bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing heterogeneity in spatial data using the HTA index with applications to spatial transcriptomics and imaging
Authors: Levy-Jurgenson Alona , Tekpli Xavier , Yakhini Zohar 
Published: August 2021

Abstract

Motivation
Tumour heterogeneity is being increasingly recognized as an important characteristic of cancer and as a determinant of prognosis and treatment outcome. Emerging spatial transcriptomics data hold the potential to further our understanding of tumour heterogeneity and its implications. However, existing statistical tools are not sufficiently powerful to capture heterogeneity in the complex setting of spatial molecular biology.

Results
We provide a statistical solution, the HeTerogeneity Average index (HTA), specifically designed to handle the multivariate nature of spatial transcriptomics. We prove that HTA has an approximately normal distribution, therefore lending itself to efficient statistical assessment and inference. We first demonstrate that HTA accurately reflects the level of heterogeneity in simulated data. We then use HTA to analyze heterogeneity in two cancer spatial transcriptomics datasets: spatial RNA sequencing by 10x Genomics and spatial transcriptomics inferred from H&E. Finally, we demonstrate that HTA also applies to 3D spatial data using brain MRI. In spatial RNA sequencing, we use a known combination of molecular traits to assert that HTA aligns with the expected outcome for this combination. We also show that HTA captures immune-cell infiltration at multiple resolutions. In digital pathology, we show how HTA can be used in survival analysis and demonstrate that high levels of heterogeneity may be linked to poor survival. In brain MRI, we show that HTA differentiates between normal ageing, Alzheimer’s disease and two tumours. HTA also extends beyond molecular biology and medical imaging, and can be applied to many domains, including GIS.

Availability and implementation
Python package and source code are available at: https://github.com/alonalj/hta.

Supplementary information
Supplementary data are available at Bioinformatics online.
Hippocampal Representations of Event Structure and Temporal Context during Episodic Temporal Order Memory
Authors: Liu Chuqi , Ye Zhifang , Chen Chuansheng , Axmacher Nikolai , Xue Gui 
Published: August 2021

Abstract
The hippocampus plays an important role in representing spatial locations and sequences and in transforming representations. How these representational structures and operations support memory for the temporal order of random items is still poorly understood. We addressed this question by leveraging the method of loci, a powerful mnemonic strategy for temporal order memory that particularly recruits hippocampus-dependent computations of spatial locations and associations. Applying representational similarity analysis to functional magnetic resonance imaging activation patterns revealed that hippocampal subfields contained representations of multiple features of sequence structure, including spatial locations, location distance, and sequence boundaries, as well as episodic-like temporal context. Critically, the hippocampal CA1 exhibited spatial transformation of representational patterns, showing lower pattern similarity for items in same locations than closely matched different locations during retrieval, whereas the CA23DG exhibited sequential transformation of representational patterns, showing lower pattern similarity for items in near locations than in far locations during encoding. These transformations enabled the encoding of multiple items in the same location and disambiguation of adjacent items. Our results suggest that the hippocampus can flexibly reconfigure multiplexed event structure representations to support accurate temporal order memory.
Real-World Comparison of Bezlotoxumab to Standard of Care Therapy for Prevention of Recurrent Clostridioides difficile Infection in Patients at High Risk for Recurrence
Authors: Johnson Tanner M , Molina Kyle C , Howard Amanda H , Schwarz Kerry , Allen Lorna , Huang Misha , Bajrovic Valida , Miller Matthew A 
Published: August 2021

Abstract

Background
Bezlotoxumab (BEZ) is a monoclonal antibody used to prevent recurrent Clostridioides difficile infection (rCDI). This study investigates BEZ effectiveness in relation to rCDI and patient-specific risk factors in a real-world setting.

Methods
A matched, retrospective cohort study was conducted from 2015 to 2019 to compare BEZ to historical standard of care (SoC) therapy with vancomycin or fidaxomicin. The primary outcome was incidence of 90-day rCDI. Secondary outcomes were incidence of all-cause hospital readmission and all-cause mortality at 90 days, infusion-related reactions, and incidence of heart failure exacerbation. Baseline confounding was addressed using inverse probability of treatment weighting (IPTW).

Results
Overall, 107 participants were included (54 BEZ and 53 SoC). Mean number of prior CDI episodes was 2, median number of risk factors for rCDI was 4, and 28% of participants had severe CDI. Incidence of 90-day rCDI was 11% BEZ vs 43% SoC (P = &lt; .001) and 90-day all-cause readmission was 40% BEZ vs 64% SoC (P = .011). In IPTW-adjusted analyses, BEZ was associated with significantly reduced odds of rCDI (odds ratio [OR], 0.14 [95% confidence interval {CI}: .05–.41]) and all-cause readmission (OR, 0.36 [95% CI: .16–.81]). No safety signals were detected with BEZ use.

Conclusions
BEZ is effective for the prevention of rCDI and reduction in all-cause hospital readmission for patients at high risk for recurrence, supporting current guideline recommendations.
The Natural History of Rectal Gonococcal and Chlamydial Infections: The ExGen Study
Authors: Barbee Lindley A , Khosropour Christine M , Soge Olusegun O , Hughes James P , Haglund Micaela , Yeung Winnie , Golden Matthew R 
Published: August 2021

Abstract

Background
The duration of rectal gonococcal and chlamydial infection remains unknown. This basic epidemiologic parameter is needed to understand transmission dynamics.

Methods
We conducted a prospective, longitudinal, observational cohort study of 140 men who have sex with men (MSM) at risk of gonorrhea and chlamydia acquisition. For 48 weeks, enrolled men collected rectal swabs (Aptima multi-test kit) at home and responded to an electronic survey about sexual behavior and health conditions weekly. Swabs remained untested until participants completed the study. We used Kaplan-Meier estimates to determine the median duration of infection, censoring infections for treatment, loss to follow-up, and end-of-study. We used log-rank test to compare duration of infection by human immunodeficiency virus (HIV) status, history of infection with gonorrhea or chlamydia, and coinfection with the other pathogen.

Results
140 enrolled MSM contributed 70.5 person-years of follow-up. Eighteen men had 20 incident rectal gonococcal infections, which persisted for 2–23 weeks; 30% were censored for treatment. The estimated median duration of rectal gonorrhea was 9 weeks (95% confidence interval [CI]: 3–12 weeks). Twenty-four men experienced 32 rectal chlamydial infections, persisting between 2 and 42 weeks; 60% were censored. The estimated duration of rectal chlamydia was 13 weeks (95% CI: 6 weeks–undefined). There were no differences in the duration of rectal gonorrhea or chlamydia by HIV status, history of chlamydia/gonorrhea, or coinfection.

Conclusions
On average, rectal gonorrhea and chlamydial infections last 2–3 months, although some infections persisted for 6–11 months. Further understanding into predictors of persistence is needed.
Effectiveness of Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccines for Preventing Coronavirus Disease 2019 Hospitalizations in the United States
Authors: Tenforde Mark W , Patel Manish M , Ginde Adit A , Douin David J , Talbot H Keipp , Casey Jonathan D , Mohr Nicholas M , Zepeski Anne , Gaglani Manjusha , McNeal Tresa , Ghamande Shekhar , Shapiro Nathan I , Gibbs Kevin W , Files D Clark , Hager David N , Shehu Arber , Prekker Matthew E , Erickson Heidi L , Exline Matthew C , Gong Michelle N , Mohamed Amira , Henning Daniel J , Steingrub Jay S , Peltan Ithan D , Brown Samuel M , Martin Emily T , Monto Arnold S , Khan Akram , Hough Catherine L , Busse Laurence W , ten Lohuis Caitlin C , Duggal Abhijit , Wilson Jennifer G , Gordon Alexandra June , Qadir Nida , Chang Steven Y , Mallow Christopher , Gershengorn Hayley B , Babcock Hilary M , Kwon Jennie H , Halasa Natasha , Chappell James D , Lauring Adam S , Grijalva Carlos G , Rice Todd W , Jones Ian D , Stubblefield William B , Baughman Adrienne , Womack Kelsey N , Lindsell Christopher J , Hart Kimberly W , Zhu Yuwei , Olson Samantha M , Stephenson Meagan , Schrag Stephanie J , Kobayashi Miwako , Verani Jennifer R , Self Wesley H ,   Influenza and Other Viruses in the Acutely Ill (IVY) Network
Published: August 2021

Abstract

Background
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination coverage increases in the United States, there is a need to understand the real-world effectiveness against severe coronavirus disease 2019 (COVID-19) and among people at increased risk for poor outcomes.

Methods
In a multicenter case-control analysis of US adults hospitalized March 11–May 5, 2021, we evaluated vaccine effectiveness to prevent COVID-19 hospitalizations by comparing odds of prior vaccination with a messenger RNA (mRNA) vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with COVID-19 and hospital-based controls who tested negative for SARS-CoV-2.

Results
Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B0.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of 2 vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% confidence interval [CI], 80.7–91.3). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18–49 years (97.4%; 95% CI, 79.3–9.7). Among 45 patients with vaccine-breakthrough COVID hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI,20.8–82.6) than without immunosuppression (91.3%; 95% CI, 85.6–94.8).

Conclusion
During March–May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing COVID-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.
An Empirical Procedure to Evaluate Misinformation Rejection and Deception in Mediated Communication Contexts
Authors: Paquin Ryan S , Boudewyns Vanessa , Betts Kevin R , Johnson Mihaela , O’Donoghue Amie C , Southwell Brian G 
Published: August 2021

Abstract
Although misleading health information is not a new phenomenon, no standards exist to assess consumers’ ability to detect and subsequently reject misinformation. Part of this deficit reflects theoretical and measurement challenges. After drawing novel connections among legal, regulatory, and philosophical perspectives on false, misleading or deceptive advertising and cognitive-process models of persuasive communication, we define deception and misinformation rejection. Recognizing that individuals can hold beliefs that align with a persuasive message without those beliefs having been influenced by it, we derive empirical criteria to test for evidence of these constructs that center on yielding or not yielding to misinformation in mediated contexts. We present data from an experimental study to illustrate the proposed test procedure and provide evidence for two theoretically derived patterns indicative of misinformation rejection. The resulting definitions and empirical procedure set the stage for additional theorizing and empirical studies on misinformation in the marketplace.
The Phenotypic Spectrum of New-onset IBD in Canadian Children of South Asian Ethnicity: A Prospective Multi-Centre Comparative Study
Authors: Dhaliwal J , Carroll M W , deBruyn J C , Ricciuto A , Benchimol E I , Lawrence S , Sherlock M , El-Matary W , Brill H , Church P , Wine E , Carman N , Muise A , Huynh H , Mack D R , Walters T D , Griffiths A M , Jacobson K 
Published: August 2021

Abstract

Background
Canadian-born children of South Asian [SA] ethnicity develop inflammatory bowel disease [IBD] at similar rates to those among Caucasian children. We evaluated the variation in phenotypic spectrum of IBD in SA and Caucasian children in a national paediatric inception cohort of new-onset IBD.

Methods
Patients aged &lt;17 years, enrolled in a Canadian nationwide inception cohort study, were included. Baseline demographic and IBD phenotypic features were compared between SA and Caucasian children. Longitudinal outcomes through 18 months of follow-up were compared matched by propensity scores.

Results
Of 1156 children enrolled over 2014 to 2019, 623 were Caucasian [98% and 88% parents Canadian born] and 114 SA [79% Canadian born, 87% parents SA born]. Fewer SAs have a first-degree relative with IBD, 6% vs 19% in Caucasians, p = 0.002. SAs present at a younger age, median age 11.4 years (interquartile range [IQR] 9.2–14.3) vs 13 years [IQR 10.9-15 years], p = 0.03 and more commonly with a UC/IBD-U [ulcerative colitis/IBD-unclassified] subtype [ratio of UC/IBD-U to CD 1.2:1 vs 1:1.8 for Caucasians, p &lt;0.001]. Additionally, a greater proportion of SA CD patients present with colonic-only disease [colonic-only CD/UC/IBD-U in SAs 67% vs 57% for Caucasians, p = 0.001], and among those with CD, colonic CD in SAs 31% vs 23% in Caucasians, p = 0.20]. Perianal fistulising disease was also numerically more common in SAs (14 [27%] vs 64 [18%], p = 0.06]. Adjusting for differences in phenotypic presentation, anti-tumour necrosis factor [TNF] exposure, and time to initiation was similar, and two-thirds of children, whether anti-TNF exposed or naïve, were in corticosteroid-free clinical remission at 18 months irrespective of ethnicity.

Conclusions
The phenotypic spectrum of new-onset IBD in SA children differs from that of Caucasian children, but treatment and clinical course are similar within phenotypic subgroups.
Bacillus subtilis strain BS06 protects soybean roots from Fusarium oxysporum infection
Authors: Jia Yujing , Huang Jingxin , Qi Lanlan , Zhang Xiaole , Liu Jianhong , Guan Huilin , Wang Chenjiao , Tang Guangmei , Dou Xiaolin , Lu Meng 
Published: August 2021

ABSTRACT
Soybean, as a major oil crop, is one of the most widely planted crops in the world. Fusarium oxysporum causes soybean root rot, leading to great economic losses to soybean planting every year globally. Chemical fungicide for controlling soybean F. oxysporum diseases may cause environmental problems and has human health risks. Biological control methods avoid these shortcomings; however, few studies have focused on biocontrol of soybean diseases caused by F. oxysporum. Aiming at this problem, we obtained biocontrol bacteria against soybean F. oxysporum by plate confrontation method. The type of the strain with the highest biocontrol activity was identified by molecular biological methods, and then its biocontrol effects were verified through greenhouse experiments. One of our isolated strain named BS06 strain had the highest activity, which was identified as Bacillus subtilis. Our study showed that BS06 strain could effectively control soybean F. oxysporum disease and significantly reduce F. oxysporum to infect soybean roots. Compared with control and carbendazim treatments, BS06 treatment had higher root biomass, plant height, leaf chlorophyll content, stem base diameter and control efficiency. Our results indicated that BS06 could effectively protect soybean root (BS06 strain might produce substances to inhibit F. oxysporum), which was potentially useful for soybean planting.
Disruption ofECM33in diploid wine yeast EC1118: cell morphology and aggregation and their influence on fermentation performance
Authors: Lang Tom A , Walker Michelle E , Jiranek Vladimir 
Published: August 2021

ABSTRACTWhen investigating yeast gene function in relation to fermentation, many screens rely on haploid yeast derivatives. This, however, is not representative of industrial strains, which are typically diploid. One such example is the disruption of ECM33, which was associated with improved fermentation in the haploid wine yeast C911D, but remains uncharacterised in a diploid industrial strain background. We report on the homozygous disruption of ECM33 in Lalvin EC1118 using CRISPR/Cas9. EC1118 ecm33 resulted in a reduction of fermentation duration in a defined medium with limiting and sufficient nitrogen (−20% and −13%, respectively) when shaken. Increased cell size and aggregation, a phenotype previously unidentified in ecm33∆ as haploid yeast tend to aggregate, was also observed. This phenotype led to premature settling thereby the yeast behaving similarly to EC1118 in wine-like semi-static fermentations in a chemically defined medium. Further assessment in semi-static Riesling and Chardonnay fermentations inoculated based on cell number or biomass resulted in no significant difference or significantly slower fermentation duration in comparison the EC1118, nullifying the benefits of this mutation unless agitation is applied. This study draws attention to phenotypes being condition-dependent, highlighting the need to characterise and verify fermentation efficiency mutations in industrial yeast.
Continuous cover forestry in Europe: usage and the knowledge gaps and challenges to wider adoption
Authors: Mason W L , Diaci J , Carvalho J , Valkonen S 
Published: August 2021

Abstract
There is increasing interest across Europe in adopting forest management strategies, which promote species and structural diversity through the use of irregular silvicultural systems, an approach often described as continuous cover forestry (CCF). However, there is little information about the proportion of CCF practised across the continent or about the knowledge gaps and other obstacles that limit its use. A survey of respondents in 33 European countries sought to address these issues. The results indicated that the silvicultural systems associated with CCF were single stem, group selection and irregular shelterwood. Rotational forest management (RFM) was more frequent than CCF in about 66 per cent of countries, whereas in 25 per cent the reverse was true. We estimated that between 22 and 30 per cent of European forests are managed through CCF, although good data are lacking. The main knowledge gaps were: uncertainties arising from climate change (e.g. appropriate species choice, carbon storage in CCF), using CCF to increase forest resilience, deployment of mechanized harvesting systems, lack of knowledge about CCF amongst professional foresters and better information on economic implications of this approach. Major obstacles included: little awareness of CCF amongst forest owners, limited competence in CCF within the forestry profession and a scarcity of skilled forest workers to implement this approach, high ungulate populations damaging natural regeneration, a sawmilling sector geared to processing medium-sized logs, subsidy regimes favouring practices associated with RFM and a lack of experience in transforming plantation forests to more diverse structures. Better information on the use of different silvicultural systems is essential to allow policymakers and other stakeholders to monitor progress in diversifying forests. Establishment of a continental network of long-term operational trials (e.g. expanding the existing Association Futaie Irrégulière network) would improve professional understanding of CCF, would demonstrate this approach to forest owners and other stakeholders and could provide a valuable platform for supporting research.
International Trade, Cooperation, and Conflict: The Role of Institutions and Capabilities
Authors: Peterson Timothy M , Wen Shaoshuang 
Published: August 2021

AbstractIn this paper, we reconcile divergent theories linking trade to conflict—opportunity costs and costly signaling on the one hand versus dependence and coercion on the other hand. We argue that variation in domestic political institutions and state capabilities can condition how international trade affects conflictual or cooperative political relationships. When institutions result in a more nationally representative constituency, trade has a relatively more negative association with conflict, whereas deviation from this institutional arrangement reduces the pacifying impact of trade. The presence of greater military capabilities incentivizes leaders to use trade as a lever to advance other state interests. As such, for more powerful states, trade is associated with relatively more conflict and cooperation. We find support for our expectations in statistical tests spanning 1994–2012.
Interplay between extreme drift and selection intensities favors the fixation of beneficial mutations in selfing maize populations
Authors: Desbiez-Piat Arnaud , Le Rouzic Arnaud , Tenaillon Maud I , Dillmann Christine 
Published: August 2021

Abstract
Population and quantitative genetic models provide useful approximations to predict long-term selection responses sustaining phenotypic shifts, and underlying multilocus adaptive dynamics. Valid across a broad range of parameters, their use for understanding the adaptive dynamics of small selfing populations undergoing strong selection intensity (thereafter High Drift-High selection regime, HDHS) remains to be explored. Saclay Divergent Selection Experiments (DSEs) on maize flowering time provide an interesting example of populations evolving under HDHS, with significant selection responses over 20 generations in two directions. We combined experimental data from Saclay DSEs, forward individual-based simulations, and theoretical predictions to dissect the evolutionary mechanisms at play in the observed selection responses. We asked two main questions: How do mutations arise, spread, and reach fixation in populations evolving under HDHS? How does the interplay between drift and selection influence observed phenotypic shifts? We showed that the long-lasting response to selection in small populations is due to the rapid fixation of mutations occurring during the generations of selection. Among fixed mutations, we also found a clear signal of enrichment for beneficial mutations revealing a limited cost of selection. Both environmental stochasticity and variation in selection coefficients likely contributed to exacerbate mutational effects, thereby facilitating selection grasp and fixation of small-effect mutations. Together our results highlight that despite a small number of polymorphic loci expected under HDHS, adaptive variation is continuously fueled by a vast mutational target. We discuss our results in the context of breeding and long-term survival of small selfing populations.