bluuebunny/crossref_metadata_2025 huggingface dataset:
PRELIMINARY SAFETY, EFFICACY AND PHARMACOKINETICS (PK) RESULTS OF KN026 (A HER2 BISPECIFIC ANTIBODY) MONOTHERAPY IN ADVANCED SOLID TUMOR PATIENTS WITH HER2 EXPRESSION
Authors: Xu Ting , Lv Yuan , Sun Jie , Peng Jianjian , Li Jingqiu , Li Xionghui , Guo Baohong
Published: July 2023

Background

KN026 is a novel bispecific antibody and simultaneously binds to two distinct HER2 epitopes which are the same domains as trastuzumab (ECD4) and pertuzumab (ECD2). It showed higher maximal binding than monospecific HER2 antibodies and favors that crosslinking of HER2 receptors could enhance the receptors internalization in preclinical studies. KN026 significantly inhibited the growth of human cancer cell lines and demonstrated obviously antitumor activity against different xenografts models. The encouraging efficacy and manageable safety of KN026 were reported in Chinese cancer patients (pts) with HER2 expression and ph3 study is ongoing in gastric cancer (NCT05427383).

Methods

The late line solid tumor pts with HER2 expression who were refractory to or ineligible for standard therapy were recruited in this phase I dose-escalation study in US (NCT03847168). All pts intravenously received KN026 monotherapy at ascending dose of 10 mg/kg (QW), 20 mg/kg (Q2W) or 30 mg/kg (Q3W). Dose escalation followed standard “3 + 3” design. Expansion was determined by Safety Monitoring Committee (SMC). The primary objectives were to evaluate safety and tolerability of KN026 and determine the MTD and/or RP2D. Safety was evaluated according to CTCAE v 5.0, and efficacy was assessed by RECIST 1.1.

Results

A total of 22 pts with median 4 lines prior treatment were enrolled, including 5 breast cancer pts, 3 gastric or gastroesophageal junction cancer pts and 14 other solid tumor pts. 21 pts were included in the efficacy analysis. The median age was 57.0 (47-79), with 8 males and 14 females and most of pts were Caucasian (72.7%). 3, 10 (7 at expansion phase), and 9 (6 at expansion phase) pts were treated at 10mg/kg, 20mg/kg, 30mg/kg, respectively. No dose-limiting toxicities (DLTs) were observed and MTD wasn’t reached. 20 pts (90.9%) occurred TRAEs and the common (≥20%) TRAEs were diarrhea (45.5%), fatigue (40.9%), chills (36.4%) and nausea (27.3%). Most of TRAE were Gr 1-2, and only 3 pts (13.6%) experienced ≥ Gr3 TRAE (anemia, fatigue and pneumonitis) without treatment discontinuation and death caused by KN026. 4 of 21 pts (1 at 10mg/kg, 2 at 20 mg/kg, 1 at 30mg/kg) achieved objective response (ORR 19.0%, 95% CI: 5.5, 41.9), and DCR was 61.9% (95% CI: 38.4, 81.9). The exposure of KN026 and T1/2 increased with dose escalation. Accumulation ratio of Cmax and AUC was 1.18-1.42 and 1.14-1.71. The concentration of Ctrough was over 20μM at all dose levels. There was only one positive ADA sample in 20 mg/kg group in C1D1. And the RP2D was 20mg/kg Q2W or 30mg/kg Q3W.

Conclusion

KN026 was well tolerated and showed the promising anti-tumor activity in US pts with HER2 expression. Besides, KN026 has well pharmacokinetic profile and favorable immunogenicity.
Wonderful Worlds: Disinterested Engagement and Environmental Aesthetic Appreciation
Authors: Claessens Benjamin
Published: July 2023

Among the infinitude of nature’s various forms, precisely what should we aesthetically appreciate? And supposing we come to achieve such discernment, how should we properly appreciate the aesthetic qualities we thereby find? To address these questions, Carlson has argued that the aesthetic appreciation of nature ought to be guided by scientific insight. In response, non-cognitivists have levelled criticism and suggested alternatives, yet Carlson’s (2009) scientific cognitivism remains the best-argued approach to nature appreciation in the field. One non-cognitivist position that Carlson rejects—although much too quickly—is Berleant’s (1985)engagement model. The purpose of this paper is to modify and revive that model. Specifically, I will argue that genuine engagement requires a particular form of disinterest. The result is a non-cognitivist approach to the aesthetic appreciation of nature, stronger than the extant alternatives.
Chasing the fitness optimum: temporal variation in the genetic and environmental expression of life-history traits for a perennial plant
Authors: Kulbaba Mason W , Yoko Zebadiah , Hamilton Jill A
Published: July 2023

Background and Aims

The ability of plants to track shifting fitness optima is crucial within the context of global change, where increasing environmental extremes may have dramatic consequences for life history, fitness, and ultimately population persistence. However, tracking changing conditions relies on the relationship between genetic and environmental variance, where selection may favour plasticity, the evolution of genetic differences, or both depending on the spatial and temporal scale of environmental heterogeneity.

Methods

Over three years, we compared the genetic and environmental components of phenological and life-history variation in a common environment for the spring perennial Geum triflorum. Populations were sourced from alvar habitats that exhibit extreme but predictable annual flood–desiccation cycles and prairie habitats that exhibit similar but less predictable variation in water availability.

Key Results

Heritability was generally higher for early life-history (emergence probability) relative to later life-history traits (total seed mass), indicating that traits associated with establishment are under stronger genetic control relative to later life-history fitness expressions, where plasticity may play a larger role. This pattern was particularly notable in seeds sourced from environmentally extreme but predictable alvar habitats relative to less predictable prairie environments. Fitness landscapes based on seed source origin, largely characterized by varying water availability and flower production, described selection as the degree of maladaptation of seed source environment relative to the prairie common garden environment. Plants from alvar populations were consistently closer to the fitness optimum across all years. Annually, the breadth of the fitness optimum expanded primarily along a moisture gradient, with inclusion of more populations onto the expanding optimum.

Conclusions

These results highlight the importance of temporally and spatially varying selection in life-history evolution, indicating plasticity may become a primary mechanism needed to track fitness for later life-history events within perennial systems.
Hydrolysis-transglycosylation of sucrose and production of β-(2→1)-fructan by inulosucrase from Neobacillus drentensis 57N
Authors: Kido Yusuke , Saburi Wataru , Nagura Taizo , Mori Haruhide
Published: July 2023

Inulin, β-(2→1)-fructan, is a beneficial polysaccharide used as a functional food ingredient. Microbial inulosucrases (ISs), catalyzing β-(2→1)-transfructosylation, produce β-(2→1)-fructan from sucrose. In this study, we identified a new IS (NdIS) from the soil isolate, Neobacillus drentensis 57N. Sequence analysis revealed that, like other Bacillaceae ISs, NdIS consists of a glycoside hydrolase family 68 domain and shares most of the 1-kestose-binding residues of the archaeal IS, InuHj. Native and recombinant NdIS were characterized. NdIS is a homotetramer. It does not require calcium for activity. High performance liquid chromatography and 13C-nuclear magnetic resonance indicated that NdIS catalyzed the hydrolysis and β-(2→1)-transfructosylation of sucrose to synthesize β-(2→1)-fructan with chain lengths of 42 or more residues. The rate dependence on sucrose concentration followed hydrolysis–transglycosylation kinetics, and a 50% transglycosylation ratio was obtained at 344 m m sucrose. These results suggest that transfructosylation from sucrose to β-(2→1)-fructan occurs predominantly to elongate the fructan chain because sucrose is an unfavorable acceptor.
An integrative latent class model of heterogeneous data modalities for diagnosing kidney obstruction
Authors: Jang Jeong Hoon , Chang Changgee , Manatunga Amita K , Taylor Andrew T , Long Qi
Published: July 2023

Radionuclide imaging plays a critical role in the diagnosis and management of kidney obstruction. However, most practicing radiologists in US hospitals have insufficient time and resources to acquire training and experience needed to interpret radionuclide images, leading to increased diagnostic errors. To tackle this problem, Emory University embarked on a study that aims to develop a computer-assisted diagnostic (CAD) tool for kidney obstruction by mining and analyzing patient data comprised of renogram curves, ordinal expert ratings on the obstruction status, pharmacokinetic variables, and demographic information. The major challenges here are the heterogeneity in data modes and the lack of gold standard for determining kidney obstruction. In this article, we develop a statistically principled CAD tool based on an integrative latent class model that leverages heterogeneous data modalities available for each patient to provide accurate prediction of kidney obstruction. Our integrative model consists of three sub-models (multilevel functional latent factor regression model, probit scalar-on-function regression model, and Gaussian mixture model), each of which is tailored to the specific data mode and depends on the unknown obstruction status (latent class). An efficient MCMC algorithm is developed to train the model and predict kidney obstruction with associated uncertainty. Extensive simulations are conducted to evaluate the performance of the proposed method. An application to an Emory renal study demonstrates the usefulness of our model as a CAD tool for kidney obstruction.
Neural substrate underlying the learning of a passage with unfamiliar vocabulary and syntax
Authors: Wang Jing , Wang Xiaosha , Zou Jiajie , Duan Jipeng , Shen Zhuowen , Xu Nannan , Chen Yan , Zhang Jianfeng , He Hongjian , Bi Yanchao , Ding Nai
Published: July 2023

Speech comprehension is a complex process involving multiple stages, such as decoding of phonetic units, recognizing words, and understanding sentences and passages. In this study, we identify cortical networks beyond basic phonetic processing using a novel passage learning paradigm. Participants learn to comprehend a story composed of syllables of their native language, but containing unfamiliar vocabulary and syntax. Three learning methods are employed, each resulting in some degree of learning within a 12-min learning session. Functional magnetic resonance imaging results reveal that, when listening to the same story, the classic temporal-frontal language network is significantly enhanced by learning. Critically, activation of the left anterior and posterior temporal lobe correlates with the learning outcome that is assessed behaviorally through, e.g. word recognition and passage comprehension tests. This study demonstrates that a brief learning session is sufficient to induce neural plasticity in the left temporal lobe, which underlies the transformation from phonetic units to the units of meaning, such as words and sentences.
Mapping between cognitive theories and psycho-physiological models of attention system performance
Authors: Guidetti Oliver A , Speelman Craig P , Bouhlas Peter
Published: July 2023

Declines in the capacity to sustain attention to repetitive, monotonous tasks is a phenomenon known as vigilance decrement (Endsley M, Kiris E. The out-of-the-loop performance problem and level of control in automation. 1995. Hum Factors. 37:32–64). This review compares cognitive theories with psycho-physiological models of vigilance decrement, and a gap is identified in mapping between the 2. That is, theories of vigilance decrement refer to “cognitive” resources; by contrast, psychophysiological models of the cerebral systems associated with attention explain performance functions according to neurochemical resources. A map does not currently exist in the literature that bridges the gap between cognitive theories of vigilance decrement and psychophysiological models of the human attention system. The link between “cognitive resource” theories of vigilance decrement and the psychophysiological models of attention performance is a gap in the literature that this review fills. This comprehensive review provides an expanded psychophysiological understanding of vigilance decrement that could help inform the management of declines in sustained attention capacity in operational settings. In addition, elucidating the link between cognitive theories of vigilance decrement and psychophysiological models of the human attention system might be used to treat and better understand pathologies such as attention-deficit hyperactivity disorder.
Mass Tuberculosis Screening Among the Elderly: A Population-Based Study in a Well-Confined, Rural County in Eastern China
Authors: Hu Zhengfang , Liu Kui , Zhou Meng , Jiang Xineng , Feng Yaling , Yu Zhicheng , Li Yuhao , Chen Songhua , Wu Qian , Wang Wei , Horsburgh C Robert , Zhang Yu , Zhou Lin , Chen Bin , Hu Chonggao , Martinez Leonardo
Published: July 2023

Background

Mass tuberculosis (TB) screening has been recommended in certain high-risk populations. However, population-based screening interventions have rarely been implemented. Whether mass screening improves health equity is unknown.

Methods

We implemented a mass TB screening intervention among elderly persons (>60 years old) in Lanxi County, China. Standardized questionnaires, physical examinations, and chest radiographs (CXRs) were administered to all participants. Systematic testing with computed tomography, smear, culture, or Xpert was performed among persons with an abnormal CXR. We assessed TB prevalence per 100 000 persons and constructed multivariable regression models among subgroups that were and were not screened. Medical insurance was categorized as participation in either a basic program with limited coverage or a more comprehensive coverage program.

Results

In total, 49 339 individuals (32% of the elderly population in Lanxi) participated in the screening. One hundred fifteen screened persons were diagnosed with TB (233 cases per 100 000 persons), significantly higher than persons not screened (168 cases among 103 979 person-years; prevalence-to-case notification ratio, 1.44 [95% confidence interval {CI}, 1.14–1.83]). This increase was largely driven by diagnosis of asymptomatic disease during mass screening (n = 57 [50% of participants with TB]). Participants with basic medical insurance were much more likely to be diagnosed through mass screening than by passive detection (adjusted odds ratio, 4.52 [95% CI, 1.35–21.28]).

Conclusions

In a population-based, mass TB screening intervention encompassing >30% of the elderly population in a county in rural China, case finding was 44% higher than background detection, driven by diagnosis of TB without recognized symptoms. Importantly, mass screening identified TB in people with limited healthcare options who were less likely to be found through background case detection.
Bringing freedom back to developmentalism: industrialisation as national independence
Authors: Ahumada José Miguel
Published: July 2023

Why is developmentalism as an economic school aimed at the industrialisation of peripheral nations? Based on a reading of key authors from both the ‘American System of political economy’ of the 19th century and the Latin American structuralist and dependency schools of the 20th century, this article suggests that the answer lies, not in an economic, but in a political dimension: to ensure the material basis for national freedom. To sustain this hypothesis, the article argues that there is a common implicit conception of freedom shared by Alexander Hamilton, Henry Carey and Friedrich List, on the side of the American school, and Fernando Henrique Cardoso, Raúl Prebisch, Celso Furtado and Osvaldo Sunkel, from the Latin American school. This conception is heir to the idea of Machiavelli’s Free State, its core is the notion of liberty as non-dependency and collective autonomy and identifies in industrialisation the way for a periphery to be able to live without depending on the arbitrary will of foreign powers. This definition differs from both the liberal and capability conceptions of freedom and allows for the identification of forms of domination that occur between nations and through the global market that requires the peripheries to erect autonomous collective productive capabilities for their overcoming.
Cardiovascular outcomes in breast cancer survivors: a systematic review and meta-analysis
Authors: Galimzhanov Akhmetzhan , Istanbuly Sedralmontaha , Tun Han Naung , Ozbay Benay , Alasnag Mirvat , Ky Bonnie , Lyon Alexander R , Kayikcioglu Meral , Tenekecioglu Erhan , Panagioti Maria , Kontopantelis Evangelos , Abdel-Qadir Husam , Mamas Mamas A
Published: July 2023

Aims

It is unclear whether the future risk of cardiovascular events in breast cancer (Bc) survivors is greater than in the general population. This meta-analysis quantifies the risk of cardiovascular disease development in Bc patients, compared to the risk in a general matched cancer-free population, and reports the incidence of cardiovascular events in patients with Bc.

Methods and results

We searched PubMed, Scopus, and Web of Science databases (up to 23 March 2022) for observational studies and post hoc analyses of randomized controlled trials. Cardiovascular death, heart failure (HF), atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), and stroke were the individual endpoints for our meta-analysis. We pooled incidence rates (IRs) and risk in hazard ratios (HRs), using random-effects meta-analyses. Heterogeneity was reported through the I2 statistic, and publication bias was examined using funnel plots and Egger’s test in the meta-analysis of risk. One hundred and forty-two studies were identified in total, 26 (836 301 patients) relevant to the relative risk and 116 (2 111 882 patients) relevant to IRs. Compared to matched cancer-free controls, Bc patients had higher risk for cardiovascular death within 5 years of cancer diagnosis [HR = 1.09; 95% confidence interval (CI): 1.07, 1.11], HF within 10 years (HR = 1.21; 95% CI: 1.1, 1.33), and AF within 3 years (HR = 1.13; 95% CI: 1.05, 1.21). The pooled IR for cardiovascular death was 1.73 (95% CI 1.18, 2.53), 4.44 (95% CI 3.33, 5.92) for HF, 4.29 (95% CI 3.09, 5.94) for CAD, 1.98 (95% CI 1.24, 3.16) for MI, 4.33 (95% CI 2.97, 6.30) for stroke of any type, and 2.64 (95% CI 2.97, 6.30) for ischaemic stroke.

Conclusion

Breast cancer exposure was associated with the increased risk for cardiovascular death, HF, and AF. The pooled incidence for cardiovascular endpoints varied depending on population characteristics and endpoint studied.

Registration

CRD42022298741.
Glyoxal as an alternative fixative for single-cell RNA sequencing
Authors: Bageritz Josephine , Krausse Niklas , Yousefian Schayan , Leible Svenja , Valentini Erica , Boutros Michael
Published: July 2023

Single-cell RNA sequencing has become an important method to identify cell types, delineate the trajectories of cell differentiation in whole organisms, and understand the heterogeneity in cellular responses. Nevertheless, sample collection and processing remain a severe bottleneck for single-cell RNA sequencing experiments. Cell isolation protocols often lead to significant changes in the transcriptomes of cells, requiring novel methods to preserve cell states. Here, we developed and benchmarked protocols using glyoxal as a fixative for single-cell RNA sequencing applications. Using Drop-seq methodology, we detected a large number of transcripts and genes from glyoxal-fixed Drosophila cells after single-cell RNA sequencing. The effective glyoxal fixation of transcriptomes in Drosophila and human cells was further supported by a high correlation of gene expression data between glyoxal-fixed and unfixed samples. Accordingly, we also found highly expressed genes overlapping to a large extent between experimental conditions. These results indicated that our fixation protocol did not induce considerable changes in gene expression and conserved the transcriptome for subsequent single-cell isolation procedures. In conclusion, we present glyoxal as a suitable fixative for Drosophila cells and potentially cells of other species that allow high-quality single-cell RNA sequencing applications.
FREQ-Seq2: a method for precise high-throughput combinatorial quantification of allele frequencies
Authors: Zhao Roy , Lukacsovich Tamas , Gaut Rebecca , Emerson J J
Published: July 2023

The accurate determination of allele frequencies is crucially important across a wide range of problems in genetics, such as developing population genetic models, making inferences from genome-wide association studies, determining genetic risk for diseases, as well as other scientific and medical applications. Furthermore, understanding how allele frequencies change over time in populations is central to ascertaining their evolutionary dynamics. We present a precise, efficient, and economical method (FREQ-Seq2) for quantifying the relative frequencies of different alleles at loci of interest in mixed population samples. Through the creative use of paired barcode sequences, we exponentially increased the throughput of the original FREQ-Seq method from 48 to 2,304 samples. FREQ-Seq2 can be targeted to specific genomic regions of interest, which are amplified using universal barcoded adapters to generate Illumina sequencing libraries. Our enhanced method, available as a kit along with open-source software for analyzing sequenced libraries, enables the detection and removal of errors that are undetectable in the original FREQ-Seq method as well as other conventional methods for allele frequency quantification. Finally, we validated the performance of our sequencing-based approach with a highly multiplexed set of control samples as well as a competitive evolution experiment in Escherichia coli and compare the latter to estimates derived from manual colony counting. Our analyses demonstrate that FREQ-Seq2 is flexible, inexpensive, and produces large amounts of data with low error, low noise, and desirable statistical properties. In summary, FREQ-Seq2 is a powerful method for quantifying allele frequency that provides a versatile approach for profiling mixed populations.
A simulation study comparing advanced marker-assisted selection with genomic selection in tree breeding programs
Authors: Degen Bernd , Müller Niels A
Published: July 2023

Advances in DNA sequencing technologies allow the sequencing of whole genomes of thousands of individuals and provide several million single nucleotide polymorphisms (SNPs) per individual. These data combined with precise and high-throughput phenotyping enable genome-wide association studies (GWAS) and the identification of SNPs underlying traits with complex genetic architectures. The identified causal SNPs and estimated allelic effects could then be used for advanced marker-assisted selection (MAS) in breeding programs. But could such MAS compete with the broadly used genomic selection (GS)? This question is of particular interest for the lengthy tree breeding strategies. Here, with our new software “SNPscan breeder,” we simulated a simple tree breeding program and compared the impact of different selection criteria on genetic gain and inbreeding. Further, we assessed different genetic architectures and different levels of kinship among individuals of the breeding population. Interestingly, apart from progeny testing, GS using gBLUP performed best under almost all simulated scenarios. MAS based on GWAS results outperformed GS only if the allelic effects were estimated in large populations (ca. 10,000 individuals) of unrelated individuals. Notably, GWAS using 3,000 extreme phenotypes performed as good as the use of 10,000 phenotypes. GS increased inbreeding and thus reduced genetic diversity more strongly compared to progeny testing and GWAS-based selection. We discuss the practical implications for tree breeding programs. In conclusion, our analyses further support the potential of GS for forest tree breeding and improvement, although MAS may gain relevance with decreasing sequencing costs in the future.
Long-Term PM2.5 Exposure, Lung Function, and Cognitive Function Among Middle-Aged and Older Adults in China
Authors: Ye Zirong , Li Xueru , Lang Haoxiang , Fang Ya
Published: July 2023

Background

Long-term exposure to PM2.5 is related to poor lung function and cognitive impairment, but less is known about the pathway involved in this association. We aimed to explore whether the effect of PM2.5 on cognitive function was mediated by lung function.

Methods

A total of 7 915 adults older than 45 years old were derived from the China Health and Retirement Longitudinal Study (CHARLS) collected in 2011 and 2015. PM2.5 exposure was estimated using a geographically weighted regression model. Lung function was measured by peak expiratory flow (PEF). Cognitive function was evaluated through a structured questionnaire with 4 dimensions: episodic memory, attention, orientation, and visuoconstruction. Under the counterfactual framework, causal mediation analysis was applied to examine direct and indirect associations.

Results

An interquartile range (IQR) increase in PM2.5 change was significantly related to an 8.480 (95% confidence interval [CI]: 3.116, 13.845) decrease in PEF change and a 0.301 (95% CI: 0.100, 0.575) decrease in global cognitive score change. The direct and indirect effects of PM2.5 exposure on global cognitive performance were −0.279 (95% CI: −0.551, −0.060) and −0.023 (95% CI: −0.041, −0.010), respectively. The proportion of the indirect effect was 7.48% (p = .010). The same significant association appeared in only 2 dimensions, episodic memory and attention, which were both mediated by PEF.

Conclusions

Lung function played a partially mediating role in the association between long-term PM2.5 exposure and cognition. More clean air actions should be undertaken to improve lung function and cognitive function in older adults.
Determinants of initiation, continuation and cessation of smokeless tobacco use among pregnant and lactating women: a qualitative study from low-income communities in urban India
Authors: Singh Shalini , Jain Rupal , Joshi Isha , Chandra Rishita , Singh Lucky , Singh Prashant Kumar
Published: July 2023

Smokeless tobacco (SLT) consumption increases the risk of cardiovascular diseases and cancer and leads to adverse reproductive health outcomes among women and newborns. This study examines the factors associated with initiation, continuation and cessation of SLT use among women in the reproductive age so as to formulate and include prevention and cessation interventions from its inception. The study was conducted in urban low-income communities in India. Using snowball and purposive sampling techniques, in-depth interviews were conducted with 20 pregnant and 22 lactating women who currently used SLT products. Data were analysed using thematic analysis with the help of QSR NVivo software. Findings revealed that factors such as people influencing usage change with different life stages including pre-marital and post-marital periods. Perceived health benefits, altered taste preferences during pregnancy and social influences were also studied. Women were found to be more aware of the harmful effects of tobacco during pregnancy than during breastfeeding. Social stigma around women consuming tobacco acted as a major driving factor for cessation. Most of the participants were willing to quit but were not aware of any technique or programme for cessation. The findings of the study highlight the need to develop behavioural change intervention tools, which are culturally and locally appropriate and have a gender-sensitive approach. Different socio-cultural factors associated with initiation/cessation at different life stages should also be taken into consideration while developing these tools.
Socioeconomic inequalities in COVID-19 incidence during the first six waves in Barcelona
Authors: Martinez-Beneito Miguel Angel , Marí-Dell’Olmo Marc , Sánchez-Valdivia Nacho , Rodríguez-Sanz Maica , Pérez Glòria , Pasarín Maria Isabel , Rius Cristina , Artazcoz Lucía , Prieto Raquel , Pérez Katherine , Borrell Carme
Published: July 2023

Background

The emergence of SARS-CoV-2 affected urban areas. In Barcelona, six waves of COVID-19 hit the city between March 2020 and March 2022. Inequalities in the incidence of COVID-19 have been described. However, no studies have examined the daily trends of socioeconomic inequalities and how they changed during the different phases of the pandemic. The aim of this study is to analyse the dynamic socioeconomic inequalities in the incidence of COVID-19 during the six waves in Barcelona.

Methods

We examined the proportion of daily cases observed in the census tracts in the lower income tercile compared with the proportion of daily cases observed in the sum of the lower and higher income terciles. Daily differences in these proportions were assessed as a function of the epidemic waves, sex, age group, daily incidence and daily change in the incidence. A logistic regression model with an autoregressive term was used for statistical analysis.

Results

A time-dynamic effect was found for socioeconomic inequalities in the incidence of COVID-19. In fact, belonging to a lower-income area changed from being a risk factor (Waves 1, 2, 4 and 5) to being a protective factor in the sixth wave of the pandemic. Age also had a significant effect on incidence, which also changed over the different waves of the pandemic. Finally, the lower-income areas showed a comparatively lower incidence during the ascending phase of the epidemic waves.

Conclusion

Socioeconomic inequalities in COVID-19 changed by wave, age group and wave phase.
On Triple Product L-Functions and a Conjecture of Harris–Venkatesh
Authors: Lecouturier Emmanuel
Published: July 2023

Harris and Venkatesh made a conjecture relating the derived Hecke operators and the adjoint motivic cohomology in the setting of weight one modular forms. This conjecture was proved under some conditions in the dihedral case by Darmon–Harris–Rotger–Venkatesh. We use a new approach to prove more general cases of the conjecture (up to sign). Our approach relies on Waldspurger’s formula for the central value of Rankin L-series and Ichino’s formula for the triple product L-function.
Polynomial Volume Growth of Quasi-Unipotent Automorphisms of Abelian Varieties (with an Appendix in Collaboration with Chen Jiang)
Authors: Hu Fei
Published: July 2023

Let $X$ be an abelian variety over an algebraically closed field $\textbf{k}$ and $f$ a quasi-unipotent automorphism of $X$. When $\textbf{k}$ is the field of complex numbers, Lin, Oguiso, and D.-Q. Zhang provide an explicit formula for the polynomial volume growth of (or equivalently, for the Gelfand–Kirillov dimension of the twisted homogeneous coordinate ring associated with) the pair $(X, f)$, by an analytic argument. We give an algebraic proof of this formula that works in arbitrary characteristic. In the course of the proof, we obtain the following: (1) a new description of the action of endomorphisms on the $\ell $-adic Tate spaces, in comparison with recent results of Zarhin and Poonen–Rybakov; (2) a partial converse to a result of Reichstein, Rogalski, and J.J. Zhang on quasi-unipotency of endomorphisms and their pullback action on the rational Néron–Severi space $\textsf{N}^{1}(X)_{\textbf{Q}}$ of $\textbf{Q}$-divisors modulo numerical equivalence; and (3) the maximum size of Jordan blocks of (the Jordan canonical form of) $f^{*}|_{\textsf{N}^{1}(X)_{\textbf{Q}}}$ in terms of the action of $f$ on the Tate space $V_{\ell }(X)$.
Conductor-Discriminant Inequality for Hyperelliptic Curves in Odd Residue Characteristic
Authors: Obus Andrew , Srinivasan Padmavathi
Published: July 2023

We prove an inequality between the conductor and the discriminant for all hyperelliptic curves defined over discretely valued fields $K$ with perfect residue field of characteristic not $2$. Specifically, if such a curve is given by $y^{2} = f(x)$ with $f(x) \in \mathcal{O}_{K}[x]$, and if $\mathcal{X}$ is its minimal regular model over $\mathcal{O}_{K}$, then the negative of the Artin conductor of $\mathcal{X}$ (and thus also the number of irreducible components of the special fiber of $\mathcal{X}$) is bounded above by the valuation of $\operatorname{disc}(f)$. There are no restrictions on genus of the curve or on the ramification of the splitting field of $f$. This generalizes earlier work of Ogg, Saito, Liu, and the second author.
Effect of the L74I Polymorphism on Fitness of Cabotegravir-Resistant Variants of Human Immunodeficiency Virus 1 Subtype A6
Authors: Hu Zixin , Cordwell Trevor , Nguyen Hieu , Li Jialin , Jeffrey Jerry L , Kuritzkes Daniel R
Published: July 2023

The presence of human immunodeficiency virus (HIV) 1 subtype A6, characterized by the L74I integrase (IN) polymorphism, is associated with confirmed virologic failure in clinical trials of long-acting cabotegravir and rilpivirine. We investigated the effect of L74I on replication capacity (RC) of recombinant viruses carrying this polymorphism in combination with various IN stand-transfer inhibitor resistance mutations. The presence of L74I conferred greater RC to recombinant viruses expressing HIV-1 A6 IN when present together with G118R, G140R, Q148H, and R263K; no significant difference in RC was observed for the Q148K or R mutants. These findings may explain, in part, the association of HIV-1 subtype A6 with virologic failure.
Discussion of the 2022 Hansen Lecture: “The Evolution of the Use of Models in Survey Sampling”
Authors: Breidt F Jay
Published: July 2023

The 2022 Hansen Lecture gave a broad overview of the use of models in survey sampling, with emphasis on modeling approaches to incorporating auxiliary information in survey estimators. This discussion expands upon some issues in model-assisted estimation, exploring data needs and the availability of multipurpose weights for advanced modeling methods.
Roles of auxin pathways in maize biology
Authors: Cowling Craig L , Dash Linkan , Kelley Dior R
Published: July 2023

Phytohormones play a central role in plant development and environmental responses. Auxin is a classical hormone that is required for organ formation, tissue patterning, and defense responses. Auxin pathways have been extensively studied across numerous land plant lineages, including bryophytes and eudicots. In contrast, our understanding of the roles of auxin in maize morphogenesis and immune responses is limited. Here, we review evidence for auxin-mediated processes in maize and describe promising areas for future research in the auxin field. Several recent transcriptomic and genetic studies have demonstrated that auxin is a key influencer of both vegetative and reproductive development in maize (namely roots, leaves, and kernels). Auxin signaling has been implicated in both maize shoot architecture and immune responses through genetic and molecular analyses of the conserved co-repressor RAMOSA ENHANCER LOCUS2. Polar auxin transport is linked to maize drought responses, root growth, shoot formation, and leaf morphogenesis. Notably, maize has been a key system for delineating auxin biosynthetic pathways and offers many opportunities for future investigations on auxin metabolism. In addition, crosstalk between auxin and other phytohormones has been uncovered through gene expression studies and is important for leaf and root development in maize. Collectively these studies point to auxin as a cornerstone for maize biology that could be leveraged for improved crop resilience and yield.
Chromosome-Aware Phylogenomics of Assassin Bugs (Hemiptera: Reduvioidea) Elucidates Ancient Gene Conflict
Authors: Knyshov Alexander , Gordon Eric R L , Masonick Paul K , Castillo Stephanie , Forero Dimitri , Hoey-Chamberlain Rochelle , Hwang Wei Song , Johnson Kevin P , Lemmon Alan R , Moriarty Lemmon Emily , Standring Samantha , Zhang Junxia , Weirauch Christiane
Published: July 2023

Though the phylogenetic signal of loci on sex chromosomes can differ from those on autosomes, chromosomal-level genome assemblies for nonvertebrates are still relatively scarce and conservation of chromosomal gene content across deep phylogenetic scales has therefore remained largely unexplored. We here assemble a uniquely large and diverse set of samples (17 anchored hybrid enrichment, 24 RNA-seq, and 70 whole-genome sequencing samples of variable depth) for the medically important assassin bugs (Reduvioidea). We assess the performance of genes based on multiple features (e.g., nucleotide vs. amino acid, nuclear vs. mitochondrial, and autosomal vs. X chromosomal) and employ different methods (concatenation and coalescence analyses) to reconstruct the unresolved phylogeny of this diverse (∼7,000 spp.) and old (>180 Ma) group. Our results show that genes on the X chromosome are more likely to have discordant phylogenies than those on autosomes. We find that the X chromosome conflict is driven by high gene substitution rates that impact the accuracy of phylogenetic inference. However, gene tree clustering showed strong conflict even after discounting variable third codon positions. Alternative topologies were not particularly enriched for sex chromosome loci, but spread across the genome. We conclude that binning genes to autosomal or sex chromosomes may result in a more accurate picture of the complex evolutionary history of a clade.
Takayasu’s arteritis after a prolonged course of hypertrophic osteoarthropathy
Authors: Jubashi Takashi , Horai Yoshiro , Tomokawa Takuya , Hara Kazusato , Kawakami Atsushi
Published: July 2023

A 71-year-old male with hypertrophic osteoarthropathy was referred to our hospital because of a nocturnal fever and tenderness stretching from the left parotid region to the left front neck, in which antibacterials were ineffective. He was diagnosed with Takayasu’s arteritis following findings of contrast-enhanced computed tomography and neck ultrasound. This is the first report to describe the development of Takayasu’s arteritis after a prolonged course of typical hypertrophic osteoarthropathy, and the proposed hypertrophic osteoarthropathy and Takayasu’s arteritis have common underlying pathophysiological factors.
Interactions between chromium species and DNA in vitro and their potential role in the toxicity of hexavalent chromium
Authors: Mezencev R , Gibbons C
Published: July 2023

Epidemiological and animal studies have supported the carcinogenicity of hexavalent chromium [Cr(VI)]; however, molecular changes responsible for the induction of cancer by Cr(VI) are not entirely understood. Numerous mechanistic studies suggested the role of oxidative stress and genotoxicity in Cr(VI)-mediated carcinogenesis; however, specific types of DNA damage have not yet been conclusively attributed to specific chromium species or other reactive byproducts generated in biological systems exposed to Cr(VI). Due to the remarkably complex chemistry and biological effects of chromium species generated through the intracellular reduction of Cr(VI), their relevance for Cr(VI)-mediated carcinogenesis has not yet been fully elucidated and continues to be a subject of ongoing discussions in the field. In this report, we describe a complex world of chromium species and their reactivity with DNA and other biologically relevant molecules in vitro to inform a more complete understanding of Cr(VI)-mediated toxicity. In addition, we discuss previous results in the context of in vitro models and analytical methods to reconcile some conflicting findings on the biological role of chromium species.
Single-cell reference mapping to construct and extend cell-type hierarchies
Authors: Michielsen Lieke , Lotfollahi Mohammad , Strobl Daniel , Sikkema Lisa , Reinders Marcel J T , Theis Fabian J , Mahfouz Ahmed
Published: July 2023

Single-cell genomics is now producing an ever-increasing amount of datasets that, when integrated, could provide large-scale reference atlases of tissue in health and disease. Such large-scale atlases increase the scale and generalizability of analyses and enable combining knowledge generated by individual studies. Specifically, individual studies often differ regarding cell annotation terminology and depth, with different groups specializing in different cell type compartments, often using distinct terminology. Understanding how these distinct sets of annotations are related and complement each other would mark a major step towards a consensus-based cell-type annotation reflecting the latest knowledge in the field. Whereas recent computational techniques, referred to as ‘reference mapping’ methods, facilitate the usage and expansion of existing reference atlases by mapping new datasets (i.e. queries) onto an atlas; a systematic approach towards harmonizing dataset-specific cell-type terminology and annotation depth is still lacking. Here, we present ‘treeArches’, a framework to automatically build and extend reference atlases while enriching them with an updatable hierarchy of cell-type annotations across different datasets. We demonstrate various use cases for treeArches, from automatically resolving relations between reference and query cell types to identifying unseen cell types absent in the reference, such as disease-associated cell states. We envision treeArches enabling data-driven construction of consensus atlas-level cell-type hierarchies and facilitating efficient usage of reference atlases.
Mortality of Patients With Candidemia and COVID-19: A Systematic Review With Meta-analysis
Authors: Colaneri Marta , Giusti Emanuele Maria , Genovese Camilla , Galli Lucia , Lombardi Andrea , Gori Andrea
Published: July 2023

Mortality of candidemia in coronavirus disease 2019 (COVID-19) patients has not been deeply studied despite evidence suggesting an increased occurrence. We performed a systematic review and meta-analysis to summarize the available evidence about these patients’ mortality and length of stay. Data about the in-hospital, all-cause and 30-day mortality, and length of stay were pooled. Subgroup analyses were performed to assess sources of heterogeneity. Twenty-six articles out of the 1915 records retrieved during the search were included in this review. The pooled in-hospital mortality was 62.62% (95% CI, 54.77% to 69.86%), while the mortality in intensive care unit (ICU) was 66.77% (95% CI, 57.70% to 74.75%). The pooled median in-hospital length of stay was 30.41 (95% CI, 12.28 to 48.55) days, while the pooled median length of stay in the ICU was 28.28 (95% CI, 20.84 to 35.73) days. The subgroup analyses did not identify the sources of heterogeneity in any of the analyses. Our results showed high mortality in patients with candidemia and COVID-19, suggesting the need to consider screening measures to prevent this life-threatening condition.
Failure and Success in Agency
Authors: Heering David
Published: July 2023

Agency often consists in performing actions and engaging in activities that are successful. We pour glasses, catch objects, carry things, recite poems, and play instruments. It has therefore seemed tempting in recent philosophical thinking to conceptualise the relationship between our agentive abilities and our successes as follows: (Success) S is exercising their ability to ϕ only if S successfully ϕ-s. This paper argues that (Success) is false based on the observation that agency also often consists in making mistakes. We bungle things. We spill water, we miss objects thrown at us, we drop things, misremember lines, and mess up songs. I argue that these mistakes, doings that fall short of being a φ-ing, can only be understood as subpar exercises of the ability to φ. Since this understanding is incompatible with (Success), the thesis should be given up.
Trajectories of Informal and Formal Social Participation After Retirement
Authors: Lim-Soh Jeremy , Ang Shannon , Malhotra Rahul
Published: July 2023

Literature suggests that on average, social participation declines after retirement. However, there likely remains substantial variability in individual experiences. We rely on seven waves of the Korean Longitudinal Study of Aging to identify contrasting social participation trajectories of individuals 45 years and older after leaving work, and their individual-level correlates. Informal and formal social participation were measured through self-reported frequencies of meeting a friend and attending a group respectively. Group-based trajectory modeling delineated heterogeneous changes over time and multinomial logit regressions estimated individual-level correlates of the trajectories. While a minority of respondents experienced trajectories of decreasing social participation (6%–12%), a majority exhibited stable trajectories (79%–81%), and some even experienced increasing participation (7%–8%). There was also a U-shaped trajectory of decline and recovery in formal social participation (7%). Our findings challenge the belief that disengagement is the norm and illustrate the heterogeneous experiences of social participation after retirement. Returning to work, vs. stopping work for an extended period, was associated with favorable trajectories, pointing to the strong connection between work and social participation, and the potential for interventions that promote bridge employment and lifelong learning. Interestingly, the high stable trajectory of informal participation was associated with certain factors that may be considered vulnerabilities, such as being older, female, single, living in non-metropolitan regions, and retiring from irregular work. This highlights the possibility that despite facing challenges, older adults can aspire towards high social participation.
VThe Early Sixteenth Century
Authors: Smith Edward
Published: July 2023

This chapter has five sections: 1. General: Drama and Prose; 2. General: Verse; 3. More; 4. Skelton; 5. Wyatt

In a sign of the rude health of critical literature on earlier Tudor topics, 2021 featured a broad-spanning range of articles and chapters that focused as much, if not more, on writers and works hitherto accorded little attention as on the canonical figures of the period. A case in point is the fact that more articles on Stephen Hawes saw the light of print (three) than on Henry Howard, Earl of Surrey (none).
Complex regional pain syndrome
Authors: Mills Micayah , Howell Christopher M.
Published: July 2023

Complex regional pain syndrome (CRPS), formerly called reflex sympathetic dystrophy (RSD), is a chronic pain phenomenon associated with an alteration in peripheral and central pain perception in a localized body region. Because of the many risk factors associated with this phenomenon, the true nature of the disease risk and clinical course are a challenge to predict. After the diagnosis is confirmed and treatment is provided promptly, clinicians must consider patient health and function holistically to foster improvement in overall quality of life.