixed-methods approach was used to collect both quantitative and qualitative data. The quantitative data were collected from (i) pre- and post-test results to calculate the improvement in reading performance and (ii) learner satisfaction scores. The qualitative data were collected from observations of learners’ behaviour. It was found that the learners’ reading performance and satisfaction improved in both experimental conditions (short vowel dyslexia group and vowel dyslexia group), regardless of their Arabic dyslexia type, indicating that the system was effective and the learning process was improved. Further, the learners were happy and excited about the system.
Anti-biofilm and antivirulence activities of 1,2,6-tri-O-galloyl-β-d-glucose against Proteus penneri
Authors: Jiang Huan , Wang Zhennan , Jia Ai-Qun
Published: January 2024

Aims

The present study investigated the anti-virulence and anti-biofilm effects of 1,2,6-tri-O-galloyl-β-d-glucose (TGG), isolated from Camellia nitidissima Chi flowers, on Proteus penneri ALK 1200.

Methods and results

TGG was isolated from C. nitidissima Chi flowers using various chromatographic techniques. The milk plate assay, azocasein assay, and exopolysaccharides (EPS) inhibition assay revealed that TGG effectively inhibited the production of crucial virulence factors, including protease and EPS, in P. penneri ALK 1200. Furthermore, Fourier transform infrared spectroscopic analysis indicated that TGG interfered with the composition of P. penneri ALK 1200’s cellular component, potentially reducing the bacteria’s pathogenicity. In addition, crystal violet assay, scanning electron microscopy, and confocal laser scanning microscopy analysis indicated a significant reduction in biofilm formation following TGG treatment. The swimming and swarming assays also showed that TGG reduced the motility of P. penneri ALK 1200. Furthermore, the quantitative real-time PCR assay demonstrated that TGG down-regulated the expression of positive regulatory genes (hfq and flhD) responsible for motility and biofilm formation, while up-regulating the expression of the negative regulator of the quorum sensing system, bssS, in P. penneri ALK 1200.

Conclusions

TGG displayed potent anti-QS and anti-biofilm activity toward P. penneri ALK 1200.
Right to Privacy and Data Protection Concerns Raised by the Development and Usage of Face Recognition Technologies in the European Union
Authors: Kavoliūnaitė-Ragauskienė Eglė
Published: January 2024

The fast and fragmentedly regulated development of facial recognition technologies and related artificial intelligence poses various challenges to personal privacy, which leads to potential infringements of a wide range of related human rights. This article analyses the threats that the development and use of facial recognition technologies pose to privacy and personal data protection. It discusses the concept of privacy and the protection of personal data, including biometric data, at European Union level, and assesses the proposed new legal framework. It questions whether this is sufficient to protect privacy and ensure personal data protection in the context of the rapid development and increasing usage of facial recognition technologies in public and private sectors.
Piloting delivery of PfSPZ vaccines for malaria through a cryogenic vaccine cold chain to travel and military medicine clinics
Authors: James Eric R , Church L W Preston , Hoffman Stephen L , Richie Thomas L , Robertson Brian D , Hickey Patrick W , Schwartz David J , Logan Patrick T , Asare Theresa D , Jones Macie L , Bay Jeannie L , Roschel Austin K , Pfeiffer Jacqueline L , Acosta Rebecca W , Schiavi Ethan , Acosta Alberto M , Noble Mark , Henkel Thomas , Young Cebrina
Published: January 2024

Background

PfSPZ vaccines comprising Plasmodium falciparum (Pf) sporozoites (SPZ) have demonstrated > 90% protection against variant Pf malaria infections for at least 12 weeks; they are the only vaccines with the level of efficacy necessary to protect travellers. PfSPZ are eukaryotic cells stabilized by cryopreservation and distributed using a cryogenic (below −150 °C) cold chain. The Ebola vaccine and mRNA vaccines against SARS-CoV-2 pioneered uptake of vaccines requiring non-standard ultra-low temperature cold chains. The cryogenic cold chain using liquid nitrogen (LN2) vapour phase (LNVP) cryoshippers, is simpler, more efficient than −80, −20 or 2–8 °C cold chains, and does not use electricity. This study was conducted to evaluate implementation and integration of a cryogenically distributed vaccine at travel and military immunization clinics.

Methods

We conducted sequential 28-day studies evaluating vaccine shipping, storage, maintenance and accession at two US military and two civilian travel health/immunization clinics. In each clinic, personnel were trained in equipment use, procurement and handling of LN2, temperature monitoring and inventory record keeping by in-person or video instruction.

Results

Sites required 2–4 h/person for two persons to assimilate and develop the expertise to manage vaccine storage and LNVP operations. LN2 for recharging cryoshippers was delivered every 1–2 weeks. Vaccine ordering, receipt, storage and inventory control was conducted effectively. Simulated single dose vaccine cryovial retrieval and thawing were performed successfully in different travel clinic settings. Continuous temperature monitoring at each site was maintained with only one short excursion above −150 °C (−145 °C) through shipping, use and reverse logistics. Staff, during and at study conclusion, provided feedback that has been incorporated into our models for cold chain logistics.

Conclusions

These studies demonstrated that the training in delivery, storage, administration and integration of PfSPZ vaccines can be successfully managed in different immunization clinic settings for travellers and military personnel.
Topic modelling literary interviews from The Paris Review
Authors: Greene Derek , O'Sullivan James , O'Reilly Daragh
Published: January 2024

The interview has always proved to be a rich source for those hoping to better understand the figures behind a text, as well as any social contexts and writing practices which might have informed their aesthetic sentiments. Over the past two decades, research into the literary interview has made significant strides, both in terms of how this literary genre is conceptualized and how its emergence and development has been historically traced, the form remains somewhat neglected by literary and cultural theorists and scholars. There is also a remarkable absence of distant readings in this domain. With the rise of the digital humanities, particularly digital literary studies, one would expect more scholars to have used computer-assisted techniques to mine literary interviews, which are, in terms of dataset practicalities, somewhat ideal, semi-structured by nature, and typically available online. Such is the question to which this article attends, taking as its dataset seven decades’ worth of literary interviews from The Paris Review, and ‘topic modelling’ these documents to determine the key themes that dominate such a culturally significant set of materials while also exploring the value of topic modelling to socio-literary criticism.
LAMOST J040901.83+329355.6 – a new Galactic star with Wolf–Rayet characteristics in the transitional stage from post-asymptotic giant branch to central star of a planetary nebula
Authors: Maryeva Olga , Abdulkarimova Aynur , Karpov Sergey , Moiseev Alexei , Oparin Dmitry
Published: January 2024

The similarity in physical conditions in the winds of low-mass post-asymptotic giant branch stars and evolved massive stars leads to the appearance of an interesting phenomenon of spectral mimicry. Because of this, the discovery of every new star with a Wolf–Rayet (WR) spectrum requires a special study of its evolutionary status before it can be included in the list of Galactic WR stars. A couple of years ago, LAMOST J040901.83+323955.6 (hereafter J0409+3239) was selected as a WR star in the LAMOST spectroscopic data base by machine-learning methods. In this work, we investigate its evolutionary status. After analysing the spatial location of J0409+3239  in the Galaxy and its position in the colour–magnitude diagram, we conclude that J0409+3239  is instead a low-mass object displayng the WR phenomenon. Its luminosity is $L*=1000~\rm L_\odot$ and its effective temperature is Teff = 40 000 K. Using new and archival photometric data, we detected irregular variability on time-scales from hours to tens of days with an amplitude of up to ~0.2 mag. A comparison of the spectrum obtained in 2022 with that from 2014 also shows evidence of spectral variability. The absence of a clearly detected circumstellar nebula prevents the classification of J0409+3239  as [WR], namely as the central star of a planetary nebula (CSPN). However, the position of J0409+3239 on the Hertzsprung–Russell diagram suggests that this object  is a low-mass star caught in a rare transitional phase to CSPN. Estimation of the J0409+3239  mass based on evolutionary tracks shows that it is less than $0.9~\rm M_\odot$, and thus that the age of the Galaxy is barely sufficient for the star to have evolved to its current stage.
Neutral carbon in diffuse interstellar medium: abundance matching with H2 for damped Lyman alpha systems at high redshifts
Authors: Balashev S A , Kosenko D N
Published: January 2024

We present a study of C i/H2 relative abundance in the diffuse cold neutral medium (CNM). Using the chemical and thermal balance model, we calculate the dependence of C i/H2 on the main parameters of the medium: hydrogen number density, metallicity, strength of the UV field, and cosmic ray ionization rate (CRIR). We show that the observed relative C i and H2 column densities in damped Lyman alpha systems (DLAs) at high redshifts can be reproduced within our model assuming the typically expected conditions in the diffuse CNM. Using additional observed information on metallicity, H i column density, and excitation of C i fine-structure levels, as well as temperature, we estimated for a wide range metallicities in the CNM at high redshifts that CRIRs are in the range from ∼10−16 to a $\rm few \times 10^{-15}\, \rm s^{-1}$, hydrogen number densities are in the range ∼10−103 cm−3, and the UV field is in the range from 10−2 to a $\rm few \times 10^2$ of the Mathis field. We argue that because the observed quantities used in this work are quite homogeneous and much less affected by radiative transfer effects (in comparison with, for example, the dissociation of HD and UV pumping of H2 rotational levels), our estimates are quite robust against the assumption of the exact geometrical model of the cloud and local sources of the UV field.
Astroconformer: The prospects of analysing stellar light curves with transformer-based deep learning models
Authors: Pan Jia-Shu , Ting Yuan-Sen , Yu Jie
Published: January 2024

Stellar light curves contain valuable information about oscillations and granulation, offering insights into stars’ internal structures and evolutionary states. Traditional asteroseismic techniques, primarily focused on power spectral analysis, often overlook the crucial phase information in these light curves. Addressing this gap, recent machine learning applications, particularly those using Convolutional Neural Networks (CNNs), have made strides in inferring stellar properties from light curves. However, CNNs are limited by their localized feature extraction capabilities. In response, we introduce Astroconformer, a Transformer-based deep learning framework, specifically designed to capture long-range dependencies in stellar light curves. Our empirical analysis centres on estimating surface gravity (log g), using a data set derived from single-quarter Kepler light curves with log g values ranging from 0.2 to 4.4. Astroconformer demonstrates superior performance, achieving a root-mean-square-error (RMSE) of 0.017 dex at log g ≈ 3 in data-rich regimes and up to 0.1 dex in sparser areas. This performance surpasses both K-nearest neighbour models and advanced CNNs. Ablation studies highlight the influence of receptive field size on model effectiveness, with larger fields correlating to improved results. Astroconformer also excels in extracting νmax with high precision. It achieves less than 2 per cent relative median absolute error for 90-d red giant light curves. Notably, the error remains under 3 per cent for 30-d light curves, whose oscillations are undetectable by a conventional pipeline in 30 per cent cases. Furthermore, the attention mechanisms in Astroconformer align closely with the characteristics of stellar oscillations and granulation observed in light curves.
On using the counting method to constrain the anisotropy of kilonova radiation
Authors: Zhang Siqi , Deng Furen , Lu Youjun
Published: January 2024

A large number of binary neutron star (BNS) mergers are expected to be detected by gravitational wave (GW) detectors and the electromagnetic (EM) counterparts (e.g. kilonovae) of a fraction of these mergers may be detected in multibands by large area survey telescopes. For a given number of BNS mergers detected by their GW signals, the expected numbers of their EM counterparts that can be detected by a survey with given selection criteria depend on the kilonova properties, including the anisotropy. In this paper, we investigate whether the anisotropy of kilonova radiation and the kilonova model can be constrained statistically by the counting method, i.e. using the numbers of BNS mergers detected via GW and multiband EM signals. Adopting simple models for the BNS mergers, afterglows, and a simple two (blue and red)-component model for kilonovae, we generate mock samples for GW detected BNS mergers, their associated kilonovae, and afterglows detected in multibands. By assuming some criteria for searching the EM counterparts, we simulate the observations of these EM counterparts and obtain the EM observed samples in different bands. With the numbers of BNS mergers detected by GW detectors and EM survey telescopes in different bands, we show that the anisotropy of kilonova radiation and the kilonova model can be well constrained by using the Bayesian analysis. Our results suggest that the anisotropy of kilonova radiation may be demographically and globally constrained by simply using the detection numbers of BNS mergers by GW detectors and EM survey telescopes in multibands.
Stability of dusty rings in protoplanetary discs
Authors: Chan Kevin , Paardekooper Sijme-Jan
Published: January 2024

Dust rings in protoplanetary discs are often observed in thermal dust emission and could be favourable environments for planet formation. While dust rings readily form in gas pressure maxima, their long-term stability is key to both their observability and potential to assist in planet formation. We investigate the stability of the dust ring generated by interactions of a protoplanetary disc with a Neptune-sized planet and consider its possible long-term evolution using the FARGO3D Multifluid code. We look at the onset of the Rossby Wave Instability (RWI) and compare how the addition of dust in a disc can alter the stability of the gas phase. We find that with the addition of dust, the rings generated by planet–disc interactions are more prone to RWI and can cause the gas phase to become unstable. The instability is shown to occur more easily for higher Stokes number dust, as it accumulates into a more narrow ring which triggers the RWI, while the initial dust fraction plays a more minor role in the stability properties. We show that the dusty RWI generates vortices that collect dust in their cores, which could be sites for further planetesimal formation. We conclude that the addition of dust can cause a ring in a protoplanetary disc to become more prone to instability leading to a different long-term evolution compared to gas-only simulations of the RWI.
On the likely magnesium–iron silicate dusty tails of catastrophically evaporating rocky planets
Authors: Campos Estrada Beatriz , Owen James E , Jankovic Marija R , Wilson Anna , Helling Christiane
Published: January 2024

Catastrophically evaporating rocky planets provide a unique opportunity to study the composition of small planets. The surface composition of these planets can be constrained via modelling their comet-like tails of dust. In this work, we present a new self-consistent model of the dusty tails: we physically model the trajectory of the dust grains after they have left the gaseous outflow, including an on-the-fly calculation of the dust cloud’s optical depth. We model two catastrophically evaporating planets: KIC 1255 b and K2-22 b. For both planets, we find the dust is likely composed of magnesium–iron silicates (olivine and pyroxene), consistent with an Earth-like composition. We constrain the initial dust grain sizes to be ∼ 1.25–1.75 μm and the average (dusty) planetary mass-loss rate to be ∼ 3$\, M_{\oplus } \mathrm{Gyr^{-1}}$. Our model shows that the origin of the leading tail of dust of K2-22 b is likely a combination of the geometry of the outflow and a low radiation pressure force to stellar gravitational force ratio. We find the optical depth of the dust cloud to be a factor of a few in the vicinity of the planet. Our composition constraint supports the recently suggested idea that the dusty outflows of these planets go through a greenhouse effect–nuclear winter cycle, which gives origin to the observed transit depth time variability. Magnesium–iron silicates have the necessary visible-to-infrared opacity ratio to give origin to this cycle in the high mass-loss state.
Cosmology from weak lensing peaks and minima with Subaru Hyper Suprime-Cam Survey first-year data
Authors: Marques Gabriela A , Liu Jia , Shirasaki Masato , Thiele Leander , Grandón Daniela , Huffenberger Kevin M , Cheng Sihao , Harnois-Déraps Joachim , Osato Ken , Coulton William R
Published: January 2024

We present cosmological constraints derived from peak counts, minimum counts, and the angular power spectrum of the Subaru Hyper Suprime-Cam first-year (HSC Y1) weak lensing shear catalogue. Weak lensing peak and minimum counts contain non-Gaussian information and hence are complementary to the conventional two-point statistics in constraining cosmology. In this work, we forward-model the three summary statistics and their dependence on cosmology, using a suite of N-body simulations tailored to the HSC Y1 data. We investigate systematic and astrophysical effects including intrinsic alignments, baryon feedback, multiplicative bias, and photometric redshift uncertainties. We mitigate the impact of these systematics by applying cuts on angular scales, smoothing scales, signal-to-noise ratio bins, and tomographic redshift bins. By combining peaks, minima, and the power spectrum, assuming a flat-ΛCDM model, we obtain $S_{8} \equiv \sigma _8\sqrt{\Omega _m/0.3}= 0.810^{+0.022}_{-0.026}$, a 35 per cent tighter constraint than that obtained from the angular power spectrum alone. Our results are in agreement with other studies using HSC weak lensing shear data, as well as with Planck 2018 cosmology and recent CMB lensing constraints from the Atacama Cosmology Telescope and the South Pole Telescope.
Preclinical exploration of the DNA damage response pathway using the interactive neuroblastoma cell line explorer CLEAN
Authors: Gabre Jonatan L , Merseburger Peter , Claeys Arne , Siaw Joachim , Bekaert Sarah-Lee , Speleman Frank , Hallberg Bengt , Palmer Ruth H , Van den Eynden Jimmy
Published: January 2024

Neuroblastoma (NB) is the most common cancer in infancy with an urgent need for more efficient targeted therapies. The development of novel (combinatorial) treatment strategies relies on extensive explorations of signaling perturbations in neuroblastoma cell lines, using RNA-Seq or other high throughput technologies (e.g. phosphoproteomics). This typically requires dedicated bioinformatics support, which is not always available. Additionally, while data from published studies are highly valuable and raw data (e.g. fastq files) are nowadays released in public repositories, data processing is time-consuming and again difficult without bioinformatics support. To facilitate NB research, more user-friendly and immediately accessible platforms are needed to explore newly generated as well as existing high throughput data. To make this possible, we developed an interactive data centralization and visualization web application, called CLEAN (the Cell Line Explorer web Application of Neuroblastoma data; https://ccgg.ugent.be/shiny/clean/). By focusing on the regulation of the DNA damage response, a therapeutic target of major interest in neuroblastoma, we demonstrate how CLEAN can be used to gain novel mechanistic insights and identify putative drug targets in neuroblastoma.
TSCRE: a comprehensive database for tumor-specific cis-regulatory elements
Authors: Peng Guanjie , Liu Bingyuan , Zheng Mohan , Zhang Luowanyue , Li Huiqin , Liu Mengni , Liang Yuan , Chen Tianjian , Luo Xiaotong , Shi Xianping , Ren Jian , Zheng Yueyuan
Published: January 2024

Cis-regulatory elements (CREs) and super cis-regulatory elements (SCREs) are non-coding DNA regions which influence the transcription of nearby genes and play critical roles in development. Dysregulated CRE and SCRE activities have been reported to alter the expression of oncogenes and tumor suppressors, thereby regulating cancer hallmarks. To address the strong need for a comprehensive catalogue of dysregulated CREs and SCREs in human cancers, we present TSCRE (http://tscre.zsqylab.com/), an open resource providing tumor-specific and cell type-specific CREs and SCREs derived from the re-analysis of publicly available histone modification profiles. Currently, TSCRE contains 1 864 941 dysregulated CREs and 68 253 dysregulated SCREs identified from 1366 human patient samples spanning 17 different cancer types and 9 histone marks. Over 95% of these elements have been validated in public resources. TSCRE offers comprehensive annotations for each element, including associated genes, expression patterns, clinical prognosis, somatic mutations, transcript factor binding sites, cancer-type specificity, and drug response. Additionally, TSCRE integrates pathway and transcript factor enrichment analyses for each study, enabling in-depth functional and mechanistic investigations. Furthermore, TSCRE provides an interactive interface for users to explore any CRE and SCRE of interest. We believe TSCRE will be a highly valuable platform for the community to discover candidate cancer biomarkers.
Combined Lanreotide Autogel and Temozolomide Treatment of Progressive Pancreatic and Intestinal Neuroendocrine Tumors: The Phase II SONNET Study
Authors: Pavel Marianne , Lahner Harald , Hörsch Dieter , Rinke Anja , Denecke Timm , Koch Arend , Regnault Benjamin , Helbig Dorit , Hoffmanns Philipp , Raderer Markus
Published: January 2024

Background

In advanced neuroendocrine tumors (NET), antiproliferative treatment options beyond somatostatin analogs remain limited. Temozolomide (TMZ) has shown efficacy in NET alone or combined with other drugs.

Materials and Methods

SONNET (NCT02231762) was an open, multicenter, prospective, phase II study to evaluate lanreotide autogel 120 mg (LAN) plus TMZ in patients with progressive advanced/metastatic grade 1/2 gastroenteropancreatic (GEP) NET or of unknown primary. Patients could be enrolled at first-line or higher therapy line. The primary endpoint was disease control rate ([DCR], rate of stable disease [SD], partial [PR], and complete response [CR]) at 6 months of LAN and TMZ. Patients with nonfunctioning (NF) NET without progression at 6 months were randomized to 6-month LAN maintenance or watch and wait, patients with functioning (F)-NET with clinical benefit (PR, SD) continued on LAN.

Results

Fifty-seven patients were recruited. The majority of patients received the study drug at second or higher treatment line and had an NET G2. DCR at 6 months LAN and TMZ was 73.5%. After 6 months of further LAN maintenance, 54.5% of patients with F-NET and 71.4% with NF-NET had SD or PR vs 41.7% with NF-NET on observation only. LAN and TMZ were effective in all subgroups analyzed. At 12 months of follow-up, median progression-free survival was 11.1 months. Median serum chromogranin A decreased except in NF-NET on observation. O6-methylguanine DNA methyltransferase promoter methylation appeared to better reflect TMZ response than loss of gene expression. During combination therapy, the most frequent treatment-emergent adverse events grade 3/4 reported were nausea (14%), thrombocytopenia (12.3%), and neutropenia (8.8%). Four deaths were reported resulting from severe adverse events not considered related to study medication.

Conclusions

LAN plus TMZ is a treatment option for patients with progressive GEP-NET with more aggressive biological profile showing a manageable safety profile.
A Systematic Review of Clinical Applications of Anti-CD20 Radioimmunotherapy for Lymphoma
Authors: Durando Michael , Gopal Ajay K , Tuscano Joseph , Persky Daniel
Published: January 2024

Purpose

The clinical efficacy of anti-CD20 radioimmunotherapy (RIT) is due to a combination of extracellular mechanisms involving immune-mediated cytotoxicity, and intracellular mechanisms related to inhibition of CD20 signaling and DNA damage from ionizing radiation. In 2002, the first RIT was approved by the U.S. Food and Drug Administration for the treatment of patients with indolent B-cell follicular non-Hodgkin lymphoma (NHL). The 2 approved agents, 90 Y-ibritumomab tiuxetan (90Y-IT, Zevalin, Acrotech Biopharma) and 131 I-tositumomab (131-IT, Bexxar, GlaxoSmithKline) both target CD20. The aim of this study was to review the clinical applications and supporting clinical trial data of anti-CD20 RIT for lymphoma.

Methods

A review of published articles and abstracts on the clinical efficacy and safety of 90Y-IT and iodine I 131 tositumomab was performed.

Results

The clinical efficacy and safety of anti-CD20 RIT have been demonstrated in numerous clinical trials and case series. Agents have produced significant responses in patients with follicular NHLs and in off-label applications. Importantly, RIT has demonstrated promising findings in high-risk lymphomas and heavily pretreated and refractory patient populations. Associated toxicity profiles are noted as tolerable, acceptable, and most often reversible.

Conclusions

In the 2 decades since its approval, anti-CD20 RIT continues to demonstrate efficacy, particularly with a proportion of patients maintaining long-term remissions. The combination of prolonged efficacy, tolerability, and treatment convenience makes RIT a reasonable alternative to other systemic therapies. It is recommended that further research on RIT should focus on biomarkers of long-term response, pretargeting, and sequencing of RIT in the treatment course.
Solving inverse problems in physics by optimizing a discrete loss: Fast and accurate learning without neural networks
Authors: Karnakov Petr , Litvinov Sergey , Koumoutsakos Petros
Published: January 2024

In recent years, advances in computing hardware and computational methods have prompted a wealth of activities for solving inverse problems in physics. These problems are often described by systems of partial differential equations (PDEs). The advent of machine learning has reinvigorated the interest in solving inverse problems using neural networks (NNs). In these efforts, the solution of the PDEs is expressed as NNs trained through the minimization of a loss function involving the PDE. Here, we show how to accelerate this approach by five orders of magnitude by deploying, instead of NNs, conventional PDE approximations. The framework of optimizing a discrete loss (ODIL) minimizes a cost function for discrete approximations of the PDEs using gradient-based and Newton’s methods. The framework relies on grid-based discretizations of PDEs and inherits their accuracy, convergence, and conservation properties. The implementation of the method is facilitated by adopting machine-learning tools for automatic differentiation. We also propose a multigrid technique to accelerate the convergence of gradient-based optimizers. We present applications to PDE-constrained optimization, optical flow, system identification, and data assimilation. We compare ODIL with the popular method of physics-informed neural networks and show that it outperforms it by several orders of magnitude in computational speed while having better accuracy and convergence rates. We evaluate ODIL on inverse problems involving linear and nonlinear PDEs including the Navier–Stokes equations for flow reconstruction problems. ODIL bridges numerical methods and machine learning and presents a powerful tool for solving challenging, inverse problems across scientific domains.
Machine Learning as a Tool for Hypothesis Generation
Authors: Ludwig Jens , Mullainathan Sendhil
Published: January 2024

While hypothesis testing is a highly formalized activity, hypothesis generation remains largely informal. We propose a systematic procedure to generate novel hypotheses about human behavior, which uses the capacity of machine learning algorithms to notice patterns people might not. We illustrate the procedure with a concrete application: judge decisions about whom to jail. We begin with a striking fact: the defendant’s face alone matters greatly for the judge’s jailing decision. In fact, an algorithm given only the pixels in the defendant’s mug shot accounts for up to half of the predictable variation. We develop a procedure that allows human subjects to interact with this black-box algorithm to produce hypotheses about what in the face influences judge decisions. The procedure generates hypotheses that are both interpretable and novel: they are not explained by demographics (e.g., race) or existing psychology research, nor are they already known (even if tacitly) to people or experts. Though these results are specific, our procedure is general. It provides a way to produce novel, interpretable hypotheses from any high-dimensional data set (e.g., cell phones, satellites, online behavior, news headlines, corporate filings, and high-frequency time series). A central tenet of our article is that hypothesis generation is a valuable activity, and we hope this encourages future work in this largely “prescientific” stage of science.
Rare, Tightly-Bound, Multi-Cellular Clusters in the Pancreatic Ducts of Adult Mice Function Like Progenitor Cells and Survive and Proliferate After Acinar Cell Injury
Authors: Tremblay Jacob R , Ortiz Jose A , Quijano Janine C , Zook Heather N , Erdem Neslihan , LeBon Jeanne M , Li Wendong , Jou Kevin , Tsark Walter , Mann Jeffrey R , Kozlowski Mark T , Tirrell David A , Esni Farzad , Engle Dannielle D , Riggs Arthur D , Ku Hsun Teresa
Published: January 2024

Pancreatic ductal progenitor cells have been proposed to contribute to adult tissue maintenance and regeneration after injury, but the identity of such ductal cells remains elusive. Here, from adult mice, we identify a near homogenous population of ductal progenitor-like clusters, with an average of 8 cells per cluster. They are a rare subpopulation, about 0.1% of the total pancreatic cells, and can be sorted using a fluorescence-activated cell sorter with the CD133highCD71lowFSCmid-high phenotype. They exhibit properties in self-renewal and tri-lineage differentiation (including endocrine-like cells) in a unique 3-dimensional colony assay system. An in vitro lineage tracing experiment, using a novel HprtDsRed/+ mouse model, demonstrates that a single cell from a cluster clonally gives rise to a colony. Droplet RNAseq analysis demonstrates that these ductal clusters express embryonic multipotent progenitor cell markers Sox9, Pdx1, and Nkx6-1, and genes involved in actin cytoskeleton regulation, inflammation responses, organ development, and cancer. Surprisingly, these ductal clusters resist prolonged trypsin digestion in vitro, preferentially survive in vivo after a severe acinar cell injury and become proliferative within 14 days post-injury. Thus, the ductal clusters are the fundamental units of progenitor-like cells in the adult murine pancreas with implications in diabetes treatment and tumorigenicity.
Experimental and computational comparison of freeze–thaw-induced pressure generation in red and sugar maple
Authors: Zarrinderakht Maryam , Konrad Isabell , Wilmot Timothy R , Perkins Timothy D , van den Berg Abby K , Stockie John M
Published: January 2024

Sap exudation is the process whereby trees such as sugar (Acer saccharum Marsh.) and red maple (Acer rubrum L.) generate unusually high positive stem pressure in response to repeated cycles of freeze and thaw. This elevated xylem pressure permits the sap to be harvested over a period of several weeks and hence is a major factor in the viability of the maple syrup industry. The extensive literature on sap exudation documents competing hypotheses regarding the physical and biological mechanisms that drive positive pressure generation in maple, but to date, relatively little effort has been expended on devising mathematical models for the exudation process. In this paper, we utilize an existing model of Graf et al. (J Roy Soc Interface 12:20150665, 2015) that describes heat and mass transport within the multiphase gas–liquid–ice mixture in the porous xylem tissue. The model captures the inherent multiscale nature of xylem transport by including phase change and osmotic transport in wood cells on the microscale, which is coupled to heat transport through the tree stem on the macroscale. A parametric study based on simulations with synthetic temperature data identifies the model parameters that have greatest impact on stem pressure build-up. Measured daily temperature fluctuations are then used as model inputs and the resulting simulated pressures are compared directly with experimental measurements taken from mature red and sugar maple stems during the sap harvest season. The results demonstrate that our multiscale freeze–thaw model reproduces realistic exudation behavior, thereby providing novel insights into the specific physical mechanisms that dominate positive pressure generation in maple trees.
Prevalence and pattern of functional gastrointestinal disorders among secondary school adolescents in Lagos, Nigeria
Authors: Kumolu-Johnson Tolulope , Senbanjo Idowu Odunayo
Published: January 2024

Background

Limited data exist on functional gastrointestinal disorders (FGIDs) among sub-Saharan African children. This study aimed to determine FGID prevalence and pattern among secondary school adolescents in Lagos, Nigeria.

Methods

This descriptive cross-sectional study was conducted among adolescents aged 10–18 years in Isolo, Lagos, Nigeria from December 2020 to March 2021. A multi-stage sampling technique was used to select a total of 696 students from four secondary schools. Data were collected using a specifically designed questionnaire, the ROME IV questionnaire (QPGS-IV), and analyzed using the Statistical Package for the Social Sciences (SPSS) version 24.

Results

The mean age of the adolescents was 13.6 ± 2.1. A total of 221 (31.8%) adolescents fulfilled the criteria for at least one of the FGIDs. The most common FGIDs were functional constipation (10.1%), functional dyspepsia (9.4%) and abdominal migraine (8.6%). There was no significant difference in the overall prevalence of FGIDs between age groups (p = 0.07) and genders (p = 0.949). However, the prevalence of FGID sub-types showed that abdominal migraine, irritable bowel syndrome and functional non-retentive fecal incontinence were significantly higher in the age group 10–12 years (p = 0.045, p = 0.029 and p = 0.027, respectively) while only functional vomiting was significantly higher in male compared to female (p = 0.038).

Conclusion

FGIDs are common among adolescents in Lagos, Nigeria. The pattern of FGIDs shows similarities and differences with reports from other parts of the world. Healthcare workers must be aware of these disorders to provide optimal care.