bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECTIVENESS OF SPIRITUAL SUPPORT FOR CANCER PATIENTS TO IMPROVE THE QUALITY OF LIFE: A LITERATURE REVIEW
Authors: Rupang Ernita Rante , Rumambo Pandin Moses Glorino , Yunitasari Esti
Published: November 2023

Background

The efficacy of spiritual support for cancer patients is crucial in the course of treatment. As a result, it is crucial to consider the mentoring techniques employed. The purpose of this review of the literature is to methodically look at worldwide research from the previous ten years that has been published in English-language journals from different nations that relates to the usefulness of spiritual support for cancer patients to improve quality of life

Method

The method used in this literature review is by database search strategy: data search using a systematic and comprehensive electronic database from several indexing and hand searching. The following indexes were searched for research data: Scopus, CINAHL, PubMed, and Proquest. By utilizing the search terms “OR” spirituality accompanying “AND” quality of life, spirituality support. The eligibility requirements established by the PICO model (Population, Intervention, Comparison/controls, Outcome) were taken into consideration when conducting the article search. Population: cancer patients, Intervention: Spiritual support, Comparison: Intervention provided, Outcome: Improved quality of life.

The process of selecting and extracting data involves stating the problem to be studied, pertinent groups, intervention to be provided, and results to be measured. The author then goes on to clarify the selection and analysis process by outlining the specific inclusion and exclusion criteria as follows:The inclusion criteriafor the articles reviewed were: the article had to be a full paper, the research subjects were cancer patients, the intervention carried out was spiritual assistance with a comparison of cancer patients without usual care spiritual assistance. An improvement in cancer patients’ quality of life is the search’s result.The exclusion criteriafor articles reviewed are: articles other than English, research articles before 2017 and articles that are not free access

Result

11 articles were examined. Focuses on providing spiritual support to cancer sufferers, including how to do it and the results. Spiritual support provided through a variety of techniques, including mindfulness, meditation, music therapy, and telephone counseling, encourages patients to be more passionate about their treatments and enhances their quality of life. The patient is religious preferences should be taken into consideration when providing care.

Conclusion

Spiritual support has a positive impact on a cancer patient is quality of life by giving them a sense of calm and desire to keep going through the treatment and their daily lives. Through improving coping mechanisms, bringing patients closer to something transcendent (God), and providing a sense of comfort for cancer patients going through chemotherapy, spiritual assistance techniques like mindfulness, listening to music, and counseling can help patients improve their quality of life.
Assessing Occupational Hazards and Factors Contributing to the Health Effects Faced By Female Market Traders in Nakasero Market, Central Kampala Uganda
Authors: Ronald Waneloba
Published: November 2023

Background

In Uganda, the informal sector, particularly public markets, presents a concerning array of unregulated workplace hazards, predominantly affecting female traders. These hazards pose significant threats to the health of female market traders, who make up the majority of the workforce. However, there has been limited attention given to identifying and addressing the occupational risks faced by these women. This study aimed to assess the occupational hazards and the contributing factors to health effects among female market traders in Nakasero market, central Kampala.

Methods

A descriptive cross-sectional study was conducted among female market traders in Nakasero market, central Kampala. The study employed a mixed-methods approach, utilizing both quantitative and qualitative methods. Data collection involved face-to-face, interviewer-administered, semi-structured questionnaires and key informant interviews. Quantitative data were analyzed using EPIDATA 3.02, STATA 14, and Microsoft Excel, while qualitative data were subjected to deductive thematic analysis.

Results

The hazards encompassed biological risks, where a significant proportion reported suffering from mosquito bites within the market (87.36%), and urinary tract infections (UTIs) attributed to microorganisms stemming from unclean toilet facilities (80.46%). Furthermore, the investigation revealed the presence of physical, ergonomic, and psychological hazards, all of which posed a threat to the health of female market traders.

Various factors contributed to the health effects experienced by these traders. Notably, many of them endured prolonged working hours without adequate rest or sleep, with 47% of female market traders spending over 12 hours in the market. The study also found that a majority of respondents failed to use personal protective equipment (PPE), totaling 70.49%. Additionally, a substantial portion (42%) admitted to not practicing proper hand hygiene while in the market. Issues related to sanitary facilities were prevalent, including a shortage of toilet stalls, unclean conditions, and occasional water shortages. Poor market infrastructure, inadequate working space, and overcrowding further compounded the challenges faced by female market traders.

The health effects and problems reported by these traders encompassed a spectrum of issues, including musculoskeletal pain, malaria, UTIs, respiratory problems, COVID-19, skin conditions, headaches, and obesity.

Conclusion

This study underscores the ongoing occupational hazards and health effects faced by female market traders in public markets throughout Uganda, arising from a combination of various contributing factors. Addressing these issues is crucial to safeguard the well-being of these women and improve their working conditions.
Hypoxia inducible factors inhibit respiratory syncytial virus infection by modulation of nucleolin expression
Authors: Zhuang Xiaodong , Gallo Giulia , Sharma Parul , Ha Jiyeon , Magri Andrea , Borrmann Helene , Harris James M , Tsukuda Senko , Bentley Eleanor , Kirby Adam , Neck Simon de , Yang Hongbing , Balfe Peter , Wing Peter AC , Matthews David , Harris Adrian L , Kipar Anja , Stewart James P , Bailey Dalan , McKeating Jane A
Published: November 2023

Respiratory syncytial virus (RSV) is a global healthcare problem, causing respiratory illness in young children and elderly individuals. However, our knowledge of the host pathways that define susceptibility to RSV infection and disease severity is limited. Hypoxia inducible factors (HIFs) define cellular metabolic processes in response to low oxygen and are recognised to play a key role in regulating inflammatory responses in the lower respiratory tract. We demonstrate a role for hypoxia inducible factors (HIFs) to suppress RSV entry and RNA replication. We show that hypoxia and HIF prolyl-hydroxylase inhibitors significantly reduce expression of the RSV entry receptor nucleolin and inhibit viral driven cell-cell fusion. We identify a HIF regulated microRNA, miR-494, that regulates nucleolin expression. In RSV-infected mice, treatment with the clinically approved HIF prolyl-hydroxylase inhibitor, Daprodustat, reduced the level of infectious virus and infiltrating monocytes and neutrophils in the lung. This study highlights a role for HIF-signalling to limit multiple aspects of RSV infection and associated inflammation and informs future therapeutic approaches for treating this respiratory pathogen.
Essential oil terpenes may inhibit steroidogenic cytochrome P450 activities
Authors: Sharma Katyayani , Lanzilotto Angelo , Yakubu Jibira , Therkelsen Søren , Vöegel Clarissa Daniela , Toit Therina Du , Jørgensen Flemming Steen , Pandey Amit V.
Published: November 2023

Endocrine-disrupting chemicals (EDCs) may impact the development of Prostate Cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as Cytochrome P450 c17 (CYP17A1) or aromatase (CYP19A1) involved in the production of Androgens or Estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential Oils or their metabolites (EOs) like lavender oil and tea tree oil have been reported to act as potential EDCs and contribute towards sex steroid imbalance in case of prepubertal gynecomastia in boys and premature thelarche in girls due to the regular exposure to lavender-based fragrances among Hispanic population. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1 Computational docking was performed to predict the binding of EOs with CYP17A1 and CYP19A1 and functional assays were done using the radiolabeled substrates or Liquid Chromatography high-resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone & (-)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these EOs in various beauty and hygiene products is common, but only a limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output, ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for the novel compounds against hyperandrogenic disorders such as PCa and PCOS.
Structural determinants of pure antiestrogenicity
Authors: Diennet M. , Shaikh F. , El Ezzy M. , Thiombane K. , Weber S. , Poupart J. , Mendoza-Sanchez R. , Gao Z. , Gleason J. , Schuetz D.A. , Greene G. , Marinier A. , Fanning S.W. , Mader S
Published: November 2023

Inhibitory activities of antiestrogens on estrogen receptor alpha (ERα) range from mixed antagonism/agonism (selective ER modulators; SERMs) to complete antiestrogenicity associated with accelerated ERα turnover (selective ER degraders; SERDs). Here, we show using a panel of SERMs, SERDs and a PROTAC that efficient induction of ERα SUMOylation better accounts for complete transcriptional repression than increased suppression of coactivator recruitment or accelerated ERα degradation. Antiestrogen-induced ERα SUMOylation depends on the hydrophobicity of N-terminal residues of ligand binding domain (LBD) helix 12 (H12). L536 mutations, including those occurring in endocrine therapy-resistant breast cancer, abolished SUMOylation with all antiestrogens. Structures of the L536S human ERα LBD bound to fulvestrant analogs and molecular dynamics simulations predict dynamic side chain interactions with wild-type ERα H12 in the coactivator-binding groove and model the impact of L536 mutations. Together, our results show that induced SUMOylation contributes to the complete suppression of ERα activity and provide insights into its structural determinants.
Identifying cell states in single-cell RNA-seq data at statistically maximal resolution
Authors: Grobecker Pascal , van Nimwegen Erik
Published: November 2023

Single-cell RNA sequencing (scRNA-seq) has become a popular experimental method to study variation of gene expression within a population of cells. However, obtaining an accurate picture of the diversity of distinct gene expression states that are present in a given dataset is highly challenging because the sparsity of the scRNA-seq data and its inhomogeneous measurement noise properties. Although a vast number of different methods is applied in the literature for clustering cells into subsets with ‘similar’ expression profiles, these methods generally lack rigorously specified objectives, involve multiple complex layers of normalization, filtering, feature selection, dimensionalityreduction, employad hocmeasures of distance or similarity between cells, often ignore the known measurement noise properties of scRNA-seq measurements, and include a large number of tunable parameters. Consequently, it is virtually impossible to assign concrete biophysical meaning to the clusterings that result from these methods.

Here we address the following problem: Given raw unique molecule identifier (UMI) counts of an scRNA-seq dataset, partition the cells into subsets such that the gene expression states of the cells in each subset are statistically indistinguishable, and each subset corresponds to a distinct gene expression state. That is, we aim to partition cells so as to maximally reduce the complexity of the dataset without removing any of its meaningful structure. We show that, given the known measurement noise structure of scRNA-seq data, this problem is mathematically well-defined and derive its unique solution from first principles. We have implemented this solution in a tool called Cellstateswhich operates directly on the raw data and automatically determines the optimal partition and cluster number, with zero tunable parameters.

We show that, on synthetic datasets, Cellstatesalmost perfectly recovers optimal partitions. On real data, Cellstatesrobustly identifies subtle substructure within groups of cells that are traditionally annotated as a common cell type. Moreover, we show that the diversity of gene expression states that Cellstatesidentifies systematically depends on the tissue of origin and not on technical features of the experiments such as the total number of cells and total UMI count per cell. In addition to the Cellstatestool we also provide a small toolbox of software to place the identified cellstates into a hierarchical tree of higher-order clusters, to identify the most important marker genes at each branch of this hierarchy, and to visualize these results.
Autophagy regulates tumor growth and metastasis
Authors: Qiang Lei , Zhao Baozhong , Ming Mei , Wang Ning , He Tong-Chuan , Hwang Seungmin , Thorburn Andrew , He Yu-Ying
Published: November 2023

The role of autophagy in tumorigenesis and tumor metastasis remains poorly understood. Here we show that inhibition of autophagy stabilizes the transcription factor Twist1 through Sequestosome-1 (SQSTM1, also known as p62) and thus increases cell proliferation, migration, and epithelial-mesenchymal transition (EMT) in tumor development and metastasis. Inhibition of autophagy or p62 overexpression blocks Twist1 protein degradation in the proteasomes, while p62 inhibition enhances it. SQSTM1/p62 interacts with Twist1 via the UBA domain of p62, in a Twist1-ubiquitination-dependent manner. Lysine 175 in Twist1 is critical for Twist1 ubiquitination, degradation, and SQSTM1/p62 interaction. For squamous skin cancer and melanoma cells that express Twist1, SQSTM1/p62 increases tumor growth and metastasis in mice. Together, our results identified Twist1 as a key downstream protein for autophagy and suggest a critical role of the autophagy/p62/Twist1 axis in cancer development and metastasis.
Machine learning predicts metastatic progression using novel differentially expressed lncRNAs as potential markers in pancreatic cancer
Authors: Alsharoh Hasan
Published: November 2023

Abstract

Pancreatic cancer (PC) is associated with high mortality overall. Recent literature has focused on investigating long noncoding RNAs (lncRNAs) in several cancers, but studies on their functions in PC are lacking. The purpose of this study was to identify novel lncRNAs and utilize machine learning to techniques to predict metastatic cases of PC using the identified lncRNAs. To identify significantly altered expression of lncRNA in PC, data was collected from The Cancer Genome Atlas (TCGA) and RNA-sequencing (RNA-seq) transcriptomic profiles of pancreatic carcinomas were extracted for differential gene expression analysis. To assess the contribution of these lncRNAs to metastatic progression, different ML algorithms were used, including logistic regression (LR), support vector machine (SVM), random forest classifier (RFC) and eXtreme Gradient Boosting Classifier (XGBC). To improve the predictive accuracy of these models, hyperparameter tuning was performed, in addition to reducing bias through the synthetic minority oversampling technique. Out of 60,660 gene transcripts shared between 151 PC patients, 38 lncRNAs that were significantly differentially expressed were identified. To further investigate the functions of the novel lncRNAs, gene set enrichment analysis (GSEA) was performed on the population lncRNA panel. GSEA results revealed enrichment of several terms implicated in proliferation. Moreover, using the 4 ML algorithms to predict metastatic progression returned 76% accuracy for both SVM and RFC, explicitly based on the novel lncRNA panel. To the best of my knowledge, this is the first study of its kind to identify this lncRNA panel to differentiate between non-metastatic PC and metastatic PC, with many novel lncRNAs previously unmapped to PC. The ML accuracy score reveals important involvement of the detected RNAs. Based on these findings, I suggest further investigations of this lncRNA panelin vitroandin vivo, as they could be targeted for improved outcomes in PC patients, as well as assist in the diagnosis of metastatic progression based on RNA-seq data of primary pancreatic tumors.
Transcranial cortex-wide imaging of murine ischemic perfusion with large-field multifocal illumination fluorescence microscopy
Authors: Chen Zhenyue , Zhou Quanyu , Droux Jeanne , Liu Yu-Hang , Glück Chaim , Gezginer Irmak , Wyss Matthias , Yoshihara Hikari AI , Kindler Diana Rita , Weber Bruno , Wegener Susanne , El Amki Mohamad , Razansky Daniel
Published: November 2023

Ischemic stroke is a common cause of death worldwide and a main cause of morbidity. Presently, computed tomography and magnetic resonance imaging are the mainstay for stroke diagnosis and therapeutic monitoring. These modalities are often limited in terms of accessibility as well as their ability to map brain perfusion with sufficient spatial and temporal resolution, particularly in the context of preclinical studies, thus calling for development of new brain perfusion techniques featuring rapid imaging speed, cost-effectiveness, and ease of use. Herein, we report on cortex-wide perfusion imaging in murine ischemic stroke with large-field multi-focal illumination fluorescence microscopy (LMI). We attained quantitative readings of hemodynamic and structural changes in cerebral vascular network and pial vessels at capillary level resolution and 80 Hz frame rate fully transcranially. Thein vivoperfusion maps accurately delineated the ischemic core and penumbra, further exhibiting strong correlation withex vivotriphenyl tetrazolium chloride staining. Interestingly, monitoring of therapeutic effects of thrombolysis in stroke has revealed that early recanalization could effectively save the penumbra whilst reducing the infarct area. Furthermore, cross-strain comparison of perfusion dynamics affirmed that C57BL/6 mice, benefiting from more extensive pial collateral recruitment, feature a larger penumbra and smaller infarct core as compared to BALB/c mice which have few or no collaterals. Finally, we apply LMI to show that sensory stimulation-based treatment enhances blood flow and abolish perfusion deficit in the ischemic core and penumbra regions. The simple, cost-effective and minimally invasive nature of the proposed approach offers new venues for brain perfusion research under various disease conditions such as stroke, neurodegeneration or epileptic seizures.
Phylogenomic insights into the first multicellular streptophyte
Authors: Bierenbroodspot Maaike J. , Darienko Tatyana , de Vries Sophie , Fürst-Jansen Janine M.R. , Buschmann Henrik , Pröschold Thomas , Irisarri Iker , de Vries Jan
Published: November 2023

Streptophytes are best known as the clade containing the teeming diversity of embryophytes (land plants)1–4. Next to embryophytes are however a range of freshwater and terrestrial algae that bear important information on the emergence of key traits of land plants. Among these, the Klebsormidiophyceae stand out. Thriving in diverse environments—from mundane (ubiquitous occurrence on tree barks and rocks) to extreme (from the Atacama Desert to the Antarctic); Klebsormidiophyceae can exhibit filamentous body plans and display remarkable resilience as colonizers of terrestrial habitats5,6. Currently, the lack of a robust phylogenetic framework for the Klebsormidiophyceae hampers our understanding of the evolutionary history of these key traits. Here, we conducted a phylogenomic analysis utilizing advanced models that can counteract systematic biases. We sequenced 24 new transcriptomes of Klebsormidiophyceae and combined them with 14 previously published genomic and transcriptomic datasets. Using phylogenomic analysis built on 420 loci and sophisticated models, we establish a novel phylogenetic structure, dividing the six distinct genera of Klebsormidiophyceae in a novel four-order-system, with deep divergences more than 898, 765, and 734 million years ago. The reconstruction of ancestral states for habitat suggests an evolutionary history of multiple transitions between terrestrial-aquatic habitats, with Klebsormidiales having conquered land earlier than embryophytes. Focusing on the body plan of the last common ancestor of Klebsormidiophyceae, we postulate it was likely filamentous whereas the sarcinoids and unicells in Klebsormidiophyceae are likely derived states. Our data reveal that the first multicellular streptophytes likely lived more than 900 million years ago.
Computing Linkage Disequilibrium Aware Genome Embeddings using Autoencoders
Authors: Taş Gizem , Westerdijk Timo , Postma Eric ,   Project MinE ALS GWAS Consortium, Veldink Jan H. , Schönhuth Alexander , Balvert Marleen
Published: November 2023

Motivation

The completion of the human genome has paved the way for genome-wide association studies (GWAS), which have already succeeded in explaining certain proportions of heritability. GWAS are not optimally suited to detect potential non-linear effects in disease risk, possibly hidden in non-additive interactions (epistasis). Alternative methods for epistasis detection using e.g. deep neural networks are currently under active development. Despite their promise to scale to high-dimensional data, deep neural networks (DNNs) are constrained by finite computational resources, which can be rapidly depleted due to increasing complexity with the sheer size of the genome. Besides, the curse of dimensionality complicates the task of capturing meaningful genetic patterns for DNNs; therefore calls for precaution in the form of dimensionality reduction.

Results

We propose a method to compress genotyping data, involving single nucleotide polymorphisms (SNPs), while leveraging the LD structure in the genome and preserving non-linear relations among variants. This method involves clustering correlated SNPs into haplotype blocks and training per-block autoencoders that are able to learn a compressed representation of the block’s relevant genetic content. We provide an adjustable autoencoder design to accommodate diverse blocks and to bypass extensive hyperparameter tuning. We applied this method to genotyping data from Project MinE which involves a total of 23,209 ALS cases and 90,249 healthy controls. We compressed the haplotype blocks of an entire chromosome using our autoencoder-based approach, and show that this leads to more than 99% average test reconstruction accuracy - i.e. minimal information loss - while compressing the input to nearly 10% of the original size. We demonstrate that haplotype-block based autoencoders outperform their linear alternative Principal Component Analysis (PCA) by approximately 3% chromosome-wide accuracy of reconstructed variants. To the extent of our knowledge, our approach is the first to simultaneously leverage genome haplotype structure and deep neural networks for dimensionality reduction of genetic data.

Availability and Implementation

Data used in this study are available for academic use through the Project MinE Consortium athttps://www.projectmine.com/research/data-sharing/. Data accessibility is contingent upon any terms or requirements specified by the source studies. Codes for data compression are available athttps://github.com/gizem-tas/haploblock-autoencoders.
The SNARC effect involves both representation and response-selection processing stages: Evidence from ERPs
Authors: Weibin Yang , Yan Lizhu , Xiang Xinrui , Nan Weizhi
Published: November 2023

The processing stage (i.e., the early semantic representation stage, the late response-selection stage, or both) at which the spatial-numerical association of response codes (SNARC) effect occurs is still controversial. The two-stage processing model hypothesizes that the SNARC effect involves both stages and that different interference factors acting at the two stages might be the core reason for the observed stage flexibility of the SNARC effect. To test this hypothesis, the present study was designed to elicit the SNARC, Stroop (semantic-representation stage related), and Simon (response-selection stage related) effects together in one magnitude comparison task and used the event-related potentials (ERPs) to observe the temporal dynamics of these effects. The behavioral results showed no interaction between the Stroop and Simon effects, while these two effects both interacted with the SNARC effect. Furthermore, the ERP results showed an interaction of the Stroop effect with the SNARC effect for the early sensory P1 component, while the interaction of the Simon effect with the SNARC effect was evident for the late N2 and P300 components. The current study repeatedly verified the independence of Stroop and Simon effects. Most importantly, the temporal-specific interactions among the SNARC effect and the other two stage-related factors provided further evidence to support the two-stage processing model that the SNARC effect involves both the representation and response-selection stages.
Extensive loss of forage diversity in social bees due to flower constancy and communication in simulated environments
Authors: Grüter Christoph , Segers Francisca , Hayes Lucy
Published: November 2023

Bees require a diverse diet for a healthy development. Many bee species show flower constancy, that is, they visit flowers of just one species during a foraging trip. Flower constancy is important for plant reproduction, but it could impair dietary diversity in bees, especially in biodiversity-depleted, human-modified landscapes. It is assumed that flower constancy does not lower dietary diversity in social bees, such as honey bees or bumble bees, because different colony members can specialise on different plant species. However, this has never been tested. We used computer simulations to investigate the effects of flower constancy on colony diet in plant species-rich and species-poor landscapes. We also explored if communication about food sources, which is used in many social bees, further reduces forage diversity. Our simulations reveal an extensive loss of forage diversity due to flower constancy in both plant species-rich and species-poor environments. Small colonies often discovered only 30-50% of all available plant species, thereby increasing the risk of nutritional deficiencies. Our simulation results could explain why bumble bees, which have small colony sizes, are less flower constant than honey bees and stingless bees, which have larger colony sizes. Remarkably, when colonies also communicated about food sources,Simpson’s diversity, which measures the evenness of flower visits, approached near zero in plant species-poor environments. Finally, we found that food source clustering, but not habitat fragmentation impaired dietary diversity. These findings can help in the design of landscapes that increase forage diversity and improve bee nutrition and health in human-modified landscapes.
Insomnia subtypes have differentiating deviations in brain structural connectivity
Authors: Bresser T. , Blanken T.F. , de Lange S. C. , Leerssen J. , Foster-Dingley J.C. , Lakbila-Kamal O. , Wassing R. , Ramautar J.R. , Stoffers D. , van de Heuvel M.P. , van Someren E.J.W.
Published: November 2023

Objective

Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently recognized heterogeneity within the insomnia population could obscure involved brain circuits. The present study investigated whether structural brain connectivity deviations differ between recently discovered and validated insomnia subtypes.

Methods

Structural and diffusion weighted 3-Tesla MRI data of four independent studies were harmonized. The sample consisted of 73 controls without sleep complaints and 204 participants with insomnia grouped into five subtypes based on their fingerprint of personality and mood traits assessed with the Insomnia Type Questionnaire. Linear regression correcting for age, sex, and brain volume evaluated group differences in structural connectivity strength, indicated by fractional anisotropy and mean diffusivity, and evaluated within two different atlases.

Results

Insomnia subtypes showed differentiating profiles of deviating structural connectivity which moreover concentrated in different functional networks. Permutation testing against randomly drawn heterogeneous subsamples indicated significant specificity of deviation profiles in four of the five subtypes:highly distressed(p=0.019), moderately distressed reward insensitive(p=0.014), slightly distressed low reactive(p=0.006) andslightly distressed high reactive(p=0.006).

Conclusions

Our results provide a first indication that different insomnia subtypes exhibit distinct profiles of deviations in structural brain connectivity. Subtyping of insomnia could be essential for a better understanding of brain mechanisms that contribute to insomnia vulnerability.
An explainable model using Graph-Wavelet for predicting biophysical properties of proteins and measuring mutational effects
Authors: Mishra Shreya , Pandey Neetesh , Rawat Atul , Srivastava Divyanshu , Ray Arjun , Kumar Vibhor
Published: November 2023

Proteins hold multispectral patterns of different kinds of physicochemical features of amino acids in their structures, which can help understand proteins’ behavior. Here, we propose a method based on the graph-wavelet transform of signals of features of amino acids in protein residue networks derived from their structures to achieve their abstract numerical representations. Such abstract representations of protein structures hand in hand with amino-acid features can be used for different purposes, such as modelling the biophysical property of proteins. Our method outperformed graph-Fourier and convolutional neural-network-based methods in predicting the biophysical properties of proteins. Even though our method does not predict deleterious mutations, it can summarize the effect of an amino acid based on its location and neighbourhood in protein-structure using graph-wavelet to estimate its influence on the biophysical property of proteins. Such an estimate of the influence of amino-acid has the potential to explain the mechanism of the effect of deleterious non-synonymous mutations. Thus, our approach can reveal patterns of distribution of amino-acid properties in the structure of the protein in the context of a biophysical property for better classification and more insightful understanding.
MicroRNA-541-3p alters lipoproteins to reduce atherosclerosis by degrading Znf101 and Casz1 transcription factors
Authors: Ansari Abulaish , Yadav Pradeep Kumar , Zhou Liye , Prakash Binu , Gangula Bhargavi , Ijaz Laraib , Christiano Amanda , Ahmad Sameer , Rimbert Antoine , Hussain M Mahmood
Published: November 2023

High apoB-containing low-density lipoproteins (LDL) and low apoA1-containing high-density lipoproteins (HDL) are associated with atherosclerosis. In search of a molecular regulator that could simultaneously and reciprocally control both LDL and HDL levels, we screened a microRNA (miR) library using human hepatoma Huh-7 cells. We identified miR-541-3p that both decreases apoB and increases apoA1 expression by inducing mRNA degradation of two different transcription factors, Znf101 and Casz1. Znf101 enhances apoB expression while Casz1 represses apoA1 expression. The hepatic knockdown of orthologous Zfp961 and Casz1 genes in mice altered plasma lipoproteins and reduced atherosclerosis without causing hepatic lipid accumulation, most likely by lowering hepatic triglyceride production, increasing HDL cholesterol efflux capacity, and reducing lipogenesis. Notably, human genetic variants in the MIR541, ZNF101, and CASZ1 loci are significantly associated with plasma lipids and lipoprotein levels. This study identifies miR-541-3p and Znf101/Casz1 as potential therapeutic agent and targets, respectively, to reduce plasma lipoproteins and atherosclerosis without causing liver steatosis.
LARP1 senses free ribosomes to coordinate supply and demand of ribosomal proteins
Authors: Saba James A. , Huang Zixuan , Schole Kate L. , Ye Xianwen , Bhatt Shrey D. , Li Yi , Timp Winston , Cheng Jingdong , Green Rachel
Published: November 2023

Terminal oligopyrimidine motif-containing mRNAs (TOPs) encode all ribosomal proteins in mammals and are regulated to tune ribosome synthesis to cell state. Previous studies implicate LARP1 in 40S- or 80S-ribosome complexes that repress and stabilize TOPs. However, a mechanistic understanding of how LARP1 and TOPs interact with these complexes to coordinate TOP outcomes is lacking. Here, we show that LARP1 senses the cellular supply of ribosomes by directly binding non-translating ribosomal subunits. Cryo-EM structures reveal a previously uncharacterized domain of LARP1 bound to and occluding the 40S mRNA channel. Free cytosolic ribosomes induce sequestration of TOPs in repressed 80S-LARP1-TOP complexes independent of alterations in mTOR signaling. Together, this work demonstrates a general ribosome-sensing function of LARP1 that allows it to tune ribosome protein synthesis to cellular demand.

One-Sentence Summary

LARP1 directly binds free ribosomal subunits to repress TOP mRNAs
Serum Antibody Fingerprinting for SARS-CoV-2 Variants in Infected and Vaccinated Subjects by Label-Free Microarray Biosensor
Authors: Carzaniga Thomas , Casiraghi Luca , Nava Giovanni , Zanchetta Giuliano , Inzani Tommaso , Chiari Marcella , Bollati Valentina , Epis Sara , Bandi Claudio , Lai Alessia , Zehender Gianguglielmo , Bellini Tommaso , Buscaglia Marco
Published: November 2023

Both viral infection and vaccination affect the antibody repertoire of a person. Here we demonstrate that the analysis of serum antibodies carries information not only on the virus type that caused the infection, but also on the specific virus variant. We developed a rapid multiplex assay providing a fingerprint of serum antibodies against five different SARS-CoV-2 variants, based on a microarray of virus antigens immobilized on the surface of a label-free reflectometric biosensor. We analyzed serum from plasma of convalescent subjects and vaccinated volunteers and extracted individual antibody profiles of both total immunoglobulin Ig and IgA fraction. We found that Ig level profiles were strongly correlated with the specific variant of infection or vaccination and that vaccinated subjects displayed larger quantity of total Ig and lower fraction of IgA relative to the population of convalescent unvaccinated subjects.
Newborn DNA methylation age differentiates long-term weight trajectory: The Boston Birth Cohort
Authors: Meir Anat Yaskolka , Wang Guoying , Hong Xiumei , Wang Xiaobin , Liang Liming
Published: November 2023

Background

Gestational age (GEAA) estimated by newborn DNA methylation (GAmAge) is associated with maternal prenatal exposures and immediate birth outcomes. However, the association of GAmAge with long-term overweight or obesity (OWO) trajectories is yet to be determined.

Methods

GAmAge was calculated for 831 children from a US predominantly urban, low-income, multi-ethnic birth cohort using Illumina EPIC array and cord-blood DNA samples. Repeated anthropometric measurements aligned with pediatric primary care schedule allowed us to calculate body-mass-index percentiles (BMIPCT) at specific age and to define long-term weight trajectories from birth to 18 years.

Results

Four BMIPCT trajectory groups described the long-term weight trajectories: stable (consistent OWO: “early OWO”; constant normal weight: “NW”) or non-stable (OWO by year 1 of follow-up: “late OWO”; OWO by year 6 of follow-up: “NW to very late OWO”) BMIPCT. were used GAmAge was a predictor of long-term obesity, differentiating between group with consistently high BMIPCT and group with normal BMIPCT patterns and groups with late OWO development. Such differentiation can be observed in the age periods of birth to 1year, 3years, 6years, 10years, and 14years (p<0.05 for all; multivariate models adjusted for GEAA, maternal smoking, delivery method, and child’s sex). Birth weight was a mediator for the GAmAge effect on OWO status for specific groups at multiple age periods.

Conclusions

GAmAge is associated with BMI trajectories from birth to age 18 years, independent of GEAA and birth weight. If further confirmed, GAmAge may serve as an early biomarker for future OWO risk.
Understanding Reach, Effectiveness, Adoption, Implementation, and Maintenance of home-based comprehensive sexual health care: a Realist Review
Authors: Goense Cornelia J.D. , Doan Thuan-Huong P. , Kpokiri Eneyi E. , Evers Ymke J. , Estcourt Claudia S. , Crutzen Rik , Klausner Jeffrey D. , Tang Weiming , Baraitser Paula , Hoebe Christian J.P.A. , Dukers-Muijrers Nicole H.T.M.
Published: November 2023

Background

Testing forhuman immunodeficiency virus(HIV) and sexually transmitted infections (STI) is increasingly offered outside a clinic-based setting. Among key populations barriers to accessing testing and sexual health care may could be lowered due to home-based testing and care services. This review identifies which elements of home-based comprehensive sexual health care (home-based CSH) impacted which key populations, under which circumstances.

Methods

A realist review of studies focused on home-based CSH with at least self-sampling or self-testing HIV and additional sexual health care (e.g., treatment, counselling). PubMed, Embase, Cochrane Register of Controlled Trials, and PsycINFO databases were searched. Peer-reviewed quantitative and qualitative literature published between February 2012 and February 2023 was examined. The RE-AIM framework was used to systematically assess the (R) reach of key populations, (E) effectiveness of the intervention, and (AIM) effects on the adoption, implementation, and maintenance within routine sexual health care.

Results

Of 730 uniquely identified records, 92 were selected for extraction. Of these studies, 59% (54/92) reported actual interventions and 41% (38/92) described the acceptability and feasibility. Studies were mainly based in Europe or North America and were mostly targeted to MSM (59%; 55/92) (R). Overall, self-sampling or self-testing was highly acceptable across key populations. The effectiveness (E) of most studies was (expected) increased HIV testing. Adoption (A) of the home-based CSH was acceptable for care providers if linkage to care was available, even though a minority of studies reported adoption by care providers and implementation fidelity (I) of the intervention. In terms of maintenance (M), home-based CSH should be institutionalised and complementary to clinic-based sexual health care.

Conclusions

Five key findings were identified which may enhance implementation of home-based CSH. When providing the individual with a choice of testing, clear instructions, and tailored dissemination successful uptake of HIV testing may increase. For implementers perceived care and treatment benefits for clients may increase their willingness to implement home-based CSH. Therefore, home-based CSH may determine more accessible sexual health care and increased uptake of HIV testing among key populations.
Incidence and Predictors of In-stent Restenosis Following Intervention for Pulmonary Vein Stenosis due to Fibrosing Mediastinitis
Authors: Jia Mengfei , Su Hongling , Jiang Kaiyu , Wang Aqian , Guo Zhaoxia , Zhu Hai , Zhang Fu , Xin Pan , Cao Yunshan
Published: November 2023

Background

Percutaneous transluminal pulmonary venoplasty (PTPV) is an emerging treatment for pulmonary vein stenosis (PVS) caused by fibrosing mediastinitis (FM). However, the incidence and predictors of in-stent restenosis (ISR) are elusive. We sought to identify the predictors of ISR in patients with PVS caused by extraluminal compression due to FM.

Methods

We retrospectively enrolled patients with PVS-FM who underwent PTPV between July 1, 2018, and December 31, 2022. According to ISR status, patients were divided into two groups: the ISR group and the non-ISR group. Baseline characteristics (demographics and lesions) and procedure-related information were abstracted from patient records and analyzed. Univariate and multivariate analyses were performed to determine the predictors of ISR.

Results

A total of 142 stents were implanted in 134 PVs of 65 patients with PVS-FM. Over a median follow-up of 6.6 (3.4-15.7) months, 61 of 134 PVs suffered from ISR. Multivariate analysis demonstrated a significantly lower risk of ISR in PVs with a larger reference vessel diameter (RVD) (odds ratio (OR): 0.79; 95% confidence interval [CI]: 0.64 to 0.98;P=0.032), and stenosis of the corresponding pulmonary artery (Cor-PA) independently increased the risk of restenosis (OR: 3.41; 95% CI: 1.31 to 8.86;P=0.012). The cumulative ISR was 6.3%, 21.4%, and 39.2% at the 3-, 6-, and 12-month follow-ups, respectively.

Conclusion

ISR is very high in PVS-FM, which is independently associated with RVD and Cor-PA stenosis.

Central illustration

Based on the constructed prediction model, the RVD and stenosis of Cor-PA were found to be independently associated with ISR, and their sensitivity and optimal cutoff values for the prediction of restenosis are shown in (a) and (b), respectively. The risk of ISR significantly increased when PA stenosis occurred; the risk of restenosis decreased significantly when the RVD was larger than 8.4 mm.
Identification of novel tail-anchored membrane proteins integrated by the bacterial twin-arginine translocase
Authors: Gallego-Parrilla José Jesús , Severi Emmanuele , Chandra Govind , Palmer Tracy
Published: November 2023

The twin arginine protein transport (Tat) system exports folded proteins across the cytoplasmic membranes of prokaryotes and the energy transducing membranes of plant thylakoids and mitochondria. Proteins are targeted to the Tat machinery by N-terminal signal peptides with a conserved twin arginine motif, and some substrates are exported as heterodimers where the signal peptide is present on one of the partner proteins. A subset of Tat substrates is found in the membrane. Tat-dependent membrane proteins usually have large globular domains and a single transmembrane helix present at the N- or C-terminus. Five Tat substrates that have C-terminal transmembrane helices have previously been characterised in the model bacteriumEscherichia coli. Each of these is an iron-sulphur cluster-containing protein involved in electron transfer from hydrogen or formate. Here we have undertaken a bioinformatic search to identify further tail-anchored Tat substrates encoded in bacterial genomes. Our analysis has revealed additional tail-anchored iron-sulphur proteins associated in modules with either ab-type cytochrome or a quinol oxidase. We also identified further candidate tail-anchored Tat substrates, particularly among members of the actinobacterial genus, that are not predicted to contain cofactors. Using reporter assays we show experimentally that six of these have both N-terminal Tat signal peptides and C-terminal transmembrane helices. The newly-identified proteins include a carboxypeptidase and a predicted protease, and four sortase substrates for which membrane integration is a pre-requisite for covalent attachment to the cell wall.
Association cortical areas in the mouse contain a large population of fast-spiking GABAergic neurons that do not express parvalbumin
Authors: Courcelles Erik Justin , Kjelsberg Kasper , Convertino Laura , Nair Rajeevkumar Raveendran , Witter Menno P. , Nigro Maximiliano José
Published: November 2023

GABAergic neurons represent 10-15% of the neuronal population of the cortex but exert a powerful control over information flow in cortical circuits. The largest GABAergic class in the neocortex is represented by the parvalbumin-expressing (PV-INs) fast-spiking neurons, which provide powerful somatic inhibition to their postsynaptic targets. Recently, the density of PV-INs has been shown to be lower in associative areas of the mouse cortex as compared to sensory and motor areas. Modeling work based on these quantifications linked the low-density of PV-INs with specific computations of associative cortices. However, it is still unknown whether the total GABAergic population of association cortices is smaller or whether another GABAergic type can compensate for the low density of PV-INs. In the present study we investigated these hypotheses using a combination of neuroanatomy, mouse genetics and neurophysiology. We found that the GABAergic population of association areas is comparable to that of primary sensory areas, and it is enriched of fast-spiking neurons that do not express PV and were not accounted for by previous quantifications. We developed an intersectional viral strategy to demonstrate that the synaptic output of fast-spiking neurons is comparable across cortical regions. Our results provide quantifications of the density and output strength of fast-spiking GABAergic neurons and offers new biological constrains to refine current models of cortical computations.
Apobec-Mediated Retroviral HypermutationIn Vivois Dependent on Mouse Strain
Authors: Byun Hyewon , Singh Gurvani B. , Xu Wendy Kaichun , Das Poulami , Reyes Alejandro , Battenhouse Anna , Wylie Dennis C. , Lozano Mary M. , Dudley Jaquelin P.
Published: November 2023

Replication of the complex retrovirus mouse mammary tumor virus (MMTV) is antagonized by murine Apobec3 (mA3), a member of the Apobec family of cytidine deaminases. We have shown that MMTV-encoded Rem protein inhibits proviral mutagenesis by the Apobec enzyme, activation-induced cytidine deaminase (AID) during viral replication in BALB/c mice. To further study the role of Remin vivo, we have infected C57BL/6 (B6) mice with a superantigen-independent lymphomagenic strain of MMTV (TBLV-WT) or a mutant strain (TBLV-SD) that is defective in Rem and its cleavage product Rem-CT. Unlike MMTV, TBLV induced T-cell tumors in µMT mice, indicating that mature B cells, which express the highest AID levels, are not required for TBLV replication. Compared to BALB/c, B6 mice were more susceptible to TBLV infection and tumorigenesis. The lack of Rem expression accelerated B6 tumorigenesis at limiting doses compared to TBLV-WT in either wild-type B6 or AID-deficient mice. However, unlike proviruses from BALB/c mice, high-throughput sequencing indicated that proviral G-to-A or C-to-T changes did not significantly differ in the presence and absence of Rem expression.Ex vivostimulation showed higher levels of mA3 relative to AID in B6 compared to BALB/c splenocytes, but effects of agonists differed in the two strains. RNA-Seq revealed increased transcripts related to growth factor and cytokine signaling in TBLV-SD-induced tumors relative to those from TBLV-WT, consistent with a third Rem function. Thus, Rem-mediated effects on tumorigenesis in B6 mice are independent of Apobec-mediated proviral hypermutation.