bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of Cutis Laxa
Authors: Beyens Aude , Callewaert Bert 
Published: July 2023

Abstract

Cutis laxa syndromes are a heterogeneous group of multisystem disorders with prominent connective tissue features including loose redundant skin folds, a clinical hallmark shared among all subtypes. The skin laxity results from severe dermal elastic fibre fragmentation. The molecular defects underlying congenital forms of cutis laxa may affect any step in elastic fibre assembly, as illustrated by the identification of pathogenic variants in different extracellular matrix proteins, including elastin, latent transforming growth factor β proteins and fibulins (
ELN
,
LTBP4
,
FBLN4
,
FBLN5, LOX, EMILIN1, LTPB1
), cellular trafficking (
ATP6V0A2, ATP6V1E1, ATP6V1A
and
ATP7A
) and metabolic processes (
ALDH18A1, PYCR1)
. The latter two groups have been referred to as neurometabolic cutis laxa and may present with skeletal and neurological phenotypes in addition to connective tissue manifestations.

Key Concepts

Elastic fibres (EF) provide resilience and elasticity to the connective tissue and contribute to tissue homeostasis by regulating cytokine signalling and cell–matrix interactions.

Elastic fibre synthesis or elastogenesis is a complex spatiotemporally regulated multistep process.

Cutis laxa syndromes are a heterogeneous group of multisystem connective tissue disorders that share loose redundant skin folds, that vary significantly in severity and spectrum of the associated clinical manifestations.

The molecular defects underlying congenital forms of cutis laxa involve all steps in EF synthesis, affecting different extracellular matrix proteins (
ELN, LTBP4, FBLN4, FBLN5, LOX, EMILIN1, LTBP1
), cellular trafficking (
ATP6V0A2, ATP6V1E1, ATP6V1A, SCYL1BP1 and ATP7A
) and metabolism (
ALDH18A1, PYCR1
).

Cutis laxa caused by defects in extracellular matrix proteins present with prominent arterial and/or pulmonary abnormalities.

Cutis laxa caused by intracellular trafficking disorders and/or metabolic disorders may present with intellectual deficiency, skeletal and/or ocular defects.
Genetics of Motor Neuron Diseases
Authors: Chaudhary Rishabh , Mishra Vikas 
Published: July 2023

Abstract

Motor neuron diseases, also known as MNDs, are a group of extremely severe neurological conditions that, in most cases, result in death. These diseases are primarily characterised by the gradual degeneration and/or loss of motor neurons in the brainstem and spinal cord regions. Genetic mutations are one of the main triggers of MND pathogenesis, and researchers have identified more than 100 different genes in humans that have been altered. Previous studies have shown that many of the enzymatic transcriptional products produced by the defective or mutated genes that cause MNDs are involved in the dysregulation of several key intracellular and molecular pathways that are essential for proper motor neuron functioning. These include RNA transport and splicing, protein homeostasis, microglial cell activation, mitochondrial functions, axonal protein transport, protein folding and many more.

Key Concepts

Motor neuron disease is a fatal neurodegenerative condition that affects motor neurons in the central nervous system.

Genetic factors play a major role in the initiation and progression of motor neuron disease.

Over the past few years, hundreds of genes that play causative roles in motor neuron disorders have been discovered.

Identifying novel genes or rare genetic variants involved in motor neuron disease pathophysiology is extremely vital.

The use of various high‐throughput gene sequencing techniques has been shown to be an effective tool for discovering genes related to motor neuron diseases.

Alterations in the expression of genes in motor neuron disease cause dysregulation of several intracellular pathways that are essential for healthy motoneuron functioning.

The mechanism underlying the death of motor neurons is influenced by a number of different cellular and molecular processes.

Toxic gain‐of‐function or loss‐of‐function of a specific protein causes abnormalities in synapse mechanisms, which leads to the degeneration or death of motor neurons.

Even though the first case of motor neuron disease was documented more than a century ago, there is still no effective treatment or a viable cure available for the disease.

At present, managing disease symptoms and providing palliative care are still the main goals of motor neuron disease therapy.
Interpretation of Variants in Clinical Genomics
Authors: Jackson Maria , Stobo Daniel 
Published: July 2023

Abstract

Many health conditions are genetic in origin, and it is often necessary to identify the causative DNA variant(s) in the patient in order to confirm a potential genetic diagnosis, so that optimal management and/or treatment can be implemented. This process can be complicated by the massive amount of variation present in all our genomes, so that distinguishing pathogenic variants from benign ones can be challenging. In order to provide consistency and improved validity of interpretations from different diagnostic laboratories across the world, professional guidelines have recently been published which specify how various types of evidence from scientific literature, databases, functional studies and
in silico
analysis should be combined to generate a classification for a variant. Ongoing work seeks to improve these guidelines, including the generation of versions specific for particular conditions and specific guidelines for classification of copy number variants and somatic variants.

Key Concepts

Analysis of patient DNA to identify pathogenic variants is often a critical step in confirming a genetic diagnosis.

Most of the variants found in any human genome are benign, so clinical scientists need to be able to identify which are (likely) pathogenic.

Other reports of a variant, in scientific literature or databases, and/or reports from functional assays can help to classify variants as (likely) benign or (likely) pathogenic.

Computer software can be used to conduct
in silico
analysis to predict potential pathogenicity of a variant.

Professional guidelines have been generated for combining different types of evidence during variant interpretation, and these are used internationally, to ensure consistent outcomes in variant interpretation, both in general use and for specific genetic conditions.

Despite careful evaluation according to the guidelines, many variants identified in patient DNA remain as variants of uncertain significance (VUS) due to insufficient or contradictory evidence.
Self‐Fertilising Populations and Adaptation
Authors: Clo Josselin 
Published: July 2023

Abstract

The evolution to self‐fertilisation from outcrossing is one of the most frequent transitions in mating strategies. Recurrent self‐fertilisation, and inbreeding in general, is thought to lead to a reduction in adaptive capacities, thus leading selfing lineages down an evolutionary ‘blind alley’. A centenary of empirical and theoretical research studied in which conditions the evolution of self‐fertilisation is associated with a reduction in adaptive potential, notably when adaptation occurs thanks to
de novo
mutations and standing genetic diversity. Recent results suggest that adaptation from de novo mutations is less likely in selfing populations compared to outcrossing ones, while adaptation from standing genetic diversity is at least as likely.

Key Concepts

Adaptation from
de novo
mutations is limited in self‐fertilising populations because of selective interference at other loci.

The quantitative genetics of inbred populations is complex because of the joint inheritance of additive and dominance variances.

Recent models and meta‐analyses have shown that self‐fertilisation does not lead to a reduction of the heritable genetic diversity.

Self‐fertilization is ubiquitous in plants and animals kingdoms, with 70% of angiosperm species self‐fertilizing to some extent.

Self‐fertilization is often described as an evolutionary dead‐end, notably due to limited capacities to adapt to new environmental conditions.
Companion Cell and Sieve Elements
Authors: Kim Ji‐Yun , Frommer Wolf B 
Published: July 2023

Abstract

Companion cells and sieve elements are two cell types that are key components of the phloem – a tissue responsible for the translocation of inorganic and organic compounds as well as signals from the leaves to the sites of use. Companion cells form a functional unit with the sieve elements for long‐distance translocation of assimilates, nutrients and signalling molecules and play indispensable roles throughout the life cycle of plants.

Key Concepts

Sieve elements are cells specialised in translocation of phloem sap.

Sieve elements degrade their nucleus and other organelles during development to produce a conduit

Enucleate sieve elements are kept alive by the tightly connected companion cells.

Plasmodesmata connect companion cells and sieve elements, likely to provide conduits for the exchange of ions, metabolites, hormones, RNAs and proteins.

The sieve element companion cell complex is specialised in phloem loading, in the case of sucrose via SUT sucrose/H
+
symporters, in the case of amino acids via AAP amino acid/H
+
symporters.

Other specialised forms of companion cells include transfer cells and intermediary cells, characterised either by increased plasma membrane surface due to reticulate cell wall invaginations or specialised metabolism for raffinose translocation.

Companion cells play crucial roles in hosting diverse metabolic and signalling processes.
Phenotypic and Developmental Plasticity in Plants
Authors: Bush Susan M 
Published: July 2023

Abstract

Plants have a remarkable ability to alter their development in response to a multitude of environmental cues or stressors. This phenotypic plasticity allows them to continually adapt to their local environment, a necessity for plants as immobile, sessile organisms. A host of environmental cues can be interpreted by plants, including light, temperature, water, and nutrient levels, and these inputs are integrated and translated into a range of developmental outputs from shoot elongation, regulation of root gravitropism, altered flowering time, timing of germination, and overall plant yield. Plasticity enables growth optimisation for a plant's local environment, allows expansion of a species' range into heterogeneous habitats, and may provide an advantage as the changing climate affects growth conditions around the globe. Studies in the model organism
Arabidopsis thaliana
, as well as in economically important crop plants like tomato and wheat, are helping to more thoroughly define molecular mechanisms for plastic growth responses. Moving forward, studies of growth and plasticity of plants under multiple, integrated stress conditions will help expand our knowledge and abilities to grow crops in a changing climate and feed our ever‐expanding population.

Key Concepts

Phenotypic plasticity is the ability of a single genotype to produce a range of phenotypes in response to different environmental conditions.

The type and degree of a plant's developmental plasticity will help determine future success of individuals and species in changing climates or altered habitats.

Multiple environmental signals are integrated to regulate plant growth, development, and yield.

Developmental plasticity comes from the meristem, which continuously produces organs throughout the plant's life cycle.

Environmental cues can lead to changes in a plant's gene expression and protein abundance, phytohormone‐responsive signalling, and also epigenetic modifications to the plant's genome.

Natural genetic variation within a plant species can confer variable plasticity of development in response to a single abiotic stressor, causing some varieties of plants to be hardier than others.
Floral Meristems
Authors: Schneitz Kay , Mukherjee Sourav , Balasubramanian Sureshkumar 
Published: July 2023

Abstract

Meristems refer to a group of undifferentiated dividing cells that are responsible for the formation of plant organs. Floral meristems are a group of dividing cells that give rise to flowers. The formation of a floral meristem and its subsequent fate are under both environmental and molecular control. Several exogenous environmental factors and a complex network of genes control this process.

Key Concepts

Meristems refer to a group of undifferentiated dividing cells that form diverse plant organs.

Shoot and root apical meristems give raise to above‐ground and below‐ground plant organs.

Shoot apical meristem produces leaves at its flanks in the vegetative state and flowers in the reproductive state.

Floral meristems are a group of dividing cells that give rise to flowers.

The formation of a floral meristem and its subsequent fate are under both environmental and molecular control.

Several exogenous environmental factors and a complex network of genes control this process.
Medicinal Cannabis Use for Rheumatic Conditions in the US Versus Canada: Rationale for Use and Patient–Health Care Provider Interactions
Authors: Boehnke Kevin F. , Martel Marc O. , Smith Tristin , He Ying , Bergmans Rachel S. , Kruger Daniel J. , Andwele Michele , Bevan Sian , Williams David A. , Fitzcharles Mary‐Ann 
Published: July 2023

ObjectiveUnderstanding how medical cannabis (MC) use is integrated into medical practice for rheumatic disease management is essential. We characterized rationale for MC use, patient–physician interactions around MC, and MC use patterns among people with rheumatic conditions in the US and Canada.MethodsWe surveyed 3406 participants with rheumatic conditions in the US and Canada, with 1727 completing the survey (50.7% response rate). We assessed disclosure of MC use to health care providers, MC authorization by health care providers, and MC use patterns and investigated factors associated with MC disclosure to health care providers in the US versus Canada.ResultsOverall, 54.9% of US respondents and 78.0% of Canadians reported past or current MC use, typically because of inadequate symptom relief from other medications. Compared to those in Canada, fewer US participants obtained MC licenses, disclosed MC use to their health care providers, or asked advice on how to use MC (all P values <0.001). Overall, 47.4% of Canadian versus 28.2% of US participants rated their medical professionals as their most trusted information source. MC legality in state of residence was associated with 2.49 greater odds of disclosing MC use to health care providers (95% confidence interval: 1.49‐4.16, P < 0.001) in the US, whereas there were no factors associated with MC disclosure in Canada. Our study is limited by our convenience sampling strategy and cross‐sectional design.ConclusionDespite widespread availability, MC is poorly integrated into rheumatic disease care, with most patients self‐directing use with minimal or no clinical oversight. Concerted efforts to integrate MC into education and clinical policy is critical.
Adaptive state observation of linear time‐varying systems with switching unknown parameters: Application to gain scheduling and event‐triggered control
Authors: Romero Jose Guadalupe , Ortega Romeo 
Published: July 2023

SummaryMotivated by its application in gain scheduling and event‐triggered controllers we propose in this paper an adaptive observer for linear time‐varying (LTV) systems with unknown switching parameters, but known switching time instants. To construct the observer we propose an extension to the generalized parameter estimation‐based observers (GPEBO), which we combine with the least‐squares plus dynamic regression extension and mixing (LS+DREM) estimator recently proposed. We prove that the system state and the parameters converge infinite timeinside each switching sub‐interval, under the weak assumption of interval‐excitation (IE). The excellent performance of the proposed observer is illustrated with a practical and an academic example both reported in the literature.
Biohybrid Hydrogels for Tumoroid Culture
Authors: Castellote‐Borrell Miquel , Merlina Francesca , Rodríguez Adrián R. , Guasch Judith 
Published: July 2023

AbstractTumoroids are 3D in vitro models that recapitulate key features of in vivo tumors, such as their architecture — hypoxic center and oxygenated outer layer — in contrast with traditional 2D cell cultures. Moreover, they may be able to preserve the patient‐specific signature in terms of cell heterogeneity and mutations. Tumoroids are, therefore, interesting tools for improving the understanding of cancer biology, developing new drugs, and potentially designing personalized therapeutic plans. Currently, tumoroids are most often established using basement membrane extracts (BME), which provide a multitude of biological cues. However, BME are characterized by a lack of well‐defined composition, limited reproducibility, and potential immunogenicity as a consequence of their natural origin. Synthetic polymers can overcome these problems but lack structural and biochemical complexity, which can limit the functional capabilities of organoids. Biohybrid hydrogels consisting of both natural and synthetic components can combine their advantages and offer superior 3D culture systems. In this review, it is summarized efforts devoted to producing tumoroids using different types of biohybrid hydrogels, which are classified according to their crosslinking mechanism.
Construction and Validation of a Prognostic Model Based on Novel Senescence‐Related Genes in Non‐Small Cell Lung Cancer Patients with Drug Sensitivity and Tumor Microenvironment
Authors: Liu Xiwen , Lin Lixuan , Cai Qi , Sheng Hongxu , Zeng Ruiqi , Zhao Yi , Qiu Xinyi , Liu Huiting , Huang Linchong , Liang Wenhua , He Jianxing 
Published: July 2023

AbstractCellular senescence contributes to cancer pathogenesis and immune regulation. Using the LASSO Cox regression, we developed a 12‐gene prognostic signature for lung adenocarcinoma (LUAD) from The Cancer Genome Atlas (TCGA) and a Gene Expression Omnibus (GEO) dataset. We assessed gene expression, drug sensitivity, immune infiltration, and conducted cell line experiments. High‐risk LUAD patients showed increased mortality risk and shorter survival (P < 0.001). Senescence‐related gene analysis indicated differences in protein phosphorylation and DNA methylation between normal individuals and LUAD patients. The high‐risk group showed a positive association with PD‐L1 expression (P = 0.003). Single‐cell sequencing data suggested PEBP1 might significantly impact T cell infiltration. We predicted potential sensitive compounds for 12 senescence genes and found GAPDH promoted cell line proliferation. We established a novel prognostic system based on a newly identified senescence gene. High‐risk patients had elevated immunosuppressive markers, and PEBP1 might influence T cell infiltration significantly. GAPDH, expressed at higher levels in tumors, could affect cancer progression. Our drug prediction model may guide treatment selection.
Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery
Authors: Attia Lucas , Chen Liang‐Hsun , Doyle Patrick S. 
Published: July 2023

AbstractHydrophobic active pharmaceutical ingredients (APIs) are ubiquitous in the drug development pipeline, but their poor bioavailability often prevents their translation into drug products. Industrial processes to formulate hydrophobic APIs are expensive, difficult to optimize, and not flexible enough to incorporate customizable drug release profiles into drug products. Here, a novel, dual‐responsive gelation process that exploits orthogonal thermo‐responsive and ion‐responsive gelations is introduced. This one‐step “dual gelation” synthesizes core–shell (methylcellulose‐alginate) hydrogel particles and encapsulates drug‐laden nanoemulsions in the hydrogel matrices. In situ crystallization templates drug nanocrystals inside the polymeric core, while a kinetically stable amorphous solid dispersion is templated in the shell. Drug release is explored as a function of particle geometry, and programmable release is demonstrated for various therapeutic applications including delayed pulsatile release and sequential release of a model fixed‐dose combination drug product of ibuprofen and fenofibrate. Independent control over drug loading between the shell and the core is demonstrated. This formulation approach is shown to be a flexible process to develop drug products with biocompatible materials, facile synthesis, and precise drug release performance. This work suggests and applies a novel method to leverage orthogonal gel chemistries to generate functional core–shell hydrogel particles.
Emerging Advances of Liquid Metal toward Flexible Sensors
Authors: Qin Jinghan , Cui Dandan , Ren Long , Hao Weichang , Shi Yan , Du Yi 
Published: July 2023

AbstractWith the rising demand for biosignal detection, many wearable sensors emerge in recent years. Such a new generation of sensors relies on major breakthroughs in soft sensing materials, which can be bent, compressed, and stretched in a large range. Ga‐based liquid metals (LM) offer a unique combination of high deformability, electrical conductivity, and biocompatibility, making them ideal functional candidate materials for wearable sensors. Numerous studies design various LM sensors for detecting and modulating diverse signals. Nevertheless, further systematic discussion is still missing regarding their operational mechanism, structure defects, and potential solutions. In this review, recent progress in the application of Ga‐based LM sensors is summarized and discussed, with a focus on the sensing principles corresponding to distinct LM properties, the problems, and solutions to each type of sensor. The key challenges toward biosignal detection and future research orientations are discussed.
Tuning Phase Purity in Chiral 2D Perovskites
Authors: Scalon Lucas , Brunner Julius , Guaita Maria Gabriella Detone , Szostak Rodrigo , Albaladejo‐Siguan Miguel , Kodalle Tim , Guerrero‐León L. Andrés , Sutter‐Fella Carolin M. , Oliveira Caio C. , Vaynzof Yana , Nogueira Ana Flavia 
Published: July 2023

AbstractThe introduction of chiral organic spacers in low‐dimensional metal‐halide perovskites triggers chiroptical activity, which is appealing for spintronic applications. However, a comprehensive understanding of structure formation and the ability to control phase purity in such materials have yet to be developed. Herein, the impact of processing conditions on the phase purity, microstructure, and chiroptical properties of chiral 2D perovskites is explored. The anisotropic emergence of a 1D perovskite inside the 2D matrix and its dependence on the organic cation chirality, solvent, and thermal annealing conditions are shown. By controlling these parameters, the in‐plane conductivity of the films is nearly doubled. Furthermore, it is demonstrated, for the first time, that solvent choice and the spatial configuration of the organic cation can have an impact on the residual lattice strain and the energetic disorder of the system. The fundamentals presented here can help to improve the film deposition methods for low‐dimensional chiral perovskites, offering strategies to control phase purity.