bluuebunny/crossref_metadata_2025_split huggingface dataset:
The predictive value of cortisol in psychodynamic psychotherapy for social anxiety disorder: Extended results of the SOPHONET-Study
Authors: Schmalbach Ileana , Witthöft Michael , Strauß Bernhard , Joraschky Peter , Petrowski Katja 
Published: April 2024

AbstractPsychotherapy is an effective treatment for anxiety disorders (AD), yet a vast majority of patients do not respond to therapy, necessitating the identification of predictors to enhance outcomes. Several studies have explored the relationship between stress response and treatment outcome, as a potential treatment mechanism. However, the latter remains under-researched in patients with social anxiety disorder (SAD). We studied N = 29 patients undergoing psychodynamic psychotherapy (PDT) within the SOPHONET-Study. Stress reactivity (i.e., area under the curve with respect to the increase; AUCi) was induced by a standardized psychosocial stressor (Trier Social Stress Test; TSST) and assessed by means of adrenocorticotropic hormone (ACTH), blood and salivary cortisol samples before (t1) treatment. Samples of these biomarkers were taken −1 min prior stress exposure and six more blood samples were collected post-TSST ( + 1, + 10, + 20, + 30, + 45, + 60 min.). The participants were diagnosed with SAD based on the Structured Clinical Interview for DSM-IV (SCID) and completed the Liebowitz Social Anxiety Scale as well as the Beck Depression Inventory before (t1) and after psychotherapy (t2). Pre-treatment stress reactivity significantly predicted changes in depression (salivary p < 0.001 and blood cortisol p = 0.001), as well as in avoidance behavior (blood cortisol p = 0.001). None of the biomarkers revealed significant results in fear or in the total LSAS-scores, except for ACTH with a trend finding (p = 0.06). Regarding therapy success, symptoms of social anxiety (p = 0.005) and depression (p < 0.001) were significantly reduced from pre (t1) to post-treatment (t2). Our study showed that stress reactivity pre-treatment may serve as a predictor of psychotherapy outcome. In this regard, alterations in stress response relate to changes in symptoms of social anxiety and depression after PDT. This implies that patients with chronic stress might benefit from a targeted interventions during psychotherapy, especially to manage fear in social contexts.
An updated review on animal models to study attention-deficit hyperactivity disorder
Authors: Kim Daegeon , Yadav Dhananjay , Song Minseok 
Published: April 2024

AbstractAttention-deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder affecting both children and adolescents. Individuals with ADHD experience heterogeneous problems, such as difficulty in attention, behavioral hyperactivity, and impulsivity. Recent studies have shown that complex genetic factors play a role in attention-deficit hyperactivity disorders. Animal models with clear hereditary traits are crucial for studying the molecular, biological, and brain circuit mechanisms underlying ADHD. Owing to their well-managed genetic origins and the relative simplicity with which the function of neuronal circuits is clearly established, models of mice can help learn the mechanisms involved in ADHD. Therefore, in this review, we highlighting the important genetic animal models that can be used to study ADHD.
OTUD5 promotes the inflammatory immune response by enhancing MyD88 oligomerization and Myddosome formation
Authors: Liu Yaxing , Yuan Jiahua , Zhang Yuling , Qin Fei , Bai Xuemei , Sun Wanwei , Chen Tian , Liu Feng , Zheng Yi , Qi Xiaopeng , Zhao Wei , Liu Bingyu , Gao Chengjiang 
Published: April 2024

AbstractMyddosome is an oligomeric complex required for the transmission of inflammatory signals from TLR/IL1Rs and consists of MyD88 and IRAK family kinases. However, the molecular basis for the self-assemble of Myddosome proteins and regulation of intracellular signaling remains poorly understood. Here, we identify OTUD5 acts as an essential regulator for MyD88 oligomerization and Myddosome formation. OTUD5 directly interacts with MyD88 and cleaves its K11-linked polyubiquitin chains at Lys95, Lys231 and Lys250. This polyubiquitin cleavage enhances MyD88 oligomerization after LPS stimulation, which subsequently promotes the recruitment of downstream IRAK4 and IRAK2 to form Myddosome and the activation of NF-κB and MAPK signaling and production of inflammatory cytokines. Consistently, Otud5-deficient mice are less susceptible to LPS- and CLP-induced sepsis. Taken together, our findings reveal a positive regulatory role of OTUD5 in MyD88 oligomerization and Myddosome formation, which provides new sights into the treatment of inflammatory diseases.
FOXA1 and FOXA2: the regulatory mechanisms and therapeutic implications in cancer
Authors: Liu Na , Wang Anran , Xue Mengen , Zhu Xiaoren , Liu Yang , Chen Minbin 
Published: April 2024

AbstractFOXA1 (Forkhead Box A1) and FOXA2 (Forkhead Box A2) serve as pioneering transcription factors that build gene expression capacity and play a central role in biological processes, including organogenesis and differentiation, glycolipid metabolism, proliferation, migration and invasion, and drug resistance. Notably, FOXA1 and FOXA2 may exert antagonistic, synergistic, or complementary effects in the aforementioned biological processes. This article focuses on the molecular mechanisms and clinical relevance of FOXA1 and FOXA2 in steroid hormone-induced malignancies and highlights potential strategies for targeting FOXA1 and FOXA2 for cancer therapy. Furthermore, the article describes the prospect of targeting upstream regulators of FOXA1/FOXA2 to regulate its expression for cancer therapy because of the drug untargetability of FOXA1/FOXA2.
Chromosome 20p11.2 deletions cause congenital hyperinsulinism via the loss of FOXA2 or its regulatory elements
Authors: Laver Thomas W. , Wakeling Matthew N. , Caswell Richard C. , Bunce Benjamin , Yau Daphne , Männistö Jonna M. E. , Houghton Jayne A. L. , Hopkins Jasmin J. , Weedon Michael N. , Saraff Vrinda , Kershaw Melanie , Honey Engela M. , Murphy Nuala , Giri Dinesh , Nath Stuart , Tangari Saredo Ana , Banerjee Indraneel , Hussain Khalid , Owens Nick D. L. , Flanagan Sarah E. 
Published: April 2024

AbstractPersistent congenital hyperinsulinism (HI) is a rare genetically heterogeneous condition characterised by dysregulated insulin secretion leading to life-threatening hypoglycaemia. For up to 50% of affected individuals screening of the known HI genes does not identify a disease-causing variant. Large deletions have previously been used to identify novel regulatory regions causing HI. Here, we used genome sequencing to search for novel large (>1 Mb) deletions in 180 probands with HI of unknown cause and replicated our findings in a large cohort of 883 genetically unsolved individuals with HI using off-target copy number variant calling from targeted gene panels. We identified overlapping heterozygous deletions in five individuals (range 3–8 Mb) spanning chromosome 20p11.2. The pancreatic beta-cell transcription factor gene, FOXA2, a known cause of HI was deleted in two of the five individuals. In the remaining three, we found a minimal deleted region of 2.4 Mb adjacent to FOXA2 that encompasses multiple non-coding regulatory elements that are in conformational contact with FOXA2. Our data suggests that the deletions in these three children may cause disease through the dysregulation of FOXA2 expression. These findings provide new insights into the regulation of FOXA2 in the beta-cell and confirm an aetiological role for chromosome 20p11.2 deletions in syndromic HI.
Further evidence supporting the role of GTDC1 in glycine metabolism and neurodevelopmental disorders
Authors: Errichiello Edoardo , Lecca Mauro , Vantaggiato Chiara , Motta Zoraide , Zanotta Nicoletta , Zucca Claudio , Bertuzzo Sara , Piubelli Luciano , Pollegioni Loredano , Bonaglia Maria Clara 
Published: April 2024

AbstractCopy number variants (CNVs) represent the genetic cause of about 15–20% of neurodevelopmental disorders (NDDs). We identified a ~67 kb de novo intragenic deletion on chromosome 2q22.3 in a female individual showing a developmental encephalopathy characterised by epilepsy, severe intellectual disability, speech delay, microcephaly, and thin corpus callosum with facial dysmorphisms. The microdeletion involved exons 5-6 of GTDC1, encoding a putative glycosyltransferase, whose expression is particularly enriched in the nervous system. In a previous study, a balanced de novo translocation encompassing GTDC1 was reported in a male child with global developmental delay and delayed speech and language development. Based on these premises, we explored the transcriptomic profile of our proband to evaluate the functional consequences of the novel GTDC1 de novo intragenic deletion in relation to the observed neurodevelopmental phenotype. RNA-seq on the proband’s lymphoblastoid cell line (LCL) showed expression changes of glycine/serine and cytokine/chemokine signalling pathways, which are related to neurodevelopment and epileptogenesis. Subsequent analysis by ELISA (enzyme-linked immunosorbent assay) and HPLC (high-performance liquid chromatography) revealed increased levels of glycine in the proband’s LCL and serum compared to matched controls. Given that an increased level of glycine has been observed in the plasma samples of individuals with Rett syndrome, a condition sharing epilepsy, microcephaly, and intellectual disability with our proband, we proposed that the GTDC1 downregulation is implicated in neurodevelopmental impairment by altering glycine metabolism. Furthermore, our findings expanded the phenotypic spectrum of the novel GTDC1-related condition, including microcephaly and epilepsy among relevant clinical features.
Elevated ozone disrupts mating boundaries in drosophilid flies
Authors: Jiang Nan-Ji , Dong Xinqi , Veit Daniel , Hansson Bill S. , Knaden Markus 
Published: April 2024

AbstractAnimals employ different strategies to establish mating boundaries between closely related species, with sex pheromones often playing a crucial role in identifying conspecific mates. Many of these pheromones have carbon-carbon double bonds, making them vulnerable to oxidation by certain atmospheric oxidant pollutants, including ozone. Here, we investigate whether increased ozone compromises species boundaries in drosophilid flies. We show that short-term exposure to increased levels of ozone degrades pheromones of Drosophila melanogaster, D. simulans, D. mauritiana, as well as D. sechellia, and induces hybridization between some of these species. As many of the resulting hybrids are sterile, this could result in local population declines. However, hybridization between D. simulans and D. mauritiana as well as D. simulans and D. sechellia results in fertile hybrids, of which some female hybrids are even more attractive to the males of the parental species. Our experimental findings indicate that ozone pollution could potentially induce breakdown of species boundaries in insects.
Maximizing carbon sequestration potential in Chinese forests through optimal management
Authors: Yu Zhen , Liu Shirong , Li Haikui , Liang Jingjing , Liu Weiguo , Piao Shilong , Tian Hanqin , Zhou Guoyi , Lu Chaoqun , You Weibin , Sun Pengsen , Dong Yanli , Sitch Stephen , Agathokleous Evgenios 
Published: April 2024

AbstractForest carbon sequestration capacity in China remains uncertain due to underrepresented tree demographic dynamics and overlooked of harvest impacts. In this study, we employ a process-based biogeochemical model to make projections by using national forest inventories, covering approximately 415,000 permanent plots, revealing an expansion in biomass carbon stock by 13.6 ± 1.5 Pg C from 2020 to 2100, with additional sink through augmentation of wood product pool (0.6-2.0 Pg C) and spatiotemporal optimization of forest management (2.3 ± 0.03 Pg C). We find that statistical model might cause large bias in long-term projection due to underrepresentation or neglect of wood harvest and forest demographic changes. Remarkably, disregarding the repercussions of harvesting on forest age can result in a premature shift in the timing of the carbon sink peak by 1–3 decades. Our findings emphasize the pressing necessity for the swift implementation of optimal forest management strategies for carbon sequestration enhancement.
Powder-size driven facile microstructure control in powder-fusion metal additive manufacturing processes
Authors: Chandra Shubham , Wang Chengcheng , Tor Shu Beng , Ramamurty Upadrasta , Tan Xipeng 
Published: April 2024

AbstractMicrostructure control in metal additive manufacturing is highly desirable for superior and bespoke mechanical performance. Engineering the columnar-to-equiaxed transition during rapid solidification in the additive manufacturing process is crucial for its technological advancement. Here, we report a powder-size driven melt pool engineering approach, demonstrating facile and large-scale control in the grain morphology by triggering a counterintuitive response of powder size to the additively manufactured 316 L stainless steel microstructure. We obtain coarse-grained (>100 μm) or near-monocrystalline microstructure using fine powders and near-equiaxed, fine-grained (<10 μm) microstructure using coarse powders. This approach shows resourceful adaptability to directed energy deposition and powder-bed fusion with no added cost, where the particle-size dependent powder-flow preheating effects and powder-bed thermophysical properties drive the microstructural variations. This work presents a pathway for leveraging feedstock particle size distribution towards more controllable, cost-effective, and sustainable metal additive manufacturing.
An adaptive biomolecular condensation response is conserved across environmentally divergent species
Authors: Keyport Kik Samantha , Christopher Dana , Glauninger Hendrik , Hickernell Caitlin Wong , Bard Jared A. M. , Lin Kyle M. , Squires Allison H. , Ford Michael , Sosnick Tobin R. , Drummond D. Allan 
Published: April 2024

AbstractCells must sense and respond to sudden maladaptive environmental changes—stresses—to survive and thrive. Across eukaryotes, stresses such as heat shock trigger conserved responses: growth arrest, a specific transcriptional response, and biomolecular condensation of protein and mRNA into structures known as stress granules under severe stress. The composition, formation mechanism, adaptive significance, and even evolutionary conservation of these condensed structures remain enigmatic. Here we provide a remarkable view into stress-triggered condensation, its evolutionary conservation and tuning, and its integration into other well-studied aspects of the stress response. Using three morphologically near-identical budding yeast species adapted to different thermal environments and diverged by up to 100 million years, we show that proteome-scale biomolecular condensation is tuned to species-specific thermal niches, closely tracking corresponding growth and transcriptional responses. In each species, poly(A)-binding protein—a core marker of stress granules—condenses in isolation at species-specific temperatures, with conserved molecular features and conformational changes modulating condensation. From the ecological to the molecular scale, our results reveal previously unappreciated levels of evolutionary selection in the eukaryotic stress response, while establishing a rich, tractable system for further inquiry.
Dynamics of collective cooperation under personalised strategy updates
Authors: Meng Yao , Cornelius Sean P. , Liu Yang-Yu , Li Aming 
Published: April 2024

AbstractCollective cooperation is essential for many social and biological systems, yet understanding how it evolves remains a challenge. Previous investigations report that the ubiquitous heterogeneous individual connections hinder cooperation by assuming individuals update strategies at identical rates. Here we develop a general framework by allowing individuals to update strategies at personalised rates, and provide the precise mathematical condition under which universal cooperation is favoured. Combining analytical and numerical calculations on synthetic and empirical networks, we find that when individuals’ update rates vary inversely with their number of connections, heterogeneous connections actually outperform homogeneous ones in promoting cooperation. This surprising property undercuts the conventional wisdom that heterogeneous structure is generally antagonistic to cooperation and, further helps develop an efficient algorithm OptUpRat to optimise collective cooperation by designing individuals’ update rates in any population structure. Our findings provide a unifying framework to understand the interplay between structural heterogeneity, behavioural rhythms, and cooperation.
Integrating social vulnerability into high-resolution global flood risk mapping
Authors: Fox Sean , Agyemang Felix , Hawker Laurence , Neal Jeffrey 
Published: April 2024

Abstract
High-resolution global flood risk maps are increasingly used to inform disaster risk planning and response, particularly in lower income countries with limited data or capacity. However, current approaches do not adequately account for spatial variation in social vulnerability, which is a key determinant of variation in outcomes for exposed populations. Here we integrate annual average exceedance probability estimates from a high-resolution fluvial flood model with gridded population and poverty data to create a global vulnerability-adjusted risk index for flooding (VARI Flood) at 90-meter resolution. The index provides estimates of relative risk within or between countries and changes how we understand the geography of risk by identifying ‘hotspots’ characterised by high population density and high levels of social vulnerability. This approach, which emphasises risks to human well-being, could be used as a complement to traditional population or asset-centred approaches.
A terahertz meta-sensor array for 2D strain mapping
Authors: Lu Xueguang , Zhang Feilong , Zhu Liguo , Peng Shan , Yan Jiazhen , Shi Qiwu , Chen Kefan , Chang Xue , Zhu Hongfu , Zhang Cheng , Huang Wanxia , Cheng Qiang 
Published: April 2024

AbstractLarge-scale stretchable strain sensor arrays capable of mapping two-dimensional strain distributions have gained interest for applications as wearable devices and relating to the Internet of Things. However, existing strain sensor arrays are usually unable to achieve accurate directional recognition and experience a trade-off between high sensing resolution and large area detection. Here, based on classical Mie resonance, we report a flexible meta-sensor array that can detect the in-plane direction and magnitude of preloaded strains by referencing a dynamically transmitted terahertz (THz) signal. By building a one-to-one correspondence between the intrinsic electrical/magnetic dipole resonance frequency and the horizontal/perpendicular tension level, arbitrary strain information across the meta-sensor array is accurately detected and quantified using a THz scanning setup. Particularly, with a simple preparation process of micro template-assisted assembly, this meta-sensor array offers ultrahigh sensor density (~11.1 cm−2) and has been seamlessly extended to a record-breaking size (110 × 130 mm2), demonstrating its promise in real-life applications.
Adaptive expansion of ERVK solo-LTRs is associated with Passeriformes speciation events
Authors: Chen Guangji , Yu Dan , Yang Yu , Li Xiang , Wang Xiaojing , Sun Danyang , Lu Yanlin , Ke Rongqin , Zhang Guojie , Cui Jie , Feng Shaohong 
Published: April 2024

AbstractEndogenous retroviruses (ERVs) are ancient retroviral remnants integrated in host genomes, and commonly deleted through unequal homologous recombination, leaving solitary long terminal repeats (solo-LTRs). This study, analysing the genomes of 362 bird species and their reptilian and mammalian outgroups, reveals an unusually higher level of solo-LTRs formation in birds, indicating evolutionary forces might have purged ERVs during evolution. Strikingly in the order Passeriformes, and especially the parvorder Passerida, endogenous retrovirus K (ERVK) solo-LTRs showed bursts of formation and recurrent accumulations coinciding with speciation events over past 22 million years. Moreover, our results indicate that the ongoing expansion of ERVK solo-LTRs in these bird species, marked by high transcriptional activity of ERVK retroviral genes in reproductive organs, caused variation of solo-LTRs between individual zebra finches. We experimentally demonstrated that cis-regulatory activity of recently evolved ERVK solo-LTRs may significantly increase the expression level of ITGA2 in the brain of zebra finches compared to chickens. These findings suggest that ERVK solo-LTRs expansion may introduce novel genomic sequences acting as cis-regulatory elements and contribute to adaptive evolution. Overall, our results underscore that the residual sequences of ancient retroviruses could influence the adaptive diversification of species by regulating host gene expression.
Controlled condensation by liquid contact-induced adaptations of molecular conformations in self-assembled monolayers
Authors: Bai Guoying , Zhang Haiyan , Gao Dong , Fei Houguo , Guo Cunlan , Ren Mingxia , Liu Yufeng 
Published: April 2024

AbstractSurface condensation control strategies are crucial but commonly require relatively tedious, time-consuming, and expensive techniques for surface-chemical and topographical engineering. Here we report a strategy to alter surface condensation behavior without resorting to any molecule-type or topographical transmutations. After ultrafast contact of liquids with and removal from surfaces, the condensation rate and density of water droplets on the surfaces decrease, the extent of which is positively correlated with the polarity of the liquid and the duration of contact. The liquid contact-induced condensation rate/density decrease (LCICD) can be attributed to the decrease of nucleation site density resulted from the liquid contact-induced adaption of surface molecular conformation. Based on this, we find that LCICD is applicable to various surfaces, on condition that there are flexible segments capable of shielding at least part of nucleation sites through changing the conformation under liquid contact induction. Leveraging the LCICD effect, we achieve erasable information storage on diverse substrates. Furthermore, our strategy holds promise for controlling condensation of other substances since LCICD is not specific to the water condensation process.
Neural signatures of indirect pathway activity during subthalamic stimulation in Parkinson’s disease
Authors: Steiner Leon A. , Crompton David , Sumarac Srdjan , Vetkas Artur , Germann Jürgen , Scherer Maximilian , Justich Maria , Boutet Alexandre , Popovic Milos R. , Hodaie Mojgan , Kalia Suneil K. , Fasano Alfonso , Hutchison WD William D. , Lozano Andres M. , Lankarany Milad , Kühn Andrea A. , Milosevic Luka 
Published: April 2024

AbstractDeep brain stimulation (DBS) of the subthalamic nucleus (STN) produces an electrophysiological signature called evoked resonant neural activity (ERNA); a high-frequency oscillation that has been linked to treatment efficacy. However, the single-neuron and synaptic bases of ERNA are unsubstantiated. This study proposes that ERNA is a subcortical neuronal circuit signature of DBS-mediated engagement of the basal ganglia indirect pathway network. In people with Parkinson’s disease, we: (i) showed that each peak of the ERNA waveform is associated with temporally-locked neuronal inhibition in the STN; (ii) characterized the temporal dynamics of ERNA; (iii) identified a putative mesocircuit architecture, embedded with empirically-derived synaptic dynamics, that is necessary for the emergence of ERNA in silico; (iv) localized ERNA to the dorsal STN in electrophysiological and normative anatomical space; (v) used patient-wise hotspot locations to assess spatial relevance of ERNA with respect to DBS outcome; and (vi) characterized the local fiber activation profile associated with the derived group-level ERNA hotspot.