bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomisation inference beyond the sharp null: bounded null hypotheses and quantiles of individual treatment effects
Authors: Caughey Devin , Dafoe Allan , Li Xinran , Miratrix Luke 
Published: August 2023

Abstract
Randomisation inference (RI) is typically interpreted as testing Fisher’s ‘sharp’ null hypothesis that all unit-level effects are exactly zero. This hypothesis is often criticised as restrictive and implausible, making its rejection scientifically uninteresting. We show, however, that many randomisation tests are also valid for a ‘bounded’ null hypothesis under which the unit-level effects are all non-positive (or all non-negative) but are otherwise heterogeneous. In addition to being more plausible a priori, bounded nulls are closely related to substantively important concepts such as monotonicity and Pareto efficiency. Reinterpreting RI in this way expands the range of inferences possible in this framework. We show that exact confidence intervals for the maximum (or minimum) unit-level effect can be obtained by inverting tests for a sequence of bounded nulls. We also generalise RI to cover inference for quantiles of the individual effect distribution as well as for the proportion of individual effects larger (or smaller) than a given threshold. The proposed confidence intervals for all effect quantiles are simultaneously valid, in the sense that no correction for multiple analyses is required. In sum, our reinterpretation and generalisation provide a broader justification for randomisation tests and a basis for exact non-parametric inference for effect quantiles.
Diversity of virulence and antibiotic resistance genes expressed in Class A biosolids and biosolids-amended soil as revealed by metatranscriptomic analysis
Authors: D’Angelo Elisa Marie 
Published: August 2023

Abstract
Class A biosolids is a treated sewage sludge, commonly applied to agricultural fields, home lawns/gardens, golf courses, forests, and remediation sites around the world. This practice is of public and agricultural concern due to the possibility that biosolids contain antibiotic-resistant bacteria and fungal pathogens that could persist for extended periods in soil. This possibility was determined by metatranscriptomic analysis of virulence, antibiotic resistance, and plasmid conjugation genes, a Class A biosolids, organically managed soil, and biosolids-amended soil under realistic conditions. Biosolids harbored numerous transcriptionally active pathogens, antibiotic resistance genes, and conjugative genes that annotated mostly to Gram-positive pathogens of animal hosts. Biosolids amendment to soil significantly increased the expression of virulence genes by numerous pathogens and antibiotic-resistant genes that were strongly associated with biosolids. Biosolids amendment also significantly increased the expression of virulence genes by native soil fungal pathogens of plant hosts, which suggests higher risks of crop damage by soil fungal pathogens in biosolids-amended soil. Although results are likely to be different in other soils, biosolids, and microbial growth conditions, they provide a more holistic, accurate view of potential health risks associated with biosolids and biosolids-amended soils than has been achievable with more selective cultivation and PCR-based techniques.
Fermi LAT AGN classification using supervised machine learning
Authors: Cooper Nathaniel , Dainotti Maria Giovanna , Narendra Aditya , Liodakis Ioannis , Bogdan Malgorzata 
Published: August 2023

ABSTRACT
Classifying active galactic nuclei (AGNs) is a challenge, especially for BL Lacertae objects (BLLs), which are identified by their weak emission line spectra. To address the problem of classification, we use data from the fourth Fermi Catalog, Data Release 3. Missing data hinder the use of machine learning to classify AGNs. A previous paper found that Multivariate Imputation by Chain Equations (MICE) imputation is useful for estimating missing values. Since many AGNs have missing redshift and the highest energy, we use data imputation with MICE and k-nearest neighbours (kNN) algorithm to fill in these missing variables. Then, we classify AGNs into the BLLs or the flat spectrum radio quasars (FSRQs) using the SuperLearner, an ensemble method that includes several classification algorithms like logistic regression, support vector classifiers, Random Forest, Ranger Random Forest, multivariate adaptive regression spline (MARS), Bayesian regression, and extreme gradient boosting. We find that a SuperLearner model using MARS regression and Random Forest algorithms is 91.1 per cent accurate for kNN-imputed data and 91.2 per cent for MICE-imputed data. Furthermore, the kNN-imputed SuperLearner model predicts that 892 of the 1519 unclassified blazars are BLLs and 627 are FSRQs, while the MICE-imputed SuperLearner model predicts 890 BLLs and 629 FSRQs in the unclassified set. Thus, we can conclude that both imputation methods work efficiently and with high accuracy and that our methodology ushers the way for using SuperLearner as a novel classification method in the AGN community and, in general, in the astrophysics community.
X-ray emission from pre-main sequence stars with multipolar magnetic fields
Authors: Stuart Kieran A , Gregory Scott G 
Published: August 2023

ABSTRACT
The large-scale magnetic fields of several pre-main sequence (PMS) stars have been observed to be simple and axisymmetric, dominated by tilted dipole and octupole components. The magnetic fields of other PMS stars are highly multipolar and dominantly non-axisymmetric. Observations suggest that the magnetic field complexity increases as PMS stars evolve from Hayashi to Henyey tracks in the Hertzsprung–Russell diagram. Independent observations have revealed that X-ray luminosity decreases with age during PMS evolution, with Henyey track PMS stars having lower fractional X-ray luminosities (LX/L*) compared to Hayashi track stars. We investigate how changes in the large-scale magnetic field topology of PMS stars influences coronal X-ray emission. We construct coronal models assuming pure axisymmetric multipole magnetic fields, and magnetic fields consisting of a dipole plus an octupole component only. We determine the closed coronal emitting volume, over which X-ray-emitting plasma is confined, using a pressure balance argument. From the coronal volumes, we determine X-ray luminosities. We find that LX decreases as the degree ℓ of the multipole field increases. For dipole plus octupole magnetic fields, we find that LX tends to decrease as the octupole component becomes more dominant. By fixing the stellar parameters at values appropriate for a solar mass PMS star, varying the magnetic field topology results in two orders of magnitude variation in LX. Our results support the idea that the decrease in LX as PMS stars age can be driven by an increase in the complexity of the large-scale magnetic field.
FRB 20121102A: images of the bursts and the varying radio counterpart
Authors: Rhodes L , Caleb M , Stappers B W , Andersson A , Bezuidenhout M C , Driessen L N , Heywood I 
Published: August 2023

ABSTRACT
As more Fast Radio Bursts (FRBs) are being localized, we are learning that some fraction have persistent radio sources (PRSs). Such a discovery motivates an improvement in our understanding of the nature of those counterparts, the relation to the bursts themselves and why only some FRBs have PRSs. We report on observations made of FRB 20121102A with the MeerKAT radio telescope. Across five epochs, we detect the PRS associated with FRB 20121102A. Our observations are split into a cluster of four epochs (MJD 58732–58764) and a separate single epoch about 1000 d later. The measured flux density is constant across the first four observations but then decays by more than one-third in the final observation. Our observations on MJD 58736 coincided with the detections of 11 bursts from FRB 20121102A by the MeerTRAP backend, seven of which we detected in the image plane. We discuss the importance of image plane detections when considering the commensal transient searches being performed with MeerKAT and other radio facilities. We find that MeerKAT is so sensitive that within a 2-s image, we can detect any FRB with a flux density above 2.4 mJy at 1.3 GHz and so could localize every FRB that has been detected by CHIME to date.
Star cluster progenitors are dynamically decoupled from their parent molecular clouds
Authors: Peretto Nicolas , Rigby Andrew J , Louvet Fabien , Fuller Gary A , Traficante Alessio , Gaudel Mathilde 
Published: August 2023

ABSTRACT
The formation of stellar clusters dictates the pace at which galaxies evolve, and solving the question of their formation will undoubtedly lead to a better understanding of the Universe as a whole. While it is well known that star clusters form within parsec-scale overdensities of interstellar molecular gas called clumps, it is, however, unclear whether these clumps represent the high-density tip of a continuous gaseous flow that gradually leads towards the formation of stars, or a transition within the gas physical properties. Here, we present a unique analysis of a sample of 27 infrared dark clouds embedded within 24 individual molecular clouds that combine a large set of observations, allowing us to compute the mass and velocity dispersion profiles of each, from the scale of tens of parsecs down to the scale of tenths of a parsec. These profiles reveal that the vast majority of the clouds, if not all, are consistent with being self-gravitating on all scales, and that the clumps, on parsec-scale, are often dynamically decoupled from their surrounding molecular clouds, exhibiting steeper density profiles (ρ∝r−2) and flat velocity dispersion profiles (σ∝r0), clearly departing from Larson’s relations. These findings suggest that the formation of star clusters correspond to a transition regime within the properties of the self-gravitating molecular gas. We propose that this transition regime is one that corresponds to the gravitational collapse of parsec-scale clumps within otherwise stable molecular clouds.
Investigating the energy-dependent temporal nature of black hole binary system H 1743-322
Authors: Husain Nazma , Garg Akash , Misra Ranjeev , Sen Somasri 
Published: August 2023

ABSTRACT
Black hole X-ray binaries routinely exhibit quasi-periodic oscillations (QPOs) in their power density spectrum. Studies of QPOs have demonstrated immense ability to understand these dynamical systems although their unambiguous origin still remains a challenge. We investigate the energy-dependent properties of the Type-C QPOs detected for H 1743-322 as observed with AstroSat in its two X-ray outbursts of 2016 and 2017. The combined broad-band LAXPC and SXT spectrum is well modelled with a soft thermal and a hard Comptonization component. The QPO exhibits soft/negative lags i.e. variation in soft-band lags the variation in hard band, although the upper harmonic shows opposite behaviour i.e. hard/positive lags. Here, we model energy-dependent properties (fractional root mean square and time-lag variation with energy) of the QPO and its upper harmonic individually with a general scheme that fits these properties by utilizing the spectral information and consequently allows to identify the radiative component responsible for producing the variability. Considering the truncated disc picture of accretion flow, a simple model with variation in inner disc temperature, heating rate, and fractional scattering with time delays is able to describe the fractional rms and time-lag spectra. In this work, we show that this technique can successfully describe the energy-dependent features and identify the spectral parameters generating the variability.
Phase Ib/II Study of the Efficacy and Safety of Binimetinib (MEK162) Plus Panitumumab for Mutant or Wild-Type RAS Metastatic Colorectal Cancer
Authors: Van Cutsem Eric , Yaeger Rona , Delord Jean-Pierre , Tabernero Josep , Siu Lillian L , Ducreux Michel , Siena Salvatore , Elez Elena , Kasper Stefan , Zander Thomas , Steeghs Neeltje , Murphy Danielle , Edwards Michelle , Wainberg Zev A 
Published: August 2023

Abstract

Introduction
Activating RAS gene mutations occur in approximately 55% of patients with metastatic colorectal cancer (mCRC) and are associated with poorer clinical outcomes due to epidermal growth factor receptor (EGFR) blockade resistance. Combined EGFR and mitogen-activated protein kinase (MEK) inhibition may extend response to EGFR inhibition and overcome acquired resistance. This phase Ib/II dose escalation trial evaluated the safety and activity of dual inhibition with binimetinib (MEK1/2 inhibitor) and panitumumab (EGFR inhibitor [EGFRi]) in patients with RAS mutant or BRAF wild type (WT)/RAS WT mCRC.

Methods
Phase Ib dose escalation started with binimetinib 45 mg twice daily plus panitumumab 6 mg/kg administered every 2 weeks. In the phase II study, patients with measurable mCRC were enrolled into 4 groups based on previous anti-EGFR monoclonal antibody therapy and RAS mutational status.

Results
No patients in the phase Ib portion (n = 10) had a response; 70% of patients had stable disease. In the phase II portion (n = 43), overall response rate (ORR, confirmed) was 2.3% with one partial response in the RAS WT group, DCR was 30.2%, and median progression-free survival was 1.8 months (95%CI, 1.6-3.3). All patients experienced ≥1 adverse event, with the most common being diarrhea (71.7%), vomiting (52.8%), nausea (50.9%), fatigue (49.1%), dermatitis acneiform (43.4%), and rash (41.5%). Most patients required treatment interruption or dose reduction due to difficulties tolerating treatment.

Conclusions
The combination of binimetinib and panitumumab had substantial toxicity and limited clinical activity for patients with mutant or WT RAS mCRC, independent of EGFRi treatment history (Trial registration: NCT01927341).
The Evolving Landscape of Immune Checkpoint Inhibitors and Antibody Drug Conjugates in the Treatment of Early-Stage Breast Cancer
Authors: Bhardwaj Prarthna V , Abdou Yara G 
Published: August 2023

Abstract
For decades, chemotherapy has been the mainstay of breast cancer treatment. Novel therapies are expanding the therapeutic options and altering the treatment algorithms to manage this disease. The use and approval of immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) represent a few areas of progress. These therapies initially gained attention in the metastatic setting but have subsequently found a role in early-stage breast cancer. Although human epidermal growth factor receptor 2 (HER2) is at the center of ADC development, other surface antigens with a differential expression between tumor and normal cells may be appropriate for ADC targeting. This has led to the discovery of new ADCs targeting other receptors, including TROP-2, HER-3, and LIV-1, to name a few. Similarly, the addition of pembrolizumab in treating early-stage triple-negative breast cancer has led to exploring other ICIs in this setting. However, it has also raised important scientific questions regarding optimal patient selection, biomarkers that predict the success of ICIs, ideal chemotherapy partners, and the financial implications of bringing newer therapies to the forefront. In this review, we discuss the evolving landscape of ICIs and ADCs in managing early-stage breast cancer and provide an overview of potential future advancement in the field.
An experimental study on how accents affect public perceptions of the police
Authors: He Mu , Yang Anting , Lu Jiahui , Shi Chen 
Published: August 2023

Abstract
Public perceptions of the police have profound impact on public–police relations and the effectiveness of policing practices. Previous research on public perceptions of the police has focussed on citizens’ socio-demographic profile (e.g. age, race) and police officers’ visual characteristics (e.g. attire), but scant attention has been paid to the impact of accent. The purpose of this research is to investigate the effect of accent on perceptions of the police. In a matched-guise experiment, 160 participants rated officers on their police professional and aesthetic traits after listening to their speeches performed in standard Chinese versus Chinese with a regional accent. The results showed that police officers were rated higher on all the traits when they spoke standard Chinese than accented Chinese, and gender may play a moderating role. The present study revealed that accent can be powerful in affecting the public image of the police.
Pathogen Profile of Klebsiella variicola, the Causative Agent of Banana Sheath Rot
Authors: Sun Yunhao , Zheng Chuanyuan , Zhou Jianuan , Zhen Meng , Wei Xingying , Yan Xun , Guo Xiaojian , Zheng Li , Shao Mingwei , Li Chunji , Qin Di , Zhang Jie , Xiong Lina , Xing Juejun , Huang Bingzhi , Dong Zhangyong , Cheng Ping , Yu Guohui 
Published: August 2023

Banana (Musa spp.) is an important fruit and food crop worldwide. In recent years, banana sheath rot has become a major problem in banana cultivation, causing plant death and substantial economic losses. Nevertheless, the pathogen profile of this disease has not been fully characterized. Klebsiella variicola is a versatile bacterium capable of colonizing different hosts, such as plants, humans, insects, and animals, and is recognized as an emerging pathogen in various hosts. In this study, we obtained 12 bacterial isolates from 12 different banana samples showing banana sheath rot in Guangdong and Guangxi Provinces, China. Phylogenetic analysis based on 16S rRNA sequences confirmed that all 12 isolates were K. variicola strains. We sequenced the genomes of these strains, performed comparative genomic analysis with other sequenced K. variicola strains, and found a lack of consistency in accessory gene content among these K. variicola strains. However, prediction based on the pan-genome of K. variicola revealed 22 unique virulence factors carried by the 12 pathogenic K. variicola isolates. Microbiome and microbial interaction network analysis of endophytes between the healthy tissues of diseased plants and healthy plants of two cultivars showed that Methanobacterium negatively interacts with Klebsiella in banana plants and that Herbaspirillum might indirectly inhibit Methanobacterium to promote Klebsiella growth. These results suggest that banana sheath rot is caused by the imbalance of plant endophytes and opportunistic pathogenic bacteria, providing an important basis for research and control of this disease. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
HIF‐1α inhibition in macrophages preserves acute liver failure by reducing IL‐1β production
Authors: Kong Xiangrong , Liu Wei , Zhang Xinwen , Zhou Chendong , Sun Xinyu , Cheng Long , Lin Jinxia , Xie Zhifu , Li Jingya 
Published: August 2023

AbstractThe development of acute liver failure (ALF) is dependent on its local inducer. Inflammation is a high‐frequency and critical factor that accelerates hepatocyte death and liver failure. In response to injury stress, the expression of the transcription factor hypoxia‐inducible factor‐1α (HIF‐1α) in macrophages is promoted by both oxygen‐dependent and oxygen‐independent mechanisms, thus promoting the expression and secretion of the cytokine interleukin‐1β (IL‐1β). IL‐1β further induces hepatocyte apoptosis or necrosis by signaling through the receptor (IL‐1R) on hepatocyte. HIF‐1α knockout in macrophages or IL‐1R knockout in hepatocytes protects against liver failure. However, whether HIF‐1α inhibition in macrophages has a protective role in ALF is unclear. In this study, we revealed that the small molecule HIF‐1α inhibitor PX‐478 inhibits the expression and secretion of IL‐1β, but not tumor necrosis factor α (TNFα), in bone marrow‐derived macrophages (BMDMs). PX‐478 pretreatment alleviates liver injury in LPS/D‐GalN‐induced ALF mice by decreasing the hepatic inflammatory response. In addition, preventive or therapeutic administration of PX‐478 combined with TNFα neutralizing antibody markedly improved LPS/D‐GalN‐induced ALF. Taken together, our data suggest that PX‐478 administration leads to HIF‐1α inhibition and decreased IL‐1β secretion in macrophages, which represents a promising therapeutic strategy for inflammation‐induced ALF.
Deoxyribonucleoside treatment rescues EtBr‐induced mtDNA depletion in iPSC‐derived neural stem cells with POLG mutations
Authors: Kristiansen Cecilie Katrin , Furriol Jessica , Chen Anbin , Sullivan Gareth John , Bindoff Laurence A. , Liang Kristina Xiao 
Published: August 2023

AbstractMutations in POLG, the gene encoding the catalytic subunit of the mitochondrial DNA (mtDNA) polymerase gamma (Pol‐γ), lead to diseases driven by defective mtDNA maintenance. Despite being the most prevalent cause of mitochondrial disease, treatments for POLG‐related disorders remain elusive. In this study, we used POLG patient‐induced pluripotent stem cell (iPSC)‐derived neural stem cells (iNSCs), one homozygous for the POLG mutation c.2243G>C and one compound heterozygous with c.2243G>C and c.1399G>A, and treated these iNSCs with ethidium bromide (EtBr) to study the rate of depletion and repopulation of mtDNA. In addition, we investigated the effect of deoxyribonucleoside (dNs) supplementation on mtDNA maintenance during EtBr treatment and post‐treatment repopulation in the same cells. EtBr‐induced mtDNA depletion occurred at a similar rate in both patient and control iNSCs, however, restoration of mtDNA levels was significantly delayed in iNSCs carrying the compound heterozygous POLG mutations. In contrast, iNSC with the homozygous POLG mutation recovered their mtDNA at a rate similar to controls. When we treated cells with dNs, we found that this reduced EtBr‐induced mtDNA depletion and significantly increased repopulation rates in both patient iNSCs. These observations are consistent with the hypothesis that mutations in POLG impair mtDNA repopulation also within intact neural lineage cells and suggest that those with compound heterozygous mutation have a more severe defect of mtDNA synthesis. Our findings further highlight the potential for dNs to improve mtDNA replication in the presence of POLG mutations, suggesting that this may offer a new therapeutic modality for mitochondrial diseases caused by disturbed mtDNA homeostasis.