bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidation Driven Reversal of PIP2-dependent Gating in GIRK2 Channels
Authors: Lee Sun-Joo , Maeda Shoji , Gao Jian , Nichols Colin G 
Published: April 2023

Abstract
Physiological activity of G protein gated inward rectifier K+ (GIRK, Kir3) channel, dynamically regulated by three key ligands, phosphoinositol-4,5-bisphosphate (PIP2), Gβγ, and Na+, underlies cellular electrical response to multiple hormones and neurotransmitters in myocytes and neurons. In a reducing environment, matching that inside cells, purified GIRK2 (Kir3.2) channels demonstrate low basal activity, and expected sensitivity to the above ligands. However, under oxidizing conditions, anomalous behavior emerges, including rapid loss of PIP2 and Na+-dependent activation and a high basal activity in the absence of any agonists, that is now paradoxically inhibited by PIP2. Mutagenesis identifies two cysteine residues (C65 and C190) as being responsible for the loss of PIP2 and Na+-dependent activity and the elevated basal activity, respectively. The results explain anomalous findings from earlier studies and illustrate the potential pathophysiologic consequences of oxidation on GIRK channel function, as well as providing insight to reversed ligand-dependence of Kir and KirBac channels.
Single-Cell RNA Sequencing Reveals Microevolution of the Stickleback Immune System
Authors: Fuess Lauren E , Bolnick Daniel I 
Published: April 2023

AbstractThe risk and severity of pathogen infections in humans, livestock, or wild organisms depend on host immune function, which can vary between closely related host populations or even among individuals. This immune variation can entail between-population differences in immune gene coding sequences, copy number, or expression. In recent years, many studies have focused on population divergence in immunity using whole-tissue transcriptomics. But, whole-tissue transcriptomics cannot distinguish between evolved differences in gene regulation within cells, versus changes in cell composition within the focal tissue. Here, we leverage single-cell transcriptomic approaches to document signatures of microevolution of immune system structure in a natural system, the three-spined stickleback (Gasterosteus aculeatus). We sampled nine adult fish from three populations with variability in resistance to a cestode parasite, Schistocephalus solidus, to create the first comprehensive immune cell atlas for G. aculeatus. Eight broad immune cell types, corresponding to major vertebrate immune cells, were identified. We were also able to document significant variation in both abundance and expression profiles of the individual immune cell types among the three populations of fish. Furthermore, we demonstrate that identified cell type markers can be used to reinterpret traditional transcriptomic data: we reevaluate previously published whole-tissue transcriptome data from a quantitative genetic experimental infection study to gain better resolution relating infection outcomes to inferred cell type variation. Our combined study demonstrates the power of single-cell sequencing to not only document evolutionary phenomena (i.e., microevolution of immune cells) but also increase the power of traditional transcriptomic data sets.
Molecular mechanisms underlying hematophagia revealed by comparative analyses of leech genomes
Authors: Zheng Jinghui , Wang Xiaobo , Feng Tong , Rehman Saif ur , Yan Xiuying , Shan Huiquan , Ma Xiaocong , Zhou Weiguan , Xu Wenhua , Lu Liying , Liu Jiasheng , Luo Xier , Cui Kuiqing , Qin Chaobin , Chen Weihua , Yu Jun , Li Zhipeng , Ruan Jue , Liu Qingyou 
Published: April 2023

Abstract

Background
Leeches have been used in traditional Chinese medicine since prehistoric times to treat a spectrum of ailments, but very little is known about their physiological, genetic, and evolutionary characteristics.

Findings
We sequenced and assembled chromosome-level genomes of 3 leech species (bloodsucking Hirudo nipponia and Hirudinaria manillensis and nonbloodsucking Whitmania pigra). The dynamic population histories and genome-wide expression patterns of the 2 bloodsucking leech species were found to be similar. A combined analysis of the genomic and transcriptional data revealed that the bloodsucking leeches have a presumably enhanced auditory sense for prey location in relatively deep fresh water. The copy number of genes related to anticoagulation, analgesia, and anti-inflammation increased in the bloodsucking leeches, and their gene expressions responded dynamically to the bloodsucking process. Furthermore, the expanded FBN1 gene family may help in rapid body swelling of leeches after bloodsucking, and the expanded GLB3 gene family may be associated with long-term storage of prey blood in a leech's body.

Conclusions
The high-quality reference genomes and comprehensive datasets obtained in this study may facilitate innovations in the artificial culture and strain optimization of leeches.
An Enhanced Euler Characteristic of Sutured Instanton Homology
Authors: Li Zhenkun , Ye Fan 
Published: April 2023

Abstract
For a balanced sutured manifold $(M,\gamma )$, we construct a decomposition of $SHI(M,\gamma )$ with respect to torsions in $H=H_{1}(M;\mathbb {Z})$, which generalizes the decomposition of $I^{\sharp }(Y)$ in a previous work of the authors. This decomposition can be regarded as a candidate for the counterpart of the torsion spin$^{c}$ decompositions in $SFH(M,\gamma )$. Based on this decomposition, we define an enhanced Euler characteristic $\chi _{\textrm {en}}(SHI(M,\gamma ))\in \mathbb {Z}[H]/\pm H$ and prove that $\chi _{\textrm {en}}(SHI(M,\gamma ))=\chi (SFH(M,\gamma ))$. This provides a better lower bound on $\dim _{\mathbb {C}}SHI(M,\gamma )$ than the graded Euler characteristic $\chi _{\textrm {gr}}(SHI(M,\gamma ))$. As applications, we prove instanton knot homology detects the unknot in any instanton L-space and show that the conjecture $KHI(Y,K)\cong \widehat {HFK}(Y,K)$ holds for all $(1,1)$-L-space knots and constrained knots in lens spaces, which include all torus knots and many hyperbolic knots in lens spaces.
Structured Immune Workup in Healthy Children With a First Episode of Severe Bacterial Infection: A 7-year Single-Center Study
Authors: Strasser Sophie , Relly Christa , Berger Christoph , Trück Johannes 
Published: April 2023

Abstract

Background
Severe bacterial infections (SBIs) in otherwise healthy children are rare and may represent an underlying impairment of the immune system, including primary immunodeficiency. However, it is unclear whether and how children should be assessed.

Methods
We retrospectively analyzed data from hospital records of previously healthy children aged 3 days to 18 years with SBI, including pleuropneumonia, meningitis, and/or sepsis. Patients were diagnosed or immunologically followed up between 1 January 2013 and 31 March 2020.

Results
Among 432 children with SBI, findings could be analyzed in 360. Follow-up data were available for 265 children (74%), of whom 244 (92%) underwent immunological testing. Laboratory abnormalities were found in 51 of 244 patients (21%), with 3 deaths (1%). Fourteen children (6%) had immunodeficiency considered clinically relevant (3 complement deficiencies, 1 autoimmune neutropenia, 10 humoral immunodeficiencies), and 27 (11%) had milder humoral abnormalities or findings suggestive of delayed adaptive immune maturation.

Conclusions
A substantial proportion of children with SBI may benefit from routine immunological testing, revealing (potentially) clinically relevant impaired immune function in 6%–17% of children. The identification of immune abnormalities allows for specific counseling of families and optimization of preventive measures, such as booster vaccinations, to avoid future SBI episodes.
Effect analysis of multi-department cooperation in improving etiological submission rates before antibiotic treatment
Authors: Lao YiQun , Tang QiJiang , Zeng Juan , Gong WeiWei , Shen YuYing 
Published: April 2023

Abstract
Increased bacterial drug resistance has become a serious global public health problem. The application of antibiotics involves various clinical departments, and the rational application of antibiotics is the key to improving their efficacy. To provide a basis for further improving the etiological submission rate and standardizing the rational use of antibiotics, this article discusses the intervention effect of multi-department cooperation in improving the etiological submission rate before antibiotic treatment. A total of 87 607 patients were divided into a control group (n = 45 890) and an intervention group (n = 41 717) according to whether multi-department cooperation management was implemented. The intervention group involved the patients hospitalized from August to December 2021, while the control group involved the patients hospitalized from August to December 2020. The submission rates of the two groups; the rates before antibiotic treatment at the unrestricted use level, the restricted use level, and the special use level in departments; and the timing of submission were compared and analysed. The overall differences in the etiological submission rates before antibiotic treatment at the unrestricted use level (20.70% vs 55.98%), the restricted use level (38.23% vs 66.58%), and the special use level (84.92% vs 93.14%) were statistically significant before and after intervention (P &lt; .05). At a more specific level, the etiological submission rates of different departments before antibiotic treatment at the unrestricted use level, the restricted use level, and the special use level were improved, but the special activities of multi-department cooperation management did not improve the submission timing significantly. Multi-department cooperation can effectively improve the etiological submission rates before antimicrobial treatment, but it is necessary to improve measures for specific departments to improve long-term management and incentive and restraint mechanisms.
The anti-inflammatory and anti-oxidative effect of a classical hypnotic bromovalerylurea mediated by the activation of NRF2
Authors: Takeda Haruna , Nakajima Yoshihiro , Yamaguchi Teruaki , Watanabe Itaru , Miyoshi Shoko , Nagashio Kodai , Sekine Hiroki , Motohashi Hozumi , Yano Hajime , Tanaka Junya 
Published: April 2023

Abstract
The Kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2 (KEAP1–NRF2) system plays a central role in redox homeostasis and inflammation control. Oxidative stress or electrophilic compounds promote NRF2 stabilization and transcriptional activity by negatively regulating its inhibitor, KEAP1. We have previously reported that bromovalerylurea (BU), originally developed as a hypnotic, exerts anti-inflammatory effects in various inflammatory disease models. However, the molecular mechanism underlying its effect remains uncertain. Herein, we found that by real-time multicolor luciferase assay using stable luciferase red3 (SLR3) and green-emitting emerald luciferase (ELuc), BU potentiates NRF2-dependent transcription in the human hepatoblastoma cell line HepG2 cells, which lasted for more than 60 h. Further analysis revealed that BU promotes NRF2 accumulation and the transcription of its downstream cytoprotective genes in the HepG2 and the murine microglial cell line BV2. Keap1 knockdown did not further enhance NRF2 activity, suggesting that BU upregulates NRF2 by targeting KEAP1. Knockdown of Nfe2l2 in BV2 cells diminished the suppressive effects of BU on the production of pro-inflammatory mediators, like nitric oxide (NO) and its synthase NOS2, indicating the involvement of NRF2 in the anti-inflammatory effects of BU. These data collectively suggest that BU could be repurposed as a novel NRF2 activator to control inflammation and oxidative stress.
MPARN: multi-scale path attention residual network for fault diagnosis of rotating machines
Authors: Kim Hyeongmin , Park Chan Hee , Suh Chaehyun , Chae Minseok , Yoon Heonjun , Youn Byeng D 
Published: April 2023

Abstract
Multi-scale convolutional neural network structures consisting of parallel convolution paths with different kernel sizes have been developed to extract features from multiple temporal scales and applied for fault diagnosis of rotating machines. However, when the extracted features are used to the same extent regardless of the temporal scale inside the network, good diagnostic performance may not be guaranteed due to the influence of the features of certain temporal scale less related to faults. Considering this issue, this paper presents a novel architecture called a multi-scale path attention residual network to further enhance the feature representational ability of a multi-scale structure. Multi-scale path attention residual network adopts a path attention module after a multi-scale dilated convolution layer, assigning different weights to features from different convolution paths. In addition, the network is composed of a stacked multi-scale attention residual block structure to continuously extract meaningful multi-scale characteristics and relationships between scales. The effectiveness of the proposed method is verified by examining its application to a helical gearbox vibration dataset and a permanent magnet synchronous motor current dataset. The results show that the proposed multi-scale path attention residual network can improve the feature learning ability of the multi-scale structure and achieve better fault diagnosis performance.
Circulating IgG antibodies to periodontal bacteria and lung cancer risk in the CLUE cohorts
Authors: Ampomah Nana K , Teles Flavia , Martin Lynn M , Lu Jiayun , Koestler Devin C , Kelsey Karl T , Beck James D , Platz Elizabeth A , Michaud Dominique S 
Published: April 2023

Abstract

Background
Oral health is a key indicator of overall health, well-being, and quality of life. Several studies have provided new evidence about the role of oral diseases, specifically periodontitis, in generating risk for various forms of cancers, including lung, colorectal, and pancreatic cancers.

Methods
Incident lung cancer cases (n = 192) and matched controls (n = 192) were selected from participants of the CLUE I and CLUE II cohorts. Archived serum samples collected from participants in 1974 (in CLUE I) were analyzed using immunoblotting for immunoglobulin G (IgG) antibody levels to 13 bacteria of the periodontium. Associations between antibody levels and lung cancer were estimated using conditional logistic regression.

Results
Most of the periodontal bacterial antibodies measured were inversely associated with lung cancer risk; of these, 3 were statistically significant (Prevotellaintermedia, Actinomyces naeslundii, and Veillonella parvula). A statistically significant positive association was observed for one of the Porphyromonas gingivalis strains after adjusting for P. intermedia. The sum of the logarithm of antibodies against the 13 measured bacteria was inversely associated with risk of lung cancer when the analysis was restricted to a longer follow-up (31-44 years after blood collection, highest vs lowest quartile: odds ratio = 0.26, 95% confidence interval = 0.08 to 0.84).

Conclusions
Findings from this study highlight the complexity of using serum IgG antibodies to periodontal bacteria to identify associations between oral pathogens and risk of lung cancer. The inverse associations observed for antibodies to periodontal bacteria suggest that these may represent markers of immunity that provide some advantage in reducing the development of lung cancer.
The Role of Incremental and Superficial Processing in the Depth Charge Illusion: Experimental and Modeling Evidence
Authors: Paape Dario 
Published: April 2023

Abstract
The depth charge illusion occurs when compositionally incongruous sentences such as No detail is too unimportant to be left out are assigned plausible non-compositional meanings (Don’t leave out details). Results of two online reading and judgment experiments show that moving the incongruous degree phrase to the beginning of the sentence in German (lit. “Too unimportant to be left out is surely no detail”) results in an attenuation of this semantic illusion, implying a role for incremental processing. Two further experiments show that readers cannot consistently turn the communicated meaning of depth charge sentences into its opposite, and that acceptability varies greatly between sentences and subjects, which is consistent with superficial interpretation. A meta-analytic fit of the Wiener diffusion model to data from six experiments shows that world knowledge is a systematic driver of the illusion, leading to stable acceptability judgments. Other variables, such as sentiment polarity, influence subjects’ depth of processing. Overall, the results shed new light on the role of superficial processing on the one hand and of communicative competence on the other hand in creating the depth charge illusion. I conclude that the depth charge illusion combines aspects of being a persistent processing “bug” with aspects of being a beneficial communicative “feature”, making it a fascinating object of study.
A giant metanephric adenoma in a young male
Authors: Mremi Alex , Bodganowics Jack , Sadiq Adnan , Tadayo Joshua , Lodhia Jay 
Published: April 2023

AbstractMetanephric adenoma is an uncommon renal tumor with almost exclusively benign behavior, which can clinically and radiologically imitate malignancy. The histological examination is therefore crucial in diagnosis. Herein, we report a case of an 18-year-old male with a huge left renal mass. Histopathology and immunohistochemistry of nephrectomy resection specimen confirmed it to be metanephric adenoma. We present our experience with this rare tumor entity and literature review with focusing on differential diagnosis.
Menstrual cycle–driven vs noncyclical daily changes in sexual desire
Authors: Kiesner Jeff , Bittoni Celeste , Eisenlohr-Moul Tory , Komisaruk Barry , Pastore Massimiliano 
Published: April 2023

Abstract

Background
Past research on the association between sexual desire and the menstrual cycle has provided inconclusive results and has not considered the potential influence of psychological and physical changes that are frequently associated with the menstrual cycle.

Aim
To test the strength of association between the menstrual cycle (and associated symptoms) and changes in sexual desire.

Methods
Prospective daily reports across 2 full menstrual cycles (2 months) from a sample of female university students (n = 213), were analysed. Analyses tested for average effects of the menstrual cycle on sexual desire, individual differences in these effects, and cyclical and noncyclical associations between sexual desire and the 9 menstrual cycle–related changes. Note that data presented in the current article come from a larger study from which other reports have been published.

Outcomes
Target variables were (1) daily change in sexual desire and (2) daily reports of 5 psychological changes and 4 physical changes that are commonly associated with the menstrual cycle.

Results
Results showed that when considering average effects across participants, the menstrual cycle was associated with a small midcycle increase in sexual desire. However, multilevel analyses showed large individual differences in how the menstrual cycle influences sexual desire. Specifically, some participants showed a midcycle increase, others a perimenstrual increase, and others no change across the menstrual cycle. Moreover, results demonstrated that psychological changes were more important for predicting sexual desire as compared with physical changes.

Clinical Implications
These results suggest that daily measurement of sexual desire across multiple menstrual cycles may be an important tool in the assessment of sexual desire among some females.

Strengths and Limitations
Strengths of this study are the daily assessment of sexual desire and all symptoms for 2 menstrual cycles and multilevel analyses that allow the study of individual differences. Limitations include limited measurement of sexual desire based on only 2 questions and the lack of measures of relationship status and sexual orientation.

Conclusion
Emphasis is placed on the need to apply more rigorous research methods and to abandon simplistic average-effects models that are based on outdated theories and stereotypes.
Genetic susceptibility to cognitive decline following craniospinal irradiation for pediatric central nervous system tumors
Authors: Brown Austin L , Sok Pagna , Raghubar Kimberly P , Lupo Philip J , Richard Melissa A , Morrison Alanna C , Yang Jun J , Stewart Clinton F , Okcu Mehmet Fatih , Chintagumpala Murali M , Gajjar Amar , Kahalley Lisa S , Conklin Heather , Scheurer Michael E 
Published: April 2023

Abstract

Background
Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI.

Methods
Intelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency &gt; 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P &lt; 5 × 10−5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P &lt; .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P &lt; 5 × 10−8) in a meta-analysis across ancestry groups.

Results
Participants were mostly males (65%) diagnosed with embryonal tumors (98%) at a median age of 8.3 years. Overall, 1150 neurocognitive evaluations were obtained (median = 5, range: 2–10 per participant). One of the five loci previously associated with cognitive outcomes in pediatric CNS tumors survivors demonstrated significant time-dependent IQ declines (PPARA rs6008197, P = .004). Two variants associated with IQ in the general population were associated with declines in IQ after Bonferroni correction (rs9348721, P = 1.7 × 10−5; rs31771, P = 7.8 × 10−4). In genome-wide analyses, we identified novel loci associated with accelerated declines in IQ (rs116595313, meta-P = 9.4 × 10−9), WM (rs17774009, meta-P = 4.2 × 10−9), and PS (rs77467524, meta-P = 1.5 × 10−8; rs17630683, meta-P = 2.0 × 10−8; rs73249323, meta-P = 3.1 × 10−8).

Conclusions
Inherited genetic variants involved in baseline cognitive functioning and novel susceptibility loci jointly influence the degree of treatment-associated cognitive decline in pediatric CNS tumor survivors.