bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome profiling of Nudix hydrolase gene deletions in the thermoacidophilic archaeon Sulfolobus acidocaldarius
Authors: Breuer Ruth , Gomes-Filho José Vicente , Yuan Jing , Randau Lennart
Published: June 2023

Nudix hydrolases comprise a large and ubiquitous protein superfamily that catalyzes the hydrolysis of a nucleoside diphosphate linked to another moiety X (Nudix). Sulfolobus acidocaldarius possesses four Nudix domain-containing proteins (SACI_RS00730/Saci_0153, SACI_RS02625/Saci_0550, SACI_RS00060/Saci_0013/Saci_NudT5, and SACI_RS00575/Saci_0121). Deletion strains were generated for the four individual Nudix genes and for both Nudix genes annotated to encode ADP-ribose pyrophosphatases (SACI_RS00730, SACI_RS00060) and did not reveal a distinct phenotype compared to the wild-type strain under standard growth conditions, nutrient stress or heat stress conditions. We employed RNA-seq to establish the transcriptome profiles of the Nudix deletion strains, revealing a large number of differentially regulated genes, most notably in the ΔSACI_RS00730/SACI_RS00060 double knock-out strain and the ΔSACI_RS00575 single deletion strain. The absence of Nudix hydrolases is suggested to impact transcription via differentially regulated transcriptional regulators. We observed downregulation of the lysine biosynthesis and the archaellum formation iModulons in stationary phase cells, as well as upregulation of two genes involved in the de novo NAD+ biosynthesis pathway. Furthermore, the deletion strains exhibited upregulation of two thermosome subunits (α, β) and the toxin-antitoxin system VapBC, which are implicated in the archaeal heat shock response. These results uncover a defined set of pathways that involve archaeal Nudix protein activities and assist in their functional characterization.
Evolutionary dynamics of plastomes in coscinodiscophycean diatoms revealed by comparative genomics
Authors: Liu Feng , Wang Yichao , Huang Hailong , Chen Nansheng
Published: June 2023

To understand the evolution of coscinodiscophycean diatoms, plastome sequences of six coscinodiscophycean diatom species were constructed and analyzed in this study, doubling the number of constructed plastome sequences in Coscinodiscophyceae (radial centrics). The platome sizes varied substantially in Coscinodiscophyceae, ranging from 119.1 kb of Actinocyclus subtilis to 135.8 kb of Stephanopyxis turris. Plastomes in Paraliales and Stephanopyxales tended to be larger than those in Rhizosoleniales and Coscinodiacales, which were due to the expansion of the inverted repeats (IRs) and to the marked increase of the large single copy (LSC). Phylogenomic analysis indicated that Paralia and Stephanopyxis clustered tightly to form the Paraliales-Stephanopyxales complex, which was sister to the Rhizosoleniales-Coscinodiscales complex. The divergence time between Paraliales and Stephanopyxales was estimated at 85 MYA in the middle Upper Cretaceous, indicating that Paraliales and Stephanopyxales appeared later than Coscinodiacales and Rhizosoleniales according to their phylogenetic relationships. Frequent losses of housekeeping protein-coding genes (PCGs) were observed in these coscinodiscophycean plastomes, indicating that diatom plastomes showed an ongoing reduction in gene content during evolution. Two acpP genes (acpP1 and acpP2) detected in diatom plastomes were found to be originated from an early gene duplication event occurred in the common progenitor after diatom emergence, rather than multiple independent gene duplications occurring in different lineages of diatoms. The IRs in Stephanopyxis turris and Rhizosolenia fallax-imbricata exhibited a similar trend of large expansion to the small single copy (SSC) and slightly small contraction from the LSC, which eventually led to the conspicuous increase in IR size. Gene order was highly conserved in Coscinodiacales, while multiple rearrangements were observed in Rhizosoleniales and between Paraliales and Stephanopyxales. Our results greatly expanded the phylogenetic breadth in Coscinodiscophyceae and gained novel insights into the evolution of plastomes in diatoms.
Genetic characteristics of waterfowl-origin H5N6 highly pathogenic avian influenza viruses and their pathogenesis in ducks and chickens
Authors: He Zhuoliang , Wang Xia , Lin Yu , Feng Siyu , Huang Xinyu , Zhao Luxiang , Zhang Junsheng , Ding Yangbao , Li Weiqiang , Yuan Runyu , Jiao Peirong
Published: June 2023

Waterfowl, such as ducks, are natural hosts for avian influenza viruses (AIVs) and act as a bridge for transmitting the virus to humans or susceptible chickens. Since 2013, chickens and ducks have been threatened by waterfowl-origin H5N6 subtype AIVs in China. Therefore, it is necessary to investigate the genetic evolution, transmission, and pathogenicity of these viruses. In this study, we determined the genetic characteristics, transmission, and pathogenicity of waterfowl-origin H5N6 viruses in southern China. The hemagglutinin (HA) genes of H5N6 viruses were classified into the MIX-like branch of clade 2.3.4.4h. The neuraminidase (NA) genes belonged to the Eurasian lineage. The PB1 genes were classified into MIX-like and VN 2014-like branches. The remaining five genes were clustered into the MIX-like branch. Therefore, these viruses belonged to different genotypes. The cleavage site of the HA proteins of these viruses was RERRRKR/G, a molecular characteristic of the H5 highly pathogenic AIV. The NA stalk of all H5N6 viruses contained 11 amino acid deletions at residues 58–68. All viruses contained 627E and 701D in the PB2 proteins, which were molecular characteristics of typical bird AIVs. Furthermore, this study showed that Q135 and S23 viruses could replicate systematically in chickens and ducks. They did not cause death in ducks but induced mild clinical signs in them. All the infected chickens showed severe clinical signs and died. These viruses were shed from the digestive and respiratory tracts and transmitted horizontally in chickens and ducks. Our results provide valuable information for preventing H5N6 avian influenza outbreaks.
Glycan-related genes in human gut microbiota exhibit differential distribution and diversity in carbohydrate degradation and glycan synthesis
Authors: Takihara Hayato , Okuda Shujiro
Published: June 2023

Interactions between humans and the gut microbiome occur by supplying nutrients to gut epithelial cells via short-chain fatty acids obtained from dietary carbohydrates or mucins and activating immunity via mucins’ degradation. The degradation of carbohydrates derived from food is an important function for organisms to obtain energy. However, since humans possess only 17 genes encoding carbohydrate-degrading enzymes, the gut microbiome is responsible for degrading plant-derived polysaccharides. Using the method for extracting glycan-related genes from the metagenomes constructed thus far, we calculated the distribution and abundance of different glycan-related genes in the healthy human gut metagenome. Glycan-related genes showed an abundance of 0.64–11.00, indicating large individual differences. However, the distribution of the classes of glycan-related genes was similar between the samples. In addition, the function of carbohydrate degradation was divided into three clusters, showing high diversity; however, the synthesis function was not divided, indicating low diversity. The substrates of enzymes for carbohydrate degradation between clusters were either plant-derived polysaccharides or biased toward degrading polysaccharides derived from other sources. These functional biases differ depending on the type of microorganism used. Based on these findings, we predicted that 1) diversity will be constant because the influence on the host by the transferase of gut bacteria is a function derived from the genome, and 2) diversity will be high because the influence on the host by the hydrolase of gut bacteria is affected by incoming dietary carbohydrates.
Development and validation of an interpretable machine learning model—Predicting mild cognitive impairment in a high-risk stroke population
Authors: Yan Feng-Juan , Chen Xie-Hui , Quan Xiao-Qing , Wang Li-Li , Wei Xin-Yi , Zhu Jia-Liang
Published: June 2023

Background

Mild cognitive impairment (MCI) is considered a preclinical stage of Alzheimer’s disease (AD). People with MCI have a higher risk of developing dementia than healthy people. As one of the risk factors for MCI, stroke has been actively treated and intervened. Therefore, selecting the high-risk population of stroke as the research object and discovering the risk factors of MCI as early as possible can prevent the occurrence of MCI more effectively.

Methods

The Boruta algorithm was used to screen variables, and eight machine learning models were established and evaluated. The best performing models were used to assess variable importance and build an online risk calculator. Shapley additive explanation is used to explain the model.

Results

A total of 199 patients were included in the study, 99 of whom were male. Transient ischemic attack (TIA), homocysteine, education, hematocrit (HCT), diabetes, hemoglobin, red blood cells (RBC), hypertension, prothrombin time (PT) were selected by Boruta algorithm. Logistic regression (AUC = 0.8595) was the best model for predicting MCI in high-risk groups of stroke, followed by elastic network (ENET) (AUC = 0.8312), multilayer perceptron (MLP) (AUC = 0.7908), extreme gradient boosting (XGBoost) (AUC = 0.7691), and support vector machine (SVM) (AUC = 0.7527), random forest (RF) (AUC = 0.7451), K-nearest neighbors (KNN) (AUC = 0.7380), decision tree (DT) (AUC = 0.6972). The importance of variables suggests that TIA, diabetes, education, and hypertension are the top four variables of importance.

Conclusion

Transient ischemic attack (TIA), diabetes, education, and hypertension are the most important risk factors for MCI in high-risk groups of stroke, and early intervention should be performed to reduce the occurrence of MCI.
Comprehensive transcript-level analysis reveals transcriptional reprogramming during the progression of Alzheimer’s disease
Authors: Wu Hao , Wang Jiao , Hu Xiaoyuan , Zhuang Cheng , Zhou Jianxin , Wu Peiru , Li Shengli , Zhao Robert Chunhua
Published: June 2023

Background

Alzheimer’s disease (AD) is a common neurodegenerative disorder that has a multi-step disease progression. Differences between moderate and advanced stages of AD have not yet been fully characterized.

Materials and methods

Herein, we performed a transcript-resolution analysis in 454 AD-related samples, including 145 non-demented control, 140 asymptomatic AD (AsymAD), and 169 AD samples. We comparatively characterized the transcriptome dysregulation in AsymAD and AD samples at transcript level.

Results

We identified 4,056 and 1,200 differentially spliced alternative splicing events (ASEs) that might play roles in the disease progression of AsymAD and AD, respectively. Our further analysis revealed 287 and 222 isoform switching events in AsymAD and AD, respectively. In particular, a total of 163 and 119 transcripts showed increased usage, while 124 and 103 transcripts exhibited decreased usage in AsymAD and AD, respectively. For example, gene APOA2 showed no expression changes between AD and non-demented control samples, but expressed higher proportion of transcript ENST00000367990.3 and lower proportion of transcript ENST00000463812.1 in AD compared to non-demented control samples. Furthermore, we constructed RNA binding protein (RBP)-ASE regulatory networks to reveal potential RBP-mediated isoform switch in AsymAD and AD.

Conclusion

In summary, our study provided transcript-resolution insights into the transcriptome disturbance of AsymAD and AD, which will promote the discovery of early diagnosis biomarkers and the development of new therapeutic strategies for patients with AD.
An olfactory-based Brain-Computer Interface: electroencephalography changes during odor perception and discrimination
Authors: Morozova Marina , Bikbavova Alsu , Bulanov Vladimir , Lebedev Mikhail A.
Published: June 2023

Brain-Computer Interfaces (BCIs) are devices designed for establishing communication between the central nervous system and a computer. The communication can occur through different sensory modalities, and most commonly visual and auditory modalities are used. Here we propose that BCIs can be expanded by the incorporation of olfaction and discuss the potential applications of such olfactory BCIs. To substantiate this idea, we present results from two olfactory tasks: one that required attentive perception of odors without any overt report, and the second one where participants discriminated consecutively presented odors. In these experiments, EEG recordings were conducted in healthy participants while they performed the tasks guided by computer-generated verbal instructions. We emphasize the importance of relating EEG modulations to the breath cycle to improve the performance of an olfactory-based BCI. Furthermore, theta-activity could be used for olfactory-BCI decoding. In our experiments, we observed modulations of theta activity over the frontal EEG leads approximately 2 s after the inhalation of an odor. Overall, frontal theta rhythms and other types of EEG activity could be incorporated in the olfactory-based BCIs which utilize odors either as inputs or outputs. These BCIs could improve olfactory training required for conditions like anosmia and hyposmia, and mild cognitive impairment.
Robust and efficient representations of dynamic stimuli in hierarchical neural networks via temporal smoothing
Authors: Sihn Duho , Kwon Oh-Sang , Kim Sung-Phil
Published: June 2023

Introduction

Efficient coding that minimizes informational redundancy of neural representations is a widely accepted neural coding principle. Despite the benefit, maximizing efficiency in neural coding can make neural representation vulnerable to random noise. One way to achieve robustness against random noise is smoothening neural responses. However, it is not clear whether the smoothness of neural responses can hold robust neural representations when dynamic stimuli are processed through a hierarchical brain structure, in which not only random noise but also systematic error due to temporal lag can be induced.

Methods

In the present study, we showed that smoothness via spatio-temporally efficient coding can achieve both efficiency and robustness by effectively dealing with noise and neural delay in the visual hierarchy when processing dynamic visual stimuli.

Results

The simulation results demonstrated that a hierarchical neural network whose bidirectional synaptic connections were learned through spatio-temporally efficient coding with natural scenes could elicit neural responses to visual moving bars similar to those to static bars with the identical position and orientation, indicating robust neural responses against erroneous neural information. It implies that spatio-temporally efficient coding preserves the structure of visual environments locally in the neural responses of hierarchical structures.

Discussion

The present results suggest the importance of a balance between efficiency and robustness in neural coding for visual processing of dynamic stimuli across hierarchical brain structures.
Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases – a retrospective cross-sectional study
Authors: Brauchle Felix , Rapp Daniel , Senel Makbule , Huss André , Dreyhaupt Jens , Klose Veronika , Süße Marie , Stürner Klarissa Hanja , Leypoldt Frank , Tumani Hayrettin , Lewerenz Jan
Published: June 2023

Introduction

The polyspecific intrathecal immune response (PSIIR), aka MRZ reaction (M = measles, R = rubella, Z = zoster, optionally Herpes simplex virus, HSV) is defined as intrathecal immunoglobulin synthesis (IIS) for two or more unrelated viruses. Although an established cerebrospinal fluid (CSF) biomarker for multiple sclerosis (MS), a chronic autoimmune-inflammatory neurological disease (CAIND) of the central nervous system (CNS) usually starting in young adulthood, the full spectrum of CAINDs with a positive PSIIR remains ill defined.

Methods

In this retrospective, cross-sectional study, patients with CSF-positive oligoclonal bands (OCB) and - to enrich for non-MS diagnoses - aged ≥50 years were enrolled.

Results

Of 415 with PSIIR testing results (MRZ, HSV optional), 76 were PSIIR-positive. Of these, 25 (33%) did not meet the diagnostic criteria for MS spectrum diseases (MS-S) comprising clinically or radiologically isolated syndrome (CIS/RIS) or MS. PSIIR-positive non-MS-S phenotypes were heterogenous with CNS, peripheral nerve and motor neuron involvement and often defied unequivocal diagnostic classification. A rating by neuroimmunology experts suggested non-MS CAINDs in 16/25 (64%). Long-term follow-up available in 13 always showed a chronically progressive course. Four of five responded to immunotherapy. Compared to MS-S patients, non-MS CAIND patients showed less frequent CNS regions with demyelination (25% vs. 75%) and quantitative IgG IIS (31% vs. 81%). MRZ-specific IIS did not differ between both groups, while additional HSV-specific IIS was characteristic for non-MS CAIND patients.

Discussion

In conclusion, PSIIR positivity occurs frequently in non-MS-S patients ≥50 years. Although sometimes apparently coincidental, the PSIIR seems to represent a suitable biomarker for previously unnoticed chronic neurologic autoimmunities, which require further characterization.
Emergent structural and functional properties of hippocampal multi-cellular aggregates
Authors: Acero Victor P. , Das Suradip , Rivellini Olivia , Purvis Erin M. , Adewole Dayo O. , Cullen Daniel Kacy
Published: June 2023

Hippocampal neural networks are distinctly capable of integrating multi-modal sensory inputs to drive memory formation. Neuroscientific investigations using simplified in vitro models have greatly relied on planar (2D) neuronal cultures made from dissociated tissue. While these models have served as simple, cost-effective, and high-throughput tools for examining various morphological and electrophysiological characteristics of hippocampal networks, 2D cultures fail to reconstitute critical elements of the brain microenvironment that may be necessary for the emergence of sophisticated integrative network properties. To address this, we utilized a forced aggregation technique to generate high-density (>100,000 cells/mm3) multi-cellular three-dimensional aggregates using rodent embryonic hippocampal tissue. We contrasted the emergent structural and functional properties of aggregated (3D) and dissociated (2D) cultures over 28 days in vitro (DIV). Hippocampal aggregates displayed robust axonal fasciculation across large distances and significant neuronal polarization, i.e., spatial segregation of dendrites and axons, at earlier time points compared to dissociated cultures. Moreover, we found that astrocytes in aggregate cultures self-organized into non-overlapping quasi-domains and developed highly stellate morphologies resembling astrocyte structures in vivo. We maintained cultures on multi-electrode arrays (MEAs) to assess spontaneous electrophysiological activity for up to 28 DIV. We found that 3D networks of aggregated cultures developed highly synchronized networks and with high burstiness by 28 DIV. We also demonstrated that dual-aggregate networks became active by 7 DIV, in contrast to single-aggregate networks which became active and developed synchronous bursting activity with repeating motifs by 14 DIV. Taken together, our findings demonstrate that the high-density, multi-cellular, 3D microenvironment of hippocampal aggregates supports the recapitulation of emergent biofidelic morphological and functional properties. Our findings suggest that neural aggregates may be used as segregated, modular building blocks for the development of complex, multi-nodal neural network topologies.
Oscillatory neural network learning for pattern recognition: an on-chip learning perspective and implementation
Authors: Abernot Madeleine , Azemard Nadine , Todri-Sanial Aida
Published: June 2023

In the human brain, learning is continuous, while currently in AI, learning algorithms are pre-trained, making the model non-evolutive and predetermined. However, even in AI models, environment and input data change over time. Thus, there is a need to study continual learning algorithms. In particular, there is a need to investigate how to implement such continual learning algorithms on-chip. In this work, we focus on Oscillatory Neural Networks (ONNs), a neuromorphic computing paradigm performing auto-associative memory tasks, like Hopfield Neural Networks (HNNs). We study the adaptability of the HNN unsupervised learning rules to on-chip learning with ONN. In addition, we propose a first solution to implement unsupervised on-chip learning using a digital ONN design. We show that the architecture enables efficient ONN on-chip learning with Hebbian and Storkey learning rules in hundreds of microseconds for networks with up to 35 fully-connected digital oscillators.
Toward reproducible models of sequence learning: replication and analysis of a modular spiking network with reward-based learning
Authors: Zajzon Barna , Duarte Renato , Morrison Abigail
Published: June 2023

To acquire statistical regularities from the world, the brain must reliably process, and learn from, spatio-temporally structured information. Although an increasing number of computational models have attempted to explain how such sequence learning may be implemented in the neural hardware, many remain limited in functionality or lack biophysical plausibility. If we are to harvest the knowledge within these models and arrive at a deeper mechanistic understanding of sequential processing in cortical circuits, it is critical that the models and their findings are accessible, reproducible, and quantitatively comparable. Here we illustrate the importance of these aspects by providing a thorough investigation of a recently proposed sequence learning model. We re-implement the modular columnar architecture and reward-based learning rule in the open-source NEST simulator, and successfully replicate the main findings of the original study. Building on these, we perform an in-depth analysis of the model's robustness to parameter settings and underlying assumptions, highlighting its strengths and weaknesses. We demonstrate a limitation of the model consisting in the hard-wiring of the sequence order in the connectivity patterns, and suggest possible solutions. Finally, we show that the core functionality of the model is retained under more biologically-plausible constraints.
Exploring healthy and climate-friendly diets for Danish adults: an optimization study using quadratic programming
Authors: Nordman Matilda , Lassen Anne Dahl , Stockmarr Anders , van ‘t Veer Pieter , Biesbroek Sander , Trolle Ellen
Published: June 2023

Background

A transition to healthy and sustainable diets has the potential to improve human and planetary health but diets need to meet requirements for nutritional adequacy, health, environmental targets, and be acceptable to consumers.

Objective

The objective of this study was to derive a nutritionally adequate and healthy diet that has the least deviation possible from the average observed diet of Danish adults while aiming for a greenhouse gas emission (GHGE) reduction of 31%, corresponding to the GHGE level of the Danish plant-rich diet, which lays the foundation for the current healthy and sustainable food-based dietary guidelines (FBDGs) in Denmark.

Methods

With an objective function minimizing the departure from the average observed diet of Danish adults, four diet optimizations were run using quadratic programming, with different combinations of diet constraints: (1) nutrients only (Nutri), (2) nutrients and health-based targets for food amounts (NutriHealth), (3) GHGE only (GHGE), and finally, (4) combined nutrient, health and GHGE constraints (NutriHealthGHGE).

Results

The GHGE of the four optimized diets were 3.93 kg CO2-eq (Nutri), 3.77 kg CO2-eq (NutriHealth) and 3.01 kg CO2-eq (GHGE and NutriHealthGHGE), compared to 4.37 kg CO2-eq in the observed diet. The proportion of energy from animal-based foods was 21%–25% in the optimized diets compared to 34% in the observed diet and 18% in the Danish plant-rich diet. Moreover, compared to the average Danish diet, the NutriHealthGHGE diet contained more grains and starches (44 E% vs. 28 E%), nuts (+230%), fatty fish (+89%), eggs (+47%); less cheese (−73%), animal-based fats (−76%), total meat (−42%); and very limited amounts of ruminant meat, soft drinks, and alcoholic beverages (all-90%), while the amounts of legumes and seeds were unchanged. On average, the mathematically optimized NutriHealthGHGE diet showed a smaller deviation from the average Danish diet compared to the Danish plant-rich diet (38% vs. 169%, respectively).

Conclusion

The final optimized diet presented in this study represents an alternative way of composing a nutritionally adequate and healthy diet that has the same estimated GHGE as a diet consistent with the climate-friendly FBDGs in Denmark. As this optimized diet may be more acceptable for some consumers, it might help to facilitate the transition toward more healthy and sustainable diets in the Danish population.
Identification of co-regulated genes associated with doxorubicin resistance in the MCF-7/ADR cancer cell line
Authors: Miri Ali , Gharechahi Javad , Samiei Mosleh Iman , Sharifi Kazem , Jajarmi Vahid
Published: June 2023

Introduction

The molecular mechanism of chemotherapy resistance in breast cancer is not well understood. The identification of genes associated with chemoresistance is critical for a better understanding of the molecular processes driving resistance.

Methods

This study used a co-expression network analysis of Adriamycin (or doxorubicin)-resistant MCF-7 (MCF-7/ADR) and its parent MCF-7 cell lines to explore the mechanisms of drug resistance in breast cancer. Genes associated with doxorubicin resistance were extracted from two microarray datasets (GSE24460 and GSE76540) obtained from the Gene Expression Omnibus (GEO) database using the GEO2R web tool. The candidate differentially expressed genes (DEGs) with the highest degree and/or betweenness in the co-expression network were selected for further analysis. The expression of major DEGs was validated experimentally using qRT–PCR.

Results

We identified twelve DEGs in MCF-7/ADR compared with its parent MCF-7 cell line, including 10 upregulated and 2 downregulated DEGs. Functional enrichment suggests a key role for RNA binding by IGF2BPs and epithelial-to-mesenchymal transition pathways in drug resistance in breast cancer.

Discussion

Our findings suggested that MMP1, VIM, CNN3, LDHB, NEFH, PLS3, AKAP12, TCEAL2, and ABCB1 genes play an important role in doxorubicin resistance and could be targeted for developing novel therapies by chemical synthesis approaches.
A model-based head-to-head comparison of single-agent lurbinectedin in the pivotal ATLANTIS Study
Authors: Fudio Salvador , Pérez-Ramos Laura , Asín-Prieto Eduardo , Zeaiter Ali , Lubomirov Rubin
Published: June 2023

Introduction

Lurbinectedin is a selective inhibitor of oncogenic transcription U.S. Food and Drug Administration (FDA)-approved for patients with relapsed small cell lung cancer (SCLC) as monotherapy at 3.2 mg/m2 every 3 weeks (q3wk). ATLANTIS was a phase 3 study in SCLC with lurbinectedin 2.0 mg/m2 plus doxorubicin 40 mg/m2 q3wk vs physician’s choice, with overall survival (OS) as the primary endpoint and objective response rate (ORR) as the secondary endpoint. This work aimed to dissect the contribution of lurbinectedin and doxorubicin to antitumor effects in SCLC, and to predict the efficacy of single-agent lurbinectedin at 3.2 mg/m2 in ATLANTIS to allow for a head-to-head comparison with the control arm.

Methods

The dataset included exposure and efficacy data from 387 patients with relapsed SCLC (ATLANTIS, n=288; study B-005, n=99). Patients in the ATLANTIS control arm (n=289) were used for comparison. Unbound plasma lurbinectedin area under the concentration-time curve (AUCu) and total plasma doxorubicin area under the concentration-time curve (AUCDOX) were used as exposure metrics. Univariate and multivariate analyses were conducted to determine the best predictors and predictive model for OS and ORR. OS baseline hazard was best described by a log-logistic distribution, with chemotherapy-free interval (CTFI), lactate dehydrogenase, albumin, brain metastases, neutrophils/lymphocytes ratio, AUCu, and the interaction between AUCu and AUCDOX as predictors. Effect of AUCu on ORR best fitted to a sigmoid-maximal response (Emax) logistic model, where Emax was dependent on CTFI.

Results

Head-to-head comparisons with predicted 3.2 mg/m2 lurbinectedin resulted in a positive outcome in ATLANTIS, with hazard ratio (95% prediction intervals [95% PI]) for OS of 0.54 (0.41, 0.72), and odds ratio (95% PI) for ORR of 0.35 (0.25, 0.5).

Conclusion

These results support the superiority of lurbinectedin monotherapy for relapsed SCLC over other approved therapies.
Development and validation of cancer-associated fibroblasts-related gene landscape in prognosis and immune microenvironment of bladder cancer
Authors: Zhang Meng , Zhu Junlong , Zhang Pan , Li Lingxun , Min Min , Li Tinghao , He Weiyang
Published: June 2023

Backgrounds

Bladder cancer (BLCA) is one of the most prevalent cancers of the genitourinary system, the clinical outcomes of patients with BLCA are bad, and the morbidity rate is high. One of the key components of the tumor microenvironment (TME) is cancer-associated fibroblasts (CAFs) which are critically involved in BLCA tumorigenesis. Previous studies have shown the involvement of CAFs in tumor growth, cancer progression, immune evasion, angiogenesis, and chemoresistance in several cancers such as breast, colon, pancreatic, ovarian, and prostate cancers. However, only a few studies have shown the role of CAFs in the occurrence and development of BLCA.

Methods

We have retrieved and merged the data on RNA-sequencing of patients with BLCA from databases including “the Cancer Genome Atlas” and “Gene Expression Omnibus.” Next, we compared the differences in CAFs-related genes (CRGs) expression between normal and BLCA tissues. Based on CRGs expression, we randomly divided patients into two groups. Next, we determined the correlation between CAFs subtypes and differentially expressed CRGs (DECRGs) between the two subtypes. Furthermore, the “Gene Ontology” and “Kyoto Encyclopedia of Genes and Genomes pathway” enrichment analyses were conducted to determine the functional characteristics between the DECRGs and clinicopathology.

Results

We identified five genes (POF1B, ARMCX1, ALDOC, C19orf33, and KRT13) using multivariate COX regression and “Least Absolute Shrinkage and Selection Operator (LASSO) COX regression analysis” for developing a prognostic model and calculating the CRGs-risk score. The TME, mutation, CSC index, and drug sensitivity were also analyzed.

Conclusion

We constructed a novel five- CRGs prognostic model, which sheds light on the roles of CAFs in BLCA.
Characteristics of patients who use yoga for pain management in Indian yoga and naturopathy settings: a retrospective review of electronic medical records
Authors: Nair Pradeep M. K. , Kriplani Sucheta , Kodali Prakash Babu , Maheshwari Ayush , Bhalavat Kinjal Dilipsinh , Singh Deepika , Saini Sanjeev , Yadav Dinesh , Keswani Jyoti , Silwal Karishma , Sharma Hemanshu , Tewani Gulab Rai
Published: June 2023

Objectives

The aim of this study is to identify the characteristics of patients who underwent yoga therapy for pain in yoga and naturopathy clinical settings in India.

Methods

Electronic medical records of patients who received yoga therapy for pain in three inpatient yoga and naturopathy hospitals were reviewed retrospectively from January 2021 to September 2022. Demographic characteristics and details on pain condition, socioeconomic status, comorbidities, ancillary therapies received, and insurance status were collected. In addition, we prospectively collected data on adherence to yoga practice through a telephonic interview.

Results

A total of 984 patients were identified from a pool of 3,164 patients who received yoga therapy for pain for an average of 9.48 (1.13) days. Patients aged between 8 and 80 underwent therapy for varying pain conditions and diseases that include pain in the extremities, pain due to infection, trauma, degenerative diseases, autoimmune diseases, and spine and neurological diseases. The majority of the patients were females (66.3%), from middle class families (74.8%), and who did not have any insurance coverage (93.8%). Most of the patients were under naturopathy treatment (99.8%), followed by ayurveda (56%), and physiotherapy (49.3%), along with yoga therapy. All patients reported a significant reduction in pain post-integrated yoga therapy (p < 0.001). Adherence to yoga was significantly associated with underlying pain conditions, the presence of comorbidities, the types of therapies used, and socioeconomic status (p < 0.001).

Conclusion

This study highlights the real-time application of yoga in pain management in Indian yoga and naturopathy settings, as well as implications for future research.
Non-pharmacologic approaches to treatment of pediatric functional abdominal pain disorders
Authors: Chakraborty Partha Sarathi , Daniel Rhea , Navarro Fernando A.
Published: June 2023

Functional abdominal pain disorders (FAPDs) affect up to 25% of children in the United States. These disorders are more recently known as disorders of “brain-gut” interaction. The diagnosis is based on the ROME IV criteria, and requires the absence of an organic condition to explain the symptoms. Although these disorders are not completely understood, several factors have been involved in the pathophysiology including disordered gut motility, visceral hypersensitivity, allergies, anxiety/stress, gastrointestinal infection/inflammation, as well dysbiosis of the gut microbiome. The pharmacologic and non-pharmacologic treatments for FAPDs are directed to modifying these pathophysiologic mechanisms. This review aims to summarize the non-pharmacologic interventions used in the treatment of FAPDs including dietary modifications, manipulation of the gut microbiome (neutraceuticals, prebiotics, probiotics, synbiotics and fecal microbiota transplant) and psychological interventions that addresses the “brain” component of the brain-gut axis (cognitive behavioral therapy, hypnotherapy, breathing and relaxation techniques). In a survey conducted at a large academic pediatric gastroenterology center, 96% of patients with functional pain disorders reported using at least 1 complementary and alternative medicine treatment to ameliorate symptoms. The paucity of data supporting most of the therapies discussed in this review underscores the need for large randomized controlled trials to assess their efficacy and superiority compared to other treatments.
DeepCTG® 1.0: an interpretable model to detect fetal hypoxia from cardiotocography data during labor and delivery
Authors: Ben M’Barek Imane , Jauvion Grégoire , Vitrou Juliette , Holmström Emilia , Koskas Martin , Ceccaldi Pierre-François
Published: June 2023

Introduction

Cardiotocography, which consists in monitoring the fetal heart rate as well as uterine activity, is widely used in clinical practice to assess fetal wellbeing during labor and delivery in order to detect fetal hypoxia and intervene before permanent damage to the fetus. We present DeepCTG® 1.0, a model able to predict fetal acidosis from the cardiotocography signals.

Materials and methods

DeepCTG® 1.0 is based on a logistic regression model fed with four features extracted from the last available 30 min segment of cardiotocography signals: the minimum and maximum values of the fetal heart rate baseline, and the area covered by accelerations and decelerations. Those four features have been selected among a larger set of 25 features. The model has been trained and evaluated on three datasets: the open CTU-UHB dataset, the SPaM dataset and a dataset built in hospital Beaujon (Clichy, France). Its performance has been compared with other published models and with nine obstetricians who have annotated the CTU-UHB cases. We have also evaluated the impact of two key factors on the performance of the model: the inclusion of cesareans in the datasets and the length of the cardiotocography segment used to compute the features fed to the model.

Results

The AUC of the model is 0.74 on the CTU-UHB and Beaujon datasets, and between 0.77 and 0.87 on the SPaM dataset. It achieves a much lower false positive rate (12% vs. 25%) than the most frequent annotation among the nine obstetricians for the same sensitivity (45%). The performance of the model is slightly lower on the cesarean cases only (AUC = 0.74 vs. 0.76) and feeding the model with shorter CTG segments leads to a significant decrease in its performance (AUC = 0.68 with 10 min segments).

Discussion

Although being relatively simple, DeepCTG® 1.0 reaches a good performance: it compares very favorably to clinical practice and performs slightly better than other published models based on similar approaches. It has the important characteristic of being interpretable, as the four features it is based on are known and understood by practitioners. The model could be improved further by integrating maternofetal clinical factors, using more advanced machine learning or deep learning approaches and having a more robust evaluation of the model based on a larger dataset with more pathological cases and covering more maternity centers.
Reconstructing individual responses to direct questions: a new method for reconstructing malingered responses
Authors: Orrù Graziella , Ordali Erica , Monaro Merylin , Scarpazza Cristina , Conversano Ciro , Pietrini Pietro , Gemignani Angelo , Sartori Giuseppe
Published: June 2023

Introduction

The false consensus effect consists of an overestimation of how common a subject opinion is among other people. This research demonstrates that individual endorsement of questions may be predicted by estimating peers’ responses to the same question. Moreover, we aim to demonstrate how this prediction can be used to reconstruct the individual’s response to a single item as well as the overall response to all of the items, making the technique suitable and effective for malingering detection.

Method

We have validated the procedure of reconstructing individual responses from peers’ estimation in two separate studies, one addressing anxiety-related questions and the other to the Dark Triad. The questionnaires, adapted to our scopes, were submitted to the groups of participants for a total of 187 subjects across both studies. Machine learning models were used to estimate the results.

Results

According to the results, individual responses to a single question requiring a “yes” or “no” response are predicted with 70–80% accuracy. The overall participant-predicted score on all questions (total test score) is predicted with a correlation of 0.7–0.77 with actual results.

Discussion

The application of the false consensus effect format is a promising procedure for reconstructing truthful responses in forensic settings when the respondent is highly likely to alter his true (genuine) response and true responses to the tests are missing.
Student athlete well-being framework: an empirical examination of elite college student athletes
Authors: Sato Shintaro , Kinoshita Keita , Kondo Midori , Yabunaka Yuki , Yamada Yaeko , Tsuchiya Hironobu
Published: June 2023

The current study proposes a multidimensional student athlete well-being framework (SAWBF). The authors used 12 items to capture SAWBF comprised of four well-being dimensions (i.e., physical, hedonic, psychological, and social well-being). To empirically assess the reliability and validity of the framework, data from elite collegiate student athletes in Japan (N = 546) were procured. The results indicated sufficient convergent and discriminant validities of SAWBF. The authors also assessed predictive validity correlations of the framework by focusing on the oft-supported well-being outcome–organizational citizenship behavior, which were also found to be associated with SAWBF. The findings indicated the usefulness of SAWBF; and coaches and staff members can utilize the framework to multi-dimensionally understand well-being status of their student athletes, potentially boosting adaptive behaviors.
Do information publicity and moral norms trigger waste-sorting intention among households? A sequential mediation analysis
Authors: Li Yan , Bhutto Muhammad Yaseen , Sun Chaojing , Mehdi Syed Muntazir
Published: June 2023

Introduction

The quick pace of technological advancement and urbanization has led to a significant increase in waste production, severely damaging environmental quality and human health. The sorting of waste is a viable option to reduce environmental hazards and attain high recovery rates in the cities. This research extended the theory of planned behavior (TPB) by integrating information publicity (IP) and moral norms (MNs).

Methods

A conceptual model has been developed to explore the predictors of waste-sorting intention of households. The data from 361 Pakistani households have been collected using the purposive sampling method and analyzed via PLS-SEM.

Results and discussion

The study's results revealed that IP is important in creating awareness and establishing moral norms regarding waste sorting among households. The findings further confirm that MN, attitude (ATD), subjective norms (SNs), and perceived behavioral control (PBC) sequentially mediate between IP and WSI. The findings of the current study provides useful practical implications to the practitioners and academicians to combat environmental pollution.
Heterotypic and homotypic continuity in psychopathology: a narrative review
Authors: Speranza Anna Maria , Liotti Marianna , Spoletini Ilaria , Fortunato Alexandro
Published: June 2023

Psychopathology is a process: it unfolds over time and involves several different factors. To extend our knowledge of such process, it is vital to understand the trajectories that lead to developing and maintaining a specific disorder. The construct of continuity appears very useful to this aim. It refers to the consistency, similarity, and predictability of behaviors or internal states across different developmental phases. This paper aims to present a narrative review of the literature on homotypic and heterotypic continuity of psychopathology across the lifespan. A detailed search of the published literature was conducted using the PsycINFO Record and Medline (PubMed) databases. Articles were included in the review based on the following criteria: (1) publication dates ranging from January 1970 to October 2022; and (2) articles being written in the English language. To ensure a thorough investigation, multiple combinations of keywords such as “continuity,” “psychopathology,” “infancy,” “childhood,” “adolescence,” “adulthood,” “homotypic,” and “heterotypic” were used. Articles were excluded if exclusively focused on epidemiologic data and if not specifically addressing the topic of psychopathology continuity. The literature yielded a total of 36 longitudinal studies and an additional 190 articles, spanning the research published between 1970 and 2022. Studies on continuity focus on the etiology of different forms of mental disorders and may represent a fundamental resource from both a theoretical and clinical perspective. Enhancing our understanding of the different trajectories beneath psychopathology may allow clinicians to implement more effective strategies, focusing both on prevention and intervention. Since literature highlights the importance of early detection of clinical signs of psychopathology, future research should focus more on infancy and pre-scholar age.
Associations between the use of psychedelics and other recreational drugs with mental health and resilience during the COVID-19 pandemic
Authors: Bălăeț Maria , Trender William , Hellyer Peter J. , Hampshire Adam
Published: June 2023

The large-scale disruption to peoples’ daily lives during the COVID-19 pandemic provides a context for examining whether use of substances such as psychedelics in a naturalistic (outside of a controlled environment) setting, is associated with better mental wellbeing and resilience relative to those who use other drugs, or who do not use drugs at all. We interrogate data from the Great British Intelligence Test and identify that 7.8% out of N = 30,598 unique respondents used recreational drugs inclusive of psychedelics, cannabis, cocaine, and MDMA during the COVID-19 pandemic. Recruitment materials did not mention drug use would be surveyed, thereby enabling us to model the relationship with mood and resilience in people who had not specifically self-selected themselves for a ‘drug’ study. We report that people form clusters, characterized by different real-world patterns of drug use, and the majority of psychedelics users also use cannabis. However, a subset of cannabis users do not use psychedelics, enabling a subtractive comparison. Those who primarily used psychedelics and cannabis during the COVID-19 pandemic had worse mood self-assessment and resilience scores compared to those who never used drugs or primarily used cannabis. This pattern was also evident for other recreational drug use clusters, except for those who primarily used MDMA and cannabis, who had better mood but were of too low incidence to have confidence in this estimate. These findings cast light on the significant differences in mental wellbeing between users of different drugs and the non-user population during a global-crisis and call for future research to explore the pharmacological, contextual and cultural variables associated with these differences, their generalisability and causal links with greater precision.
Gender specific sexual dysfunction in patients with depression
Authors: Liu Xinyu , Feng Zizhao , Galling Britta , Qi Na , Zhu Xue-quan , Xiao Le , Wang Gang
Published: June 2023

Background

This study aims to investigate the factors associated with sexual dysfunction (SD), with a particular focus on the influence of sex on the occurrence and severity of this condition in patients with major depressive disorder (MDD).

Method

Sociodemographic and clinical assessments were conducted on 273 patients with MDD (female = 174, male = 99), including the ASEX, QIDS-SR16, GAD-7, and PHQ-15. Univariate analyses, independent samples t-test, Chi-square test, and Fisher’s exact test were used as appropriate, and logistic regression analysis was used to identify correlation factors for SD. Statistical analyses were performed using the Statistical Analysis System (SAS 9.4).

Result

SD was reported in 61.9% of the participants (ASEX score = 19.6 ± 5.5), and the prevalence of it in females (75.3%, ASEX score = 21.1 ± 5.4) was significantly higher than that in males (38.4%, ASEX score = 17.1 ± 4.6). Factors associated with SD included being female, being aged 45 years or above, having a low monthly income (≤750 USD), feeling more sluggish than usual (a QIDS-SR16 Item 15 score of 1 or above), and having somatic symptoms (evaluated with the total score of PHQ15).

Limitation

The use of antidepressants and antipsychotics might be a confounding factor affecting sexual function. Also, the lack of information in the clinical data regarding the number, duration, and time of onset of the episodes limits the richness of the results.

Conclusion

Our findings reveal the sex differences in the prevalence and severity of SD in patients with MDD. Evaluated with the ASEX score, female patients showed significantly worse sexual function than male patients. Being female, having a low monthly income, being aged 45 years or above, feeling sluggish, and having somatic symptoms may increase the risk of SD in patients with MDD.