bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Relevant Time Windows in the Association Between PM2.5 Exposure and Amyotrophic Lateral Sclerosis: A Case-Control Study in Denmark
Authors: Nunez Yanelli , Balalian Arin , Parks Robbie M , He Mike Z , Hansen Johnni , Raaschou-Nielsen Ole , Ketzel Matthias , Khan Jibran , Brandt Jørge , Vermeulen Roel , Peters Susan , Weisskopf Marc G , Re Diane B , Goldsmith Jeff , Kioumourtzoglou Marianthi-Anna
Published: April 2023

Studies suggest a link between particulate matter less than or equal to 2.5 μm in diameter (PM2.5) and amyotrophic lateral sclerosis (ALS), but to our knowledge critical exposure windows have not been examined. We performed a case-control study in the Danish population spanning the years 1989–2013. Cases were selected from the Danish National Patient Registry based on International Classification of Diseases codes. Five controls were randomly selected from the Danish Civil Registry and matched to a case on vital status, age, and sex. PM2.5 concentration at residential addresses was assigned using monthly predictions from a dispersion model. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for confounding. We evaluated exposure to averaged PM2.5 concentrations 12–24 months, 2–6 years, and 2–11 years pre–ALS diagnosis; annual lagged exposures up to 11 years prediagnosis; and cumulative associations for exposure in lags 1–5 years and 1–10 years prediagnosis, allowing for varying association estimates by year. We identified 3,983 cases and 19,915 controls. Cumulative exposure to PM2.5 in the period 2–6 years prediagnosis was associated with ALS (OR = 1.06, 95% CI: 0.99, 1.13). Exposures in the second, third, and fourth years prediagnosis were individually associated with higher odds of ALS (e.g., for lag 1, OR = 1.04, 95% CI: 1.00, 1.08). Exposure to PM2.5 within 6 years before diagnosis may represent a critical exposure window for ALS.
National trends in prescription drug expenditures and projections for 2023
Authors: Tichy Eric M , Hoffman James M , Tadrous Mina , Rim Matthew H , Suda Katie J , Cuellar Sandra , Clark John S , Newell Mary Kate , Schumock Glen T
Published: April 2023

Purpose

To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2023 in the United States, with a focus on the nonfederal hospital and clinic sectors.

Methods

Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2023 were reviewed, including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, diabetes medications, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2023 were based on a combination of quantitative analyses and expert opinion.

Results

In 2022, overall pharmaceutical expenditures in the US grew 9.4% compared to 2021, for a total of $633.5 billion. Utilization (a 5.9% increase), price (a 1.7% increase) and new drugs (a 1.8% increase) drove this increase. Adalimumab was the top-selling drug in 2022, followed by semaglutide and apixaban. Drug expenditures were $37.2 billion (a 5.9% decrease) and $116.9 billion (a 10.4% increase) in nonfederal hospitals and clinics, respectively. In clinics, new products and increased utilization growth drove growth, with a small impact from price changes. In nonfederal hospitals, a drop in utilization led to a decrease in expenditures, with price changes and new drugs contributing to growth in spending. Several new drugs that will influence spending have been or are expected to be approved in 2023. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic.

Conclusion

For 2023, we expect overall prescription drug spending to rise by 6.0% to 8.0%, whereas in clinics and hospitals we anticipate increases of 8.0% to 10.0% and 1.0% to 3.0%, respectively, compared to 2022. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.
The role and mechanism of tumor necrosis factor-alpha in alcohol-induced bone loss
Authors: Wang Xiuwen , Lu Lingyun , Chen Xiang , Liang Yan , Xie Ying , Yu Xijie
Published: April 2023

Aim: It is well known that alcohol can cause bone loss and that bone mineral density has an inverse relationship with bone marrow adipocyte (BMA). However, little is known about the mechanisms that link alcohol and bone loss, and existing studies lack data on BMA in alcohol-induced bone loss. Here, wild-type (WT) and tumor necrosis factor-alpha knockout (TNF-α KO) mice were used to examine the effects of alcohol on bone metabolism. Methods: The effects of alcohol on bone metabolism were demonstrated in vivo by feeding WT and TNF-α KO mice with alcohol. The osteogenesis and adipogenesis of primary bone marrow stromal cells (BMSCs) derived from WT and TNF-α KO mice under alcohol intervention were compared in vitro. Tissue staining, cell staining, micro-CT, and quantitative RT-PCR were used to explore the potential mechanism. Results: Alcohol induced trabecular bone loss, increased BMA, and promoted the mRNA expression of Adipoq, Fabp4, visfatin， Pparg, TNF-α, IL-1β, and IL-6 in BMA in WT mice, but not in TNF-α KO mice. In addition, alcohol promoted BMSC adipogenesis and inhibited BMSC osteogenesis, while TNF-α knockout could restrain this situation. Conclusion: Our study demonstrated that alcohol may reduce bone mass by disrupting the balance of osteogenesis and adipogenesis in bone marrow, and TNF-α plays an important role in this process.
A new paradigm for addictions
Authors: Poikolainen Kari
Published: April 2023

Aim

To suggest a new paradigm for addictions.

Methods

Consideration of relevant research findings and thought experiments.

Results

Common mental motors leading to addictions are pleasure-seeking and hyperbolic discounting. The important point of the latter is that given two choices of future rewards, commonly one initially prefers the larger one available after a longer waiting time but despite this the smaller and sooner reward will be chosen when it becomes available. These are general biological properties, found at least in human beings, the rat, and the pigeon. If this continues it may create an unconscious habit, difficult to change. Several other risk factors for addictions are known, notably both externalizing and internalizing mental problems. Predisposing factors are likely to interact.

Conclusions

The above suggests a new paradigm for addictions. Pleasure provides temptations, hyperbolic discounting weakens the will. Habits emerge. Addictions seem to be a group of problems of its own kind, not diseases, because diseases do not bring about pleasure, and are not sought for pleasure.
An automatic immunofluorescence pattern classification framework for HEp-2 image based on supervised learning
Authors: Fang Kechi , Li Chuan , Wang Jing
Published: April 2023

Immunofluorescence patterns of anti-nuclear antibodies (ANAs) on human epithelial cell (HEp-2) substrates are important biomarkers for the diagnosis of autoimmune diseases. There are growing clinical requirements for an automatic readout and classification of ANA immunofluorescence patterns for HEp-2 images following the taxonomy recommended by the International Consensus on Antinuclear Antibody Patterns (ICAP). In this study, a comprehensive collection of HEp-2 specimen images covering a broad range of ANA patterns was established and manually annotated by experienced laboratory experts. By utilizing a supervised learning methodology, an automatic immunofluorescence pattern classification framework for HEp-2 specimen images was developed. The framework consists of a module for HEp-2 cell detection and cell-level feature extraction, followed by an image-level classifier that is capable of recognizing all 14 classes of ANA immunofluorescence patterns as recommended by ICAP. Performance analysis indicated an accuracy of 92.05% on the validation dataset and 87% on an independent test dataset, which has surpassed the performance of human examiners on the same test dataset. The proposed framework is expected to contribute to the automatic ANA pattern recognition in clinical laboratories to facilitate efficient and precise diagnosis of autoimmune diseases.
epiTCR: a highly sensitive predictor for TCR–peptide binding
Authors: Pham My-Diem Nguyen , Nguyen Thanh-Nhan , Tran Le Son , Nguyen Que-Tran Bui , Nguyen Thien-Phuc Hoang , Pham Thi Mong Quynh , Nguyen Hoai-Nghia , Giang Hoa , Phan Minh-Duy , Nguyen Vy
Published: April 2023

Motivation

Predicting the binding between T-cell receptor (TCR) and peptide presented by human leucocyte antigen molecule is a highly challenging task and a key bottleneck in the development of immunotherapy. Existing prediction tools, despite exhibiting good performance on the datasets they were built with, suffer from low true positive rates when used to predict epitopes capable of eliciting T-cell responses in patients. Therefore, an improved tool for TCR–peptide prediction built upon a large dataset combining existing publicly available data is still needed.

Results

We collected data from five public databases (IEDB, TBAdb, VDJdb, McPAS-TCR, and 10X) to form a dataset of >3 million TCR–peptide pairs, 3.27% of which were binding interactions. We proposed epiTCR, a Random Forest-based method dedicated to predicting the TCR–peptide interactions. epiTCR used simple input of TCR CDR3β sequences and antigen sequences, which are encoded by flattened BLOSUM62. epiTCR performed with area under the curve (0.98) and higher sensitivity (0.94) than other existing tools (NetTCR, Imrex, ATM-TCR, and pMTnet), while maintaining comparable prediction specificity (0.9). We identified seven epitopes that contributed to 98.67% of false positives predicted by epiTCR and exerted similar effects on other tools. We also demonstrated a considerable influence of peptide sequences on prediction, highlighting the need for more diverse peptides in a more balanced dataset. In conclusion, epiTCR is among the most well-performing tools, thanks to the use of combined data from public sources and its use will contribute to the quest in identifying neoantigens for precision cancer immunotherapy.

Availability and implementation

epiTCR is available on GitHub (https://github.com/ddiem-ri-4D/epiTCR).
Food security in high mountains of Central Asia: A broader perspective
Authors: Sidle Roy C , Khan Aziz Ali , Caiserman Arnaud , Qadamov Aslam , Khojazoda Zulfiqor
Published: April 2023

Addressing food security in high mountains is a multidimensional conundrum because of complex climate patterns and environmental attributes. These conditions affect water supplies, biodiversity, droughts, and other hazards. The climate change–land degradation nexus, although it is difficult to disentangle, poses formidable challenges. Isolated mountain villages, coupled with poverty, a strained subsistence existence, conflict, and marginal lands make the residents vulnerable to malnutrition, stunting, and food access. Because the arable land is mostly in confined valleys, food production is insufficient. The soils are typically infertile, with little organic matter; on hillslopes, thin soil and rock cover, coupled with short growing seasons, restrict crop production. High-elevation pastures are overgrazed, and the natural hazard impacts on food security are often overlooked. We examine food security through these multifaceted stressors, instead of merely focusing on production and distribution, and present an integrated approach to assess natural and anthropogenic stressors and feedback loops affecting food security linked to planning, mitigation, and coping strategies.
Antibiotic Use Without a Prescription: A Multisite Survey of Patient, Health System, and Encounter Characteristics
Authors: Grigoryan Larissa , Paasche-Orlow Michael K , Alquicira Osvaldo , Laytner Lindsey , Schlueter Matthew , Street Richard L , Salinas Juanita , Barning Kenneth , Mahmood Hammad , Porter Thomas W , Khan Fareed , Raphael Jean L , Faustinella Fabrizia , Trautner Barbara W
Published: April 2023

Background

Using antibiotics without a prescription is potentially unsafe and may increase the risk of antimicrobial resistance. We evaluated the effect of patient, health system, and clinical encounter factors on intention to use antibiotics without a prescription that were (1) purchased in the United States, (2) obtained from friends or relatives, (3) purchased abroad, or (4) from any of these sources.

Methods

The survey was performed January 2020–June 2021 in 6 publicly funded primary care clinics and 2 private emergency departments in Texas, United States. Participants included adult patients visiting 1 of the clinical settings. Nonprescription use was defined as use of antibiotics without a prescription; intended use was professed intention for future nonprescription antibiotic use.

Results

Of 564 survey respondents (33% Black and 47% Hispanic or Latino), 246 (43.6%) reported prior use of antibiotics without a prescription, and 177 (31.4%) reported intent to use antibiotics without a prescription. If feeling sick, respondents endorsed that they would take antibiotics obtained from friends/relatives (22.3% of 564), purchased in the United States without a prescription (19.1%), or purchased abroad without a prescription (17.9%). Younger age, lack of health insurance, and a perceived high cost of doctor visits were predictors of intended use of nonprescription antibiotics from any of the sources. Other predictors of intended use were lack of transportation for medical appointments, language barrier to medical care, Hispanic or Latino ethnicity, and being interviewed in Spanish.

Conclusions

Patients without health insurance who report a financial barrier to care are likely to pursue more dangerous nonprescription antimicrobials. This is a harm of the US fragmented, expensive healthcare system that may drive increasing antimicrobial resistance and patient harm.
Invasive investigation: uptake and transport of l-leucine in the gill epithelium of crustaceans
Authors: Griffin Robert A , Boyd Aaron , Weinrauch Alyssa , Blewett Tamzin A
Published: April 2023

Many aquatic species are well known as extremely successful invaders. The green crab (Carcinus maenas) is an arthropod native to European waters; however, it is now known to be a globally invasive species. Recently, it was discovered that the C. maenas could transport nutrients in the form of amino acids across their gill from the surrounding environment, a feat previously thought to be impossible in arthropods. We compared the ability for branchial amino acid transport of crustacean's native to Canadian Pacific waters to that of the invasive C. maenas, determining if this was a novel pathway in an extremely successful invasive species, or a shared trait among crustaceans. Active transport of l-leucine was exhibited in C. maenas, Metacarcinus gracilis, Metacarcinus magister, and Cancer productus across their gill epithelia. Carcinus maenas exhibited the highest maximum rate of branchial l-leucine transport at 53.7 ± 6.24 nmolg−1 h−1, over twice the rate of two native Canadian crustaceans. We also examined the influence of feeding, gill specificity, and organ accumulation of l-leucine. Feeding events displayed a heavy influence on the branchial transport rate of amino acids, increasing l-leucine transport rates by up to 10-fold in C. maenas. l-leucine displayed a significantly higher accumulation rate in the gills of C. maenas compared to the rest of the body at 4.15 ± 0.78 nmolg−1 h−1, with the stomach, hepatopancreas, eyestalks, muscle tissue, carapace and heart muscle exhibiting accumulation under 0.15 nmolg−1 h−1. For the first time, the novel transport of amino acids in Canadian native arthropods is described, suggesting that branchial amino acid transport is a shared trait among arthropods, contrary to existing literature. Further investigation is required to determine the influence of environmental temperature and salinity on transport in each species to outline any competitive advantages of the invasive C. maenas in a fluctuating estuarine environment.
What if your patient switches from Dr. Google to Dr. ChatGPT? A vignette-based survey of the trustworthiness, value, and danger of ChatGPT-generated responses to health questions
Authors: Van Bulck Liesbet , Moons Philip
Published: April 2023

ChatGPT is a new artificial intelligence system that revolutionizes the way how information can be sought and obtained. In this study, the trustworthiness, value, and danger of ChatGPT-generated responses on four vignettes that represented virtual patient questions were evaluated by 20 experts in the domain of congenital heart disease, atrial fibrillation, heart failure, or cholesterol. Experts generally considered ChatGPT-generated responses trustworthy and valuable, with few considering them dangerous. Forty percent of the experts found ChatGPT responses more valuable than Google. Experts appreciated the sophistication and nuances in the responses but also recognized that responses were often incomplete and sometimes misleading.
Lacustrine speciation associated with chromosomal inversion in a lineage of riverine fishes
Authors: MacGuigan Daniel J , Krabbenhoft Trevor J , Harrington Richard C , Wainwright Dylan K , Backenstose Nathan J C , Near Thomas J
Published: April 2023

Geographic isolation is the primary driver of speciation in many vertebrate lineages. This trend is exemplified by North American darters, a clade of freshwater fishes where nearly all sister species pairs are allopatric and separated by millions of years of divergence. One of the only exceptions is the Lake Waccamaw endemic Etheostoma perlongum and its riverine sister species Etheostoma maculaticeps, which have no physical barriers to gene flow. Here we show that lacustrine speciation of E. perlongum is characterized by morphological and ecological divergence likely facilitated by a large chromosomal inversion. While E. perlongum is phylogenetically nested within the geographically widespread E. maculaticeps, there is a sharp genetic and morphological break coinciding with the lake–river boundary in the Waccamaw River system. Despite recent divergence, an active hybrid zone, and ongoing gene flow, analyses using a de novo reference genome reveal a 9 Mb chromosomal inversion with elevated divergence between E. perlongum and E. maculaticeps. This region exhibits striking synteny with known inversion supergenes in two distantly related fish lineages, suggesting deep evolutionary convergence of genomic architecture. Our results illustrate that rapid, ecological speciation with gene flow is possible even in lineages where geographic isolation is the dominant mechanism of speciation.
Sex-specific selection patterns in a dioecious insect-pollinated plant
Authors: Barbot Estelle , Dufaÿ Mathilde , De Cauwer Isabelle
Published: April 2023

Competition for mate acquisition is the hallmark of any sexual organism. In insect-pollinated plants, competition to attract pollinators is expected to result in pollinator-mediated selection on attractive floral traits. This could overlap with sexual selection if the number of mating partners increases with pollinator attraction, resulting in an improved reproductive success. In this study, we measured a set of floral traits and estimated individual fitness in male and female Silene dioica in an experimental population. Results align with the predictions of Bateman’s principles, in the absence of pollen limitation. In females, natural selection acted on traits that are typically linked with fertility (number of flowers and number of gametes), and selection strength was similar in open- and hand-pollinated females, suggesting a limited role of pollinator-mediated selection. In males, flowering duration and corolla width were positively associated with both reproductive success and number of mates, suggesting that sexual selection has played a role in the evolution of these traits. The use of Bateman’s metrics further confirmed stronger sexual selection in males than in females. Taken together, our results shed light on the occurrence of sex-specific patterns of selection in an insect-pollinated plant population.
Weaker selection on genes with treatment-specific expression consistent with a limit on plasticity evolution in Arabidopsis thaliana
Authors: Roberts Miles , Josephs Emily B
Published: April 2023

Differential gene expression between environments often underlies phenotypic plasticity. However, environment-specific expression patterns are hypothesized to relax selection on genes, and thus limit plasticity evolution. We collated over 27 terabases of RNA-sequencing data on Arabidopsis thaliana from over 300 peer-reviewed studies and 200 treatment conditions to investigate this hypothesis. Consistent with relaxed selection, genes with more treatment-specific expression have higher levels of nucleotide diversity and divergence at nonsynonymous sites but lack stronger signals of positive selection. This result persisted even after controlling for expression level, gene length, GC content, the tissue specificity of expression, and technical variation between studies. Overall, our investigation supports the existence of a hypothesized trade-off between the environment specificity of a gene’s expression and the strength of selection on said gene in A. thaliana. Future studies should leverage multiple genome-scale datasets to tease apart the contributions of many variables in limiting plasticity evolution.
Genome-wide temperature-sensitivity of Polycomb group regulation and reduction thereof in temperate Drosophila melanogaster
Authors: Voigt Susanne , Froschauer Christin
Published: April 2023

Epigenetic regulation varies with the environment. In the fruit fly Drosophila melanogaster, environmental temperature can affect chromatin-based gene regulation. Genes regulated by the Polycomb group can vary in their transcriptional output in response to changes in temperature, which typically increases with decreasing temperature. Here, we studied temperature-sensitive expression of Polycomb group target genes on a genome-wide scale, as well as temperature-sensitive enrichment of two histone modifications associated with the regulation of Polycomb group target genes, H3K27me3 and H3K4me3. We investigated temperature-sensitivity in adult flies, and possible differences thereof between populations adapted to temperate and tropical climates. Compared to genes not targeted by the Polycomb group, an elevated number of target genes showed higher expression at the lower temperature, as it is typically observed for Polycomb group regulation. Many of the Polycomb group target genes also exhibited temperature-sensitive H3K4me3 enrichment in the same direction, and the H3K4me3 temperature response correlated positively with that of expression. A small set of target sites also showed temperature-sensitive enrichment of H3K27me3, again with a higher proportion corresponding to increased transcriptional activation at the lower temperature. Overall, higher transcriptional activity at lower temperature was less pronounced in males compared to females, and in temperate compared to tropical flies. Possible trans- and cis-acting factors responsible for reduced expression plasticity in temperate flies were identified, including factors belonging to the Trithorax group and insulator binding proteins, respectively.
Topological equivalence of linear time-varying control systems
Authors: Li Jing , Zhang Zhixiong
Published: April 2023

In this paper, we mainly studied the topological equivalence of linear time-varying (LTV) control system $\dot{x}\left ( t\right )=A(t)x(t)+B(t)u(t)$ defined on an interval $I \subset \mathbb{R}^{+}$. After giving a new definition of the topological equivalence, we investigated the local equivalence of LTV control systems under two new hypotheses. These hypotheses were made by the local behavior of Krylov indices (which turned out to be controllability indices for the linear time-invariant (LTI) control systems). It was found out that Krylov indices play an important role in the classification problem of LTV control systems. Compared with our former work on the topological equivalence of LTI control systems, new methods and techniques were taken to deal with new difficulties occurred for LTV control systems.
Effects of early intermittent maternal separation on behavior, physiological, and growth performance in piglets
Authors: Cheng Zheng , Zhou Si-Tong , Zhang Xiao-Hong , Fu Qin , Yang Yue , Ji Wen-Bo , Liu Hong-Gui
Published: April 2023

In pig production, the management of piglets by batch lactation due to the increase in litter sizes of sows may result in intermittent early neonatal maternal separation (NMS). We speculated that NMS may affect the piglets cognitive growth performance and health. To determine the extent of the effect, 12 litters of crossbred piglets (Large White × Duroc × Min-pig) were used in this trial. Piglets in the control (Con) group (n = 6) were given a standard feeding method during lactation. Piglets in the experimental group (n = 6) were subjected to the NMS model, in which sows were led out of the enclosure with food every day (8:00–11:00 and 13:00–16:00) starting from postnatal day (PND) 7. During the separation, the piglets were supplemented with milk. All experimental piglets were weaned on PND 35. The piglets were observed for aggression, play, mutual sniffing, and exploratory behavior on PNDs 7, 8, 21, 22, 34, 35, 38, 39, 51, 52, 64, and 65. Physiological indicators, namely serum adrenaline, cortisol, interleukin (IL)-1β, IL-4, IL-6, and tumor necrosis factor (TNF)-α were measured on PNDs 35, 38, and 65, while piglet growth performance was evaluated during suckling and 1 month after weaning. The results showed that aggressive behavior in the MS group was significantly higher than that in the Con group (P < 0.05). Playful and mutual sniffing behaviors in the MS group were significantly lower than those in the Con group except for PNDs 38 and 39 (P < 0.05). Active exploratory behavior in the MS group was significantly higher than that in the Con group on PNDs 7 and 8, and PNDs 21 and 22 (P < 0.05). The frequency of belly-nosing behavior was significantly higher in the MS group than that in the Con group except for PNDs 64 and 65 (P < 0.05). Compared with the Con group, epinephrine, IL-1β, IL-6, and TNF-α concentrations on PNDs 35, 38, and 65 were significantly increased in the MS group (P < 0.01), while IL-4 concentration was significantly decreased (PND 35: P < 0.05; PNDs 38 and 65: P < 0.01). Compared with the Con group, the piglet diarrhea rate in the MS group during suckling was significantly increased (P < 0.01), the weaning weight was significantly decreased (P < 0.05), and it had no significant effect on the body weight at the end of the trial (P > 0.05). In conclusion, the early intermittent NMS created stress and affected the growth performance of piglets during suckling. However, the growth rate was improved by compensatory measures during late weaning.
Structural insights into recognition of SL4, the UUCG stem-loop, of human U1 snRNA by the ubiquitin-like domain, including the C-terminal tail in the SF3A1 subunit of U2 snRNP
Authors: Nameki Nobukazu , Terawaki Shin-ichi , Takizawa Masayuki , Kitamura Madoka , Muto Yutaka , Kuwasako Kanako
Published: April 2023

The pre-spliceosomal complex involves interactions between U1 and U2 snRNPs, where a ubiquitin-like domain (ULD) of SF3A1, a component of U2 snRNP, binds to the stem-loop 4 (SL4; the UUCG tetraloop) of U1 snRNA in U1 snRNP. Here, we reported the 1.80 Å crystal structure of human SF3A1 ULD (ULDSF3A1) complexed with SL4. The structural part of ULDSF3A1 (res. 704–785) adopts a typical β-grasp fold with a topology of β1-β2-α1-310a-β3-β4-310b-β5, closely resembling that of ubiquitin, except for the length and structure of the β1/β2 loop. A patch on the surface formed by three ULDSF3A1-specific residues, Lys756 (β3), Phe763 (β4) and Lys765 (following β4), contacts the canonical UUCG tetraloop structure. In contrast, the directly following C-terminal tail composed of 786KERGGRKK793 was essentially stretched. The main or side chains of all the residues interacted with the major groove of the stem helix; the RGG residues adopted a peculiar conformation for RNA recognition. These findings were confirmed by mutational studies using bio-layer interferometry. Collectively, a unique combination of the β-grasp fold and the C-terminal tail constituting ULDSF3A1 is required for the SL4-specific binding. This interaction mode also suggests that putative post-translational modifications, including ubiquitination in ULDSF3A1, directly inhibit SL4 binding.
Ferroptosis model system by the re-expression of BACH1
Authors: Irikura Riko , Nishizawa Hironari , Nakajima Kazuma , Yamanaka Mie , Chen Guan , Tanaka Kozo , Onodera Masafumi , Matsumoto Mitsuyo , Igarashi Kazuhiko
Published: April 2023

Ferroptosis is a regulated cell death induced by iron-dependent lipid peroxidation. The heme-responsive transcription factor BTB and CNC homology 1 (BACH1) promotes ferroptosis by repressing the transcription of genes involved in glutathione (GSH) synthesis and intracellular labile iron metabolism, which are key regulatory pathways in ferroptosis. We found that BACH1 re-expression in Bach1−/− immortalized mouse embryonic fibroblasts (iMEFs) can induce ferroptosis upon 2-mercaptoethanol removal, without any ferroptosis inducers. In these iMEFs, GSH synthesis was reduced, and intracellular labile iron levels were increased upon BACH1 re-expression. We used this system to investigate whether the major ferroptosis regulators glutathione peroxidase 4 (Gpx4) and apoptosis-inducing factor mitochondria-associated 2 (Aifm2), the gene for ferroptosis suppressor protein 1, are target genes of BACH1. Neither Gpx4 nor Aifm2 was regulated by BACH1 in the iMEFs. However, we found that BACH1 represses AIFM2 transcription in human pancreatic cancer cells. These results suggest that the ferroptosis regulators targeted by BACH1 may vary across different cell types and animal species. Furthermore, we confirmed that the ferroptosis induced by BACH1 re-expression exhibited a propagating effect. BACH1 re-expression represents a new strategy for inducing ferroptosis after GPX4 or system Xc− suppression and is expected to contribute to future ferroptosis research.
Climate change impacts on the potential worldwide distribution of the soybean pest, Piezodorus guildinii (Hemiptera: Pentatomidae)
Authors: Chen Juhong , Jiang Kun , Wang Shujing , Li Yanfei , Zhang Yaoyao , Tang Zechen , Bu Wenjun
Published: April 2023

The redbanded stink bug, Piezodorus guildinii (Westwood, 1837), is a highly destructive soybean pest native to the Neotropical Region. In the past 60 yr, P. guildinii has been observed to expand its distribution in North and South America, causing significant soybean yield losses. In order to predict the future distribution direction of P. guildinii and create an effective pest control strategy, we projected the potential global distribution of P. guildinii using 2 different emission scenarios, Shared Socioeconomic Pathways 126 and 585, and 3 Earth system models, with the maximum entropy niche model (MaxEnt). Then, the predicted distribution areas of P. guildinii were jointly analyzed with the main soybean-producing areas to assess the impact for different soybean region. Our results showed that temperature is the main environmental factor limiting the distribution of P. guildinii. Under present climate conditions, all continents except Antarctica have suitable habitat for P. guildinii. These suitable habitats overlap with approximately 45.11% of the total global cultivated soybean areas. Moreover, P. guildinii was predicted to expand its range in the future, particularly into higher latitudes in the Northern hemisphere. Countries, in particular the United States, where soybean is widely available, would face a management challenge under global warming. In addition, China and India are also high-risk countries that may be invaded and should take strict quarantine measures. The maps of projected distribution produced in this study may prove useful in the future management of P. guildinii and the containment of its disruptive effects.
Clinical characteristics of primary cutaneous and subcutaneous Ewing sarcoma
Authors: Aiba Hisaki , Kojima Yuki , Shimoi Tatsunori , Sudo Kazuki , Yazaki Shu , Imai Toru , Yoshida Akihiko , Iwata Shintaro , Kobayashi Eisuke , Kawai Akira , Arakawa Ayumu , Ogawa Chitose , Kimura Hiroaki , Yonemori Kan
Published: April 2023

Objective

Given the rarity of cutaneous/subcutaneous Ewing sarcoma, their clinical characteristics remain poorly understood. In this study, we aimed to analyse the clinical characteristics of patients with cutaneous/subcutaneous Ewing sarcoma and review the treatment strategy.

Methods

We reviewed the clinical data of 154 patients with Ewing sarcoma who were treated at our hospital between 2005 and 2019. Amongst these patients, 21 patients with cutaneous/subcutaneous Ewing sarcoma were analysed. As a basic strategy, patients with localized disease received intensive chemotherapy (vincristine–doxorubicin–cyclophosphamide/ifosfamide–etoposide), followed by definitive surgery with or without radiotherapy. In total, 15 patients underwent pre-diagnostic resection with macroscopic residue (seven patients) or non-macroscopic residue (eight patients) before intensive chemotherapy.

Results

The median tumour length of the measurable lesions was 3.2 cm, and the ratio of metastasis was significantly lower than the Ewing sarcoma of other anatomical sites (10% vs. 37%, P = 0.013). Despite the pre-diagnostic resection, local recurrence after additional resection and/or adjuvant radiotherapy did not occur in any of the patients with localized disease. Overall survival was significantly higher in patients with cutaneous/subcutaneous Ewing sarcoma than in patients with Ewing sarcoma of other anatomical sites (hazard ratio = 0.33, P = 0.013). The event-free survival rate of cutaneous/subcutaneous Ewing sarcoma was also superior to that of Ewing sarcoma of other anatomical sites (hazard ratio = 0.35, P = 0.01).

Conclusions

Patients with cutaneous/subcutaneous Ewing sarcoma may have better prognosis than those with Ewing sarcoma at other anatomical sites. Although pre-diagnostic resection without appropriate investigations is not recommended, local control may be recovered by using a combination of additional resection, chemotherapy and radiotherapy.
Wind-assisted high-altitude dispersal of mosquitoes and other insects in East Africa
Authors: Atieli Harrysone E , Zhou Guofa , Zhong Daibin , Wang Xiaoming , Lee Ming-chieh , Yaro Alpha S , Diallo Moussa , Githure John , Kazura James , Lehmann Tovi , Yan Guiyun
Published: April 2023

Knowledge of insect dispersal is relevant to the control of agricultural pests, vector-borne transmission of human and veterinary pathogens, and insect biodiversity. Previous studies in a malaria endemic area of the Sahel region in West Africa revealed high-altitude, long-distance migration of insects and various mosquito species. The objective of the current study was to assess whether similar behavior is exhibited by mosquitoes and other insects around the Lake Victoria basin region of Kenya in East Africa. Insects were sampled monthly from dusk to dawn over 1 year using sticky nets suspended on a tethered helium-filled balloon. A total of 17,883 insects were caught on nets tethered at 90, 120, and 160 m above ground level; 818 insects were caught in control nets. Small insects (<0.5 cm, n = 15,250) were predominant regardless of height compared with large insects (>0.5 cm, n = 2,334) and mosquitoes (n = 299). Seven orders were identified; dipteran was the most common. Barcoding molecular assays of 184 mosquitoes identified 7 genera, with Culex being the most common (65.8%) and Anopheles being the least common (5.4%). The survival rate of mosquitoes, experimentally exposed to high-altitude overnight, was significantly lower than controls maintained in the laboratory (19% vs. 85%). There were no significant differences in mosquito survival and oviposition rate according to capture height. These data suggest that windborne dispersal activity of mosquito vectors of malaria and other diseases occurs on a broad scale in sub-Saharan Africa.
A multivariate pseudo-likelihood approach to estimating directional ocean wave models
Authors: Grainger Jake P , Sykulski Adam M , Ewans Kevin , Hansen Hans F , Jonathan Philip
Published: April 2023

Buoy data in the form of multivariate time series are routinely recorded at many locations in the world’s oceans. Such data can help characterise the ocean wavefield by modelling the frequency-direction spectrum. State-of-the-art methods for estimating the parameters of such models do not make use of the full spatiotemporal content of the buoy observations due to unnecessary assumptions and smoothing. We explain how the multivariate debiased Whittle likelihood can be used to jointly estimate all parameters of such frequency-direction spectra directly from recorded time series. We apply the method to North Sea buoy data and discuss challenging practical issues.
Estimating subject-specific hazard functions
Authors: Chatterjee Moumita , Ganguli Bhaswati , Sen Roy Sugata
Published: April 2023

The central idea of this paper is to compare mean responses of several subjects in the presence of censoring and subject-specific variation. We develop a semiparametric mixed model for fitting subject-specific hazard curves to a set of censored failure times. A spline-based model and a mixed effects framework for smoothing are used. Efficient estimators of fixed parameters and predictors of the random components are derived and their asymptotic properties studied. This is a generalization of the method proposed by [Cai, T., Hyndman, R. J., & Wand, M. P. (2002). Mixed model-based hazard estimation. Journal of Computational and Graphical Statistics, 11(4), 784–798. https://doi.org/10.1198/106186002862] to incorporate additional subject-specific variation of the hazard function. The results are illustrated using two motivating examples.
Interleukin 10, but not tumor necrosis factor-alpha, gene variations are associated with factor VII inhibitor development
Authors: Ramezanpour Nahid , Khanaki Korosh , Dorgalaleh Akbar , Shams Mahmood , Elmi Ali , Zaker Farhad
Published: April 2023

Objective

Development of alloantibodies against coagulation factor VII (FVII) is the main therapeutic challenge in severe congenital FVII deficiency. About 7% of patients with severe congenital FVII deficiency develop an inhibitor against FVII. In this research, the relationship between interleukin (IL)-10 and tumor necrosis factor-alpha (TNF)-α gene variants and inhibitor development was evaluated for a group of Iranian patients with severe congenital factor VII deficiency.

Methods

Patients with FVII deficiency were divided into 2 groups: 6 cases and 15 controls. Genotyping was performed using the amplification-refractory mutation system polymerase chain reaction.

Results

We found that IL-10 rs1800896 A>G gene variant is associated with the risk of FVII inhibitor development (OR = 0.077, 95% CI = 0.016–0.380, P = .001), whereas the TNFα-rs1800629G>A variant has no relation with inhibitor development in severe FVII deficiency.

Conclusion

The results show that the IL-10 rs1800896 A>G variant increases the risk of developing an inhibitor in patients with severe congenital FVII deficiency.
Optimization of laboratory diagnosis of heparin-induced thrombocytopenia using HemosIL-AcuStar-HIT-IgG assay
Authors: Tucker Catherine M , Rhoades Ruben , Sharma Ruchika , Gong Jerald Z
Published: April 2023

Objective

The aim of this study was to determine an optimal cutoff value for the newly available HemosIL-AcuStar-HIT-IgG assay (AcuStar) for the diagnosis of heparin-induced thrombocytopenia (HIT).

Method

We evaluated the performance of AcuStar using serotonin release assay (SRA) as the gold standard and incorporated 4T score calculation in a cohort of suspected HIT cases. Statistical analysis was performed to determine optimal cutoff value for the diagnosis of HIT.

Result

A diagnosis of HIT can be excluded with a platelet factor 4 (PF4) value of <0.4 U/mL by AcuStar and 4T score in the low-risk category (≤3). All other cases will require confirmation with a functional test.

Conclusion

Our study resulted in the implementation of a diagnostic algorithm for laboratory diagnosis of HIT, which incorporates pretest calculation of 4T score and AcuStar as a screening test, with reflex confirmation by SRA. This new algorithm resulted in extended hours of test availability and a more rapid turnaround time in reporting PF4 results.
Slowly drifting radio fibres
Authors: Chernov G P , Fomichev V V
Published: April 2023

The fine structure in the continuum radiation of type IV solar radio bursts is very rich in various structures (zebra structure, fibres, pulsations, spikes, etc.). So far, however, no attention has been paid to the isolated fibres that occasionally appear in the metre and decimetre ranges. Here we give and discuss examples of the dynamic spectra of such bursts obtained many years ago (in the metre waveband from 1969) as well in recent years (in the decimetre and microwave wavebands from 2003–2013). Isolated fibres are observed mostly in the decimetre range (although there are examples in both the metre and microwave ranges), and they reveal a number of features of classical fibre bursts. As a generation mechanism for such fibres, the process of interaction of whistlers with Langmuir plasmons was suggested. An analysis of conditions for the realization of this process in solar magnetic arch structures and its efficiency was carried out. Estimates of the intensity of low-frequency turbulence (whistlers) and magnetic field strength in the solar corona were obtained using the data of radio fibres.
Looking time studies and eye tracking in infancy
Authors: Althaus Nadja
Published: April 2023

Using infants’ gaze to track their overt attention has been one of the most successful methods to obtain insight into cognitive development, including some fundamental paradigms in infancy research such as preferential looking and habituation/familiarization. The availability of automatic remote eye tracking has not just made looking time studies widely accessible, but also offers new approaches such as tracking gaze directed at small areas-of-interest, pupillometry, and gaze-contingent eye tracking. This chapter first covers eye movements as a behavioral metric in infant studies, then reviews classic looking time methods and their application in cognitive development, and finally turns to novel approaches to studying infant eye gaze that have been made possible by automatic eye tracking.
Women, Hospitality and The Intimate Politics of International Socialism, 1955–1965
Authors: Lewis Su Lin
Published: April 2023

In the 1950s, a commitment to democratic socialism connected networks of intellectuals, activists and political operators in both Europe and Asia. Many of these were women, who built informal and intimate networks of solidarity that underpinned the movement. The rich set of correspondence between European and Asian socialist women speaks to their role as connectors of global and local civil society within international socialist circuits. It also indicates the importance of friendship, mobility and hospitality as a crucial factor in sustaining such networks, as well as building the trust that facilitated the exchange of subversive information. While Asia was seen as the great hope of international socialism in the 1950s, by the middle of the 1960s, many of its socialist parties had imploded, pointing to the limits of international socialism for Asian women amidst global anti-communism and the rise of authoritarian states. Transnational socialist networks nonetheless helped further both European and Asian women’s campaigns for gender equality, development and democratic socialism in decolonizing Asia, adding vital new dimensions to the history of internationalism.
The Fundamental Role of H2O in the Generation of Coeval Sodic and Potassic Granitoids at Continental Arcs: An Example from the Yangtze Block, South China
Authors: Qi Han , Zhao Jun-Hong , Johnson Tim E
Published: April 2023

The bulk rock composition of granitoids reflects the composition of their source and the conditions of partial melting, which are functions of the geodynamic setting in which they formed. Granitoids in active continental margins (continental arcs) are dominated by calc-alkaline rocks with subordinate alkaline compositions, although how these different magma compositions formed is not well understood. Neoproterozoic magmatic rocks are widely distributed along the western margin of the Yangtze Block in South China to form the >1000-km long Panxi continental arc system, which is dominated by granitoids with minor mafic–ultramafic and intermediate plutons. The granitoids are subdivided into sodic and potassic variants that occur as belts along the western and eastern sides of the continental arc, respectively. Sodic granitoids from the western part consist of tonalite, granodiorite, and monzogranite with crystallisation ages ranging from 870 Ma to 740 Ma. They have low K2O/Na2O ratios (0.1–1.0) and high Na2O contents (3.5–6.7 wt%), high but variable SiO2 (61–75 wt%) concentrations, and negative to positive whole-rock εNd(t) values (−1.7 to +2.9). Zircon grains from the sodic granitoids have εHf(t) values ranging from +0.3 to +9.6 and δ18O from 3.90‰ to 7.71‰. The potassic granitoids from the eastern side consist of monzogranite and syenogranite with crystallisation ages from 820 Ma to 790 Ma. They have high K2O/Na2O ratios (0.6–2.2), K2O (2.6–5.9 wt%) and SiO2 contents (69–78 wt%), but whole-rock εNd(t) (−0.9 to +2.9) and zircon εHf(t) (+1.8 to +12.9), and δ18O values (2.98‰ to 6.41‰) similar to those of the sodic granitoids. The isotopic compositions of both the sodic and potassic granitoids are similar to those of spatially- and temporally-related mantle-derived (mafic to ultramafic) rocks, and are considered to have been derived from juvenile mafic continental crust. Phase equilibrium modelling shows that the H2O content of the granitoid source rocks played a key role in their petrogenesis, both in lowering solidus temperatures and in controlling the compositions of the derived partial melts. Our results indicate that calc-alkaline sodic granitoids can be formed by water-fluxed melting of juvenile mafic crust at 750–900°C and 9–12 kbar in which the required H2O was derived from the dewatering of underplating mafic arc magmas. By contrast, the potassic granitoids were generated by fluid-absent (H2O-undersaturated) partial melting of a similar juvenile mafic source at 725–900°C and 6–9 kbar. We conclude that the sodic granitoids were derived from partial melting of the newly-formed mafic lower crust in the continental arc, whereas the potassic granitoids were likely generated in the back-arc setting induced by upwelling of asthenospheric mantle.